KR20110026196A - Novel potassium azidoaryltrifluoroborate derivatives and method for producing the same - Google Patents
Novel potassium azidoaryltrifluoroborate derivatives and method for producing the same Download PDFInfo
- Publication number
- KR20110026196A KR20110026196A KR1020090083991A KR20090083991A KR20110026196A KR 20110026196 A KR20110026196 A KR 20110026196A KR 1020090083991 A KR1020090083991 A KR 1020090083991A KR 20090083991 A KR20090083991 A KR 20090083991A KR 20110026196 A KR20110026196 A KR 20110026196A
- Authority
- KR
- South Korea
- Prior art keywords
- potassium
- group
- derivative
- azidoaryl
- trifluoroborate
- Prior art date
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- 239000011591 potassium Substances 0.000 title claims abstract description 78
- 229910052700 potassium Inorganic materials 0.000 title claims abstract description 78
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 title claims abstract description 77
- 238000004519 manufacturing process Methods 0.000 title claims description 16
- -1 copper halide Chemical class 0.000 claims abstract description 82
- 238000006243 chemical reaction Methods 0.000 claims abstract description 48
- 238000000034 method Methods 0.000 claims abstract description 24
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 claims abstract description 20
- 150000001412 amines Chemical class 0.000 claims abstract description 14
- 239000003446 ligand Substances 0.000 claims abstract description 13
- 229910017053 inorganic salt Inorganic materials 0.000 claims abstract description 10
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims abstract description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical group [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims abstract description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims abstract description 5
- 239000000126 substance Substances 0.000 claims abstract description 5
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims abstract description 4
- 229910000024 caesium carbonate Inorganic materials 0.000 claims abstract description 4
- 229910000019 calcium carbonate Inorganic materials 0.000 claims abstract description 3
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 claims abstract description 3
- 238000002156 mixing Methods 0.000 claims abstract description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 claims abstract description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 28
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 26
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical class FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 claims description 13
- 150000004820 halides Chemical class 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 11
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 9
- 239000003054 catalyst Substances 0.000 claims description 8
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 8
- KVKFRMCSXWQSNT-UHFFFAOYSA-N n,n'-dimethylethane-1,2-diamine Chemical compound CNCCNC KVKFRMCSXWQSNT-UHFFFAOYSA-N 0.000 claims description 8
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 claims description 5
- 125000004104 aryloxy group Chemical group 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 230000035484 reaction time Effects 0.000 claims description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 4
- 235000010290 biphenyl Nutrition 0.000 claims description 4
- 239000004305 biphenyl Substances 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000002971 oxazolyl group Chemical group 0.000 claims description 4
- HVVNJUAVDAZWCB-UHFFFAOYSA-N prolinol Chemical compound OCC1CCCN1 HVVNJUAVDAZWCB-UHFFFAOYSA-N 0.000 claims description 4
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 125000004306 triazinyl group Chemical group 0.000 claims description 4
- JRHPOFJADXHYBR-UHFFFAOYSA-N 1-n,2-n-dimethylcyclohexane-1,2-diamine Chemical compound CNC1CCCCC1NC JRHPOFJADXHYBR-UHFFFAOYSA-N 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 claims description 2
- 239000011630 iodine Substances 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 150000001642 boronic acid derivatives Chemical class 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 239000010949 copper Substances 0.000 abstract description 3
- 229910052802 copper Inorganic materials 0.000 abstract description 2
- CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 43
- 238000003786 synthesis reaction Methods 0.000 description 30
- 150000001875 compounds Chemical class 0.000 description 29
- 230000015572 biosynthetic process Effects 0.000 description 26
- 238000000746 purification Methods 0.000 description 14
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 13
- 238000002000 high resolution fast-atom bombardment mass spectrometry Methods 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 9
- WUUHFRRPHJEEKV-UHFFFAOYSA-N tripotassium borate Chemical compound [K+].[K+].[K+].[O-]B([O-])[O-] WUUHFRRPHJEEKV-UHFFFAOYSA-N 0.000 description 9
- IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 description 8
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 6
- 125000000217 alkyl group Chemical group 0.000 description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 4
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- 229930014626 natural product Natural products 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000000975 bioactive effect Effects 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000012433 hydrogen halide Substances 0.000 description 3
- 229910000039 hydrogen halide Inorganic materials 0.000 description 3
- 230000009257 reactivity Effects 0.000 description 3
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 2
- 238000006161 Suzuki-Miyaura coupling reaction Methods 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 150000001502 aryl halides Chemical class 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 239000010948 rhodium Substances 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 238000006257 total synthesis reaction Methods 0.000 description 2
- IBFAGZLTLIKNMS-UHFFFAOYSA-N (2,5-dimethylphenyl) 2,2,2-trifluoroacetate Chemical compound CC1=CC=C(C)C(OC(=O)C(F)(F)F)=C1 IBFAGZLTLIKNMS-UHFFFAOYSA-N 0.000 description 1
- IPWROZUTGADHSU-UHFFFAOYSA-N (4-phenylphenyl) 2,2,2-trifluoroacetate Chemical compound C1=CC(OC(=O)C(F)(F)F)=CC=C1C1=CC=CC=C1 IPWROZUTGADHSU-UHFFFAOYSA-N 0.000 description 1
- VEKWVLWWZITZTK-UHFFFAOYSA-N 1,2-dimethylcyclohexane-1,2-diamine Chemical compound CC1(N)CCCCC1(C)N VEKWVLWWZITZTK-UHFFFAOYSA-N 0.000 description 1
- LHKIPLFQZCQQIG-UHFFFAOYSA-N B1=C(C(=C1F)F)F Chemical compound B1=C(C(=C1F)F)F LHKIPLFQZCQQIG-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 150000004982 aromatic amines Chemical class 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- JNQPQEHGPXDQTA-UHFFFAOYSA-N boric acid;2,2,2-trifluoroacetic acid Chemical compound OB(O)O.OC(=O)C(F)(F)F JNQPQEHGPXDQTA-UHFFFAOYSA-N 0.000 description 1
- 150000001639 boron compounds Chemical class 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006352 cycloaddition reaction Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- OCIFZBONRSADGH-UHFFFAOYSA-N fluorooxyboronic acid Chemical compound OB(O)OF OCIFZBONRSADGH-UHFFFAOYSA-N 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000002734 organomagnesium group Chemical group 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- DVCMYAIUSOSIQP-UHFFFAOYSA-N phenyl 2,2,2-trifluoroacetate Chemical compound FC(F)(F)C(=O)OC1=CC=CC=C1 DVCMYAIUSOSIQP-UHFFFAOYSA-N 0.000 description 1
- 238000006552 photochemical reaction Methods 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- PBIMIGNDTBRRPI-UHFFFAOYSA-N trifluoro borate Chemical compound FOB(OF)OF PBIMIGNDTBRRPI-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/027—Organoboranes and organoborohydrides
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
- B01J23/38—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals
- B01J23/40—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals of the platinum group metals
- B01J23/44—Palladium
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
- B01J23/38—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals
- B01J23/54—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals combined with metals, oxides or hydroxides provided for in groups B01J23/02 - B01J23/36
- B01J23/56—Platinum group metals
- B01J23/60—Platinum group metals with zinc, cadmium or mercury
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C247/00—Compounds containing azido groups
- C07C247/16—Compounds containing azido groups with azido groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
Abstract
Description
본 발명은 신규한 포타슘 아지도아릴트리플루오로보레이트 유도체 및 이를 효율적으로 제조할 수 있는 방법에 관한 것이다.The present invention relates to a novel potassium azidoaryltrifluoroborate derivative and a method for efficiently preparing the same.
아자이드기(azide group)은 유기화학에서 환원반응을 통한 아민기(amine group) 도입과 광화학반응(photochemical reaction) 및 고리첨가반응(cycloaddition reaction)에 널리 사용되는 중요한 작용기이므로 이를 포함하는 화합물에 대한 관심이 점차 증대되고 있다. Azide groups are important functional groups widely used in organic chemistry for introduction of amine groups through reduction reactions, photochemical reactions and cycloaddition reactions. Interest is growing.
특히, 아릴아자이드(arylazide) 유도체는 생리활성 천연물, 의약품 중간체 및 유기합성 또는 신소재 개발연구에 있어 그 유용성이 많지만 개발 및 판매 되는 아릴아자이드 유도체의 종류는 매우 적은 편이다. 따라서, 이러한 아릴아자이드를 활용한 유기합성 연구에 많은 어려움이 있다. 지금까지 알려진 일반적인 아릴아자 이드의 제조방법으로는, 아릴 아민을 출발 물질로 하여 산성조건 하에서 NaNO2와 NaN3를 차례로 반응시켜 제조하거나(반응식 1-(1)), 아릴 할라이드에 NaN3와 CuI/아민 리간드를 반응시켜 제조하며(반응식 1-(2)), 또는 아릴 붕소산 화합물에 NaN3와 팔라듐/수은 또는 구리 촉매를 사용하여 제조하는 방법(반응식 1-(3))이 알려져 있다. 이러한 방법들을 간단히 정리하면, 다음과 같다.In particular, arylazide derivatives are useful in the study of bioactive natural products, pharmaceutical intermediates, and organic synthesis or new material development, but there are very few kinds of arylazide derivatives developed and sold. Therefore, there are many difficulties in the study of organic synthesis using such aryl azide. As a general method for preparing an aryl azide, it is prepared by sequentially reacting NaNO 2 with NaN 3 under acidic conditions using aryl amine as a starting material (Scheme 1- (1)), or NaN 3 and CuI in an aryl halide. It is known to prepare by reacting an amine ligand (Scheme 1- (2)) or by using NaN 3 and palladium / mercury or a copper catalyst in an aryl boronic acid compound (Scheme 1- (3)). To summarize these methods,
[반응식 1-(1)]Scheme 1- (1)
[반응식 1-(2)]Scheme 1- (2)
[반응식 1-(3)]Scheme 1- (3)
그러나, 상기의 제조방법들은 아릴 치환기(R)의 종류에 따라 반응이 제한적 이며, 일반적인 유기화학 반응에서 아자이드기(azide group)는 부반응을 일으키기 쉽고, 고온에서 불안정한 단점이 있다. 그러므로, 아자이드기를 포함한 화합물의 다단계 화학반응은, 아자이드기의 변화나 변형이 쉽게 일어나므로 수행하기 매우 어려운 문제점이 있다.However, in the above-described manufacturing methods, the reaction is limited depending on the type of the aryl substituent (R), and in general organic chemical reactions, azide groups tend to cause side reactions and have unstable high temperatures. Therefore, the multistage chemical reaction of the compound containing an azide group has a problem that is very difficult to perform because the change or modification of the azide group easily occurs.
한편, 유기 화학 분야에서는 팔라듐(Pd) 촉매를 이용한 탄소-탄소 결합 방법이 다양한 생리활성물질 및 천연물의 전합성 연구에 널리 사용되고 있다. 특히, 일본의 스즈키(Suzuki) 교수와 미야우라(Miyaura) 교수에 의해 발견된 붕소(boron) 화합물을 이용한 탄소-탄소 결합반응은, 기존에 이용된 유기아연(organozinc), 유기주석(organotin) 또는 유기마그네슘(Grignard reagent) 화합물에 비해 독성이 낮아 자연 친화성이 큰 화합물로써 인체에 덜 위험하다는 장점이 있다. 또한, 반응조건에 물을 사용하는 등 기존에 사용되었던 반응보다 안정적이며, 다양한 분야(천연물 전합성, 의약화학, 고분자합성 등)에서 적용이 용이하다는 장점을 갖고 있다.Meanwhile, in the organic chemistry field, a carbon-carbon bonding method using a palladium (Pd) catalyst has been widely used for the study of the synthesis of various bioactive substances and natural products. Particularly, the carbon-carbon coupling reaction using boron compounds discovered by Suzuki and Miyaura, Japan, can be used for organozinc, organotin, or Compared with organomagnesium (Grignard reagent) compound, it is less toxic and has a high natural affinity compound, which is less dangerous to the human body. In addition, it is more stable than conventional reactions such as using water in the reaction conditions, and has the advantage that it is easy to apply in various fields (natural synthesis, medicinal chemistry, polymer synthesis, etc.).
특히, 최근에는 스즈키-미야우라 탄소-탄소 결합반응에 포타슘 오가노트리플루오로보레이트(potassium organotrifluoroborate)의 사용이 점차 증가하는 추세이다. 이는 포타슘 오가노트리플루오로보레이트가 기존에 주로 사용되어온 유기붕소산(organoboronic acid) 또는 유기붕소에스터(organoboronate ester)에 비하여 공기와 수분에 안정하고, 취급이 편한 고체상으로써 정량적인 반응이 가능하기 때문이다. 제조방법에 있어서도, 유기붕소산 또는 유기붕소에스터에 상대적으로 저렴한 포타슘하이드로겐플로라이드(KHF2)를 첨가함으로써 용이하게 제조할 수 있다는 장점이 있다. 또한, 반응성 측면에서도 기존의 유기붕소산 또는 유기붕소에스터와 커다란 차이가 없으므로 포타슘 오가노트리플루오로보레이트를 이용한 탄소-탄소 결합반응은 앞으로 폭넓은 분야에서 다양하게 활용될 수 있을 것으로 보인다.In particular, recently, the use of potassium organotrifluoroborate in the Suzuki-Miyaura carbon-carbon coupling reaction is gradually increasing. This is because potassium organotrifluoroborate is more stable in air and moisture than organic organoboronic acid or organoboronate ester, which has been used mainly, and thus can be quantitatively reacted. to be. Also in the manufacturing method, there is an advantage that it can be easily produced by adding relatively low potassium hydrogengen fluoride (KHF 2 ) to organoboronic acid or organoboron ester. In addition, the carbon-carbon coupling reaction using potassium organotrifluoroborate is expected to be widely used in a wide range of fields since there is no significant difference from the existing organoboronic acid or organoboron ester in terms of reactivity.
따라서, 아자이드기를 포함하는 포타슘 아지도아릴트리플루오로보레이트 유도체의 개발은, 파라듐 촉매를 사용하는 탄소-탄소 결합반응을 통해 편리하고, 경제적인 방법으로 다양한 종류의 오가노아자이드(organoazide) 화합물을 제조할 수 있는 매우 유용한 화합물을 제공하는 것이다.Accordingly, the development of potassium azidoaryltrifluoroborate derivatives containing azide groups can be carried out in a convenient and economical way through a carbon-carbon bond reaction using a palladium catalyst in various kinds of organoazide compounds. It is to provide a very useful compound that can be prepared.
본 발명은 과거로부터 요청되어 온 기술적 과제를 해결하는 것을 목적으로 한다. 구체적으로, 본 발명의 일실시예에 따른 목적은 다양한 종류의 신규한 포타슘 아지도아릴트리플루오로보레이트 유도체를 제공하는 것이다.The present invention aims to solve the technical problem that has been requested from the past. Specifically, an object according to an embodiment of the present invention is to provide a variety of novel potassium azidoaryltrifluoroborate derivatives.
본 발명의 또 다른 일실시예에 따른 목적은 포타슘 아지도아릴트리플루오로보레이트 유도체를 효율적으로 제조할 수 있는 방법을 제공하는 것이다.An object according to another embodiment of the present invention is to provide a method for efficiently preparing a potassium azidoaryltrifluoroborate derivative.
본 발명은 신규한 포타슘 아지도아릴트리플루오로보레이트 유도체 및 그 제조방법을 제공한다.The present invention provides a novel potassium azidoaryltrifluoroborate derivative and its preparation method.
본 발명에 따른 신규한 포타슘 아지도아릴트리플루오로보레이트 유도체로부터 다양한 종류의 신규 아릴아자이드 화합물을 손쉽게 제조할 수 있으며, 유기합성 반응과 의약품 제조 및 생리활성 천연물의 전합성 분야에서 다양하게 활용 가능하다.Various kinds of novel aryl azide compounds can be easily prepared from the novel potassium azidoaryltrifluoroborate derivatives according to the present invention, and can be variously used in the field of organic synthesis reaction, pharmaceutical preparation, and total synthesis of bioactive natural products. Do.
또한, 본 발명에 따른 제조방법에 따르면, 안정한 포타슘 아지도아릴트리플루오로보레이트 유도체를 단일 반응으로 제조할 수 있는 바, 제조과정이 매우 빠르고, 편리하며 효율적이다.In addition, according to the production method according to the present invention, a stable potassium azidoaryl trifluoroborate derivative can be prepared in a single reaction, the production process is very fast, convenient and efficient.
본 발명은 신규한 포타슘 아지도아릴트리플루오로보레이트 유도체에 대한 것이다. 일실시예에서, 본 발명에 따른 포타슘 아지도아릴트리플루오로보레이트 유도체는 하기 화학식 1의 구조를 갖는다:The present invention is directed to a novel potassium azidoaryltrifluoroborate derivative. In one embodiment, the potassium azidoaryltrifluoroborate derivative according to the present invention has the structure of Formula 1:
[화학식 1][Formula 1]
상기 화학식 1에서, In Chemical Formula 1,
Ar은 페닐 (
R1은 C1-C4 알킬기, C1-C6 알릴기, C1-C4 알킬옥시기, C1-C4 알킬티오옥시기, C6-C12 아릴옥시기, 하나 이상의 할로겐이 치환된 C1-C4 알킬기, 하나 이상의 할로겐이 치환된 C1-C4 알킬옥시기, 니트로기(-NO2), 시안기(-CN), 불소, 염소, 브롬, 요오드, 및 수소로 구성된 군으로부터 선택되며,R 1 is a C 1 -C 4 alkyl group, C 1 -C 6 allyl group, C 1 -C 4 alkyloxy group, C 1 -C 4 alkylthiooxy group, C 6 -C 12 aryloxy group, at least one halogen A substituted C 1 -C 4 alkyl group, at least one halogen substituted C 1 -C 4 alkyloxy group, a nitro group (—NO 2 ), a cyan group (—CN), fluorine, chlorine, bromine, iodine, and hydrogen Selected from the group consisting of,
n은 1 내지 4의 정수이다.n is an integer of 1-4.
본 발명에서 사용된 용어 "C1-C4 알킬기"는, 1 내지 4 개의 탄소 원자를 가지는 직쇄 또는 분지쇄, 치환 또는 비치환의 알킬기를 포함한다. 상기 알킬기의 예로는, 특별히 한정되는 것은 아니며, 메틸, 에틸, 에테닐, 에티닐, n-프로필, 이소프로필, 프로페닐, 이소프로페닐, 프로피닐, n-부틸, 이소부틸, sec-부틸, t-부틸, 부테닐, 이소부테닐, 및 부티닐 등을 포함하며, 보다 구체적으로는 메틸일 수 있다.As used herein, the term “C 1 -C 4 alkyl group” includes straight or branched chain, substituted or unsubstituted alkyl groups having 1 to 4 carbon atoms. Examples of the alkyl group are not particularly limited, and methyl, ethyl, ethenyl, ethynyl, n-propyl, isopropyl, propenyl, isopropenyl, propynyl, n-butyl, isobutyl, sec-butyl, t-butyl, butenyl, isobutenyl, butynyl and the like, more specifically methyl.
용어 "C1-C4 알킬옥시기"는 알킬-O-기를 나타내는 것으로, 상기 알킬은 앞서 정의된 바와 같이 1 내지 4개의 탄소 원자를 가지는 직쇄 또는 분지쇄, 포화 또는 불포화, 치환 또는 비치환 알킬기일 수 있다. 보다 구체적으로는, C1-C4 알킬옥시기는 메톡시일 수 있다. 또한, 치환 알킬기를 포함하는 알킬옥시기는, 불소 치환 메톡시일 수 있고, 구체적으로는 '-OCF3'일 수 있으나, 이에 한정되는 것은 아니다. The term "C 1 -C 4 alkyloxy group" refers to an alkyl-O- group, wherein alkyl is a straight or branched chain, saturated or unsaturated, substituted or unsubstituted alkyl group having 1 to 4 carbon atoms as defined above. Can be. More specifically, C 1 -C 4 The alkyloxy group may be methoxy. In addition, the alkyloxy group including a substituted alkyl group may be fluorine-substituted methoxy, specifically '-OCF 3 ', but is not limited thereto.
용어 "C6-C12 아릴옥시기"는 아릴-O-기를 나타내는 것이다. 상기 아릴은 치환 또는 비치환 C6-C12 방향족 탄화수소를 나타내고, 예를 들어 페닐, 나프틸, 안트라세닐, 페난트레닐 및 플루오레닐 등이 포함되나, 이에 한정되는 것은 아니다. 또한, 용어 "C1-C4 알킬티오옥시기" 는 알킬-S-기를 나타내는 것으로, 상기 알킬은 앞서 정의된 바와 같으나, 이에 한정되는 것은 아니다.The term "C 6 -C 12 aryloxy group" refers to an aryl-O- group. The aryl is substituted or unsubstituted C 6 -C 12 Aromatic hydrocarbons, and examples include, but are not limited to, phenyl, naphthyl, anthracenyl, phenanthrenyl, fluorenyl, and the like. Also, the term "C 1 -C 4 Alkylthiooxy group "refers to an alkyl-S- group, wherein alkyl is as defined above, but is not limited thereto.
일실시예에서, 본 발명에 따른 포타슘 아지도아릴트리플루오로보레이트 유도체는, 특별히 한정되는 것은 아니며, 포타슘 4-아지도페닐트리플루오로보레이트, 포타슘 3-아지도페닐트리플루오로보레이트, 포타슘 2-아지도페닐트리플루오로보레이트, 포타슘 3-아지도-5-메틸페닐트리플루오로보레이트, 포타슘 4-아지도-2,5-디메틸페닐트리플루오로보레이트, 포타슘 3-아지도-5-메톡시페닐트리플루오로보레이트, 포타슘 6-아지도피리딘-2-일트리플루오로보레이트, 6-아지도피리딘-3-일트리플루오로보레이트, 포타슘 6-아지도-2-메틸피리딘-3-일트리플루오로보레이트, 포타슘 6-아지도-5-메틸피리딘-3-일트리플루오로보레이트, 포타슘 4-(4-아지도펜옥시)페닐트리플루오로보레이트, 포타슘 4-아지도나프탈렌-1-일트리플루오로보레이트 및 포타슘 4'-아지도바이페닐-4-일트리플루오로보레이트로 이루어진 군에서 선택된 하나 이상일 수 있다.In one embodiment, the potassium azidoaryltrifluoroborate derivative according to the present invention is not particularly limited, potassium 4-azidophenyltrifluoroborate, potassium 3-azidophenyltrifluoroborate, potassium 2 -Azidophenyltrifluoroborate, potassium 3-azido-5-methylphenyltrifluoroborate, potassium 4-azido-2,5-dimethylphenyltrifluoroborate, potassium 3-azido-5-methoxy Phenyltrifluoroborate, potassium 6-azidopyridin-2-yltrifluoroborate, 6-azidopyridin-3-yltrifluoroborate, potassium 6-azido-2-methylpyridin-3-yltri Fluoroborate, Potassium 6-azido-5-methylpyridin-3-yltrifluoroborate, Potassium 4- (4-azidophenoxy) phenyltrifluoroborate, potassium 4-azidonaphthalen-1-yl Trifluoroborate and Potassium 4'-azidobaipe 4-yl-tree may be at least one selected from the group consisting of fluoro borate.
본 발명에 따른 포타슘 아지도아릴트리플루오로보레이트 유도체는, 팔라듐(Pd) 촉매를 이용한 스즈키-미야우라 탄소-탄소 결합반응(Suzuki-Miyaura carbon-carbon coupling reaction), 로듐(Rh) 촉매를 이용한 부가반응 또는 할로겐 치환반응 등을 통해 다양한 종류의 신규 아릴아자이드 화합물을 손쉽게 제조할 수 있다. 이러한, 포타슘 아지도아릴트리플루오로보레이트 유도체는, 다양한 유기합성 반응과 의약품 제조 및 생리활성 천연물의 전합성에서 요구되는 아릴아자이드 기능기(functional group)의 도입 반응에 널리 이용될 수 있는 반응물질로 활용 가능하다.Potassium azidoaryltrifluoroborate derivatives according to the present invention may be added using a Suzuki-Miyaura carbon-carbon coupling reaction using a palladium (Pd) catalyst and a rhodium (Rh) catalyst. Various kinds of novel aryl azide compounds can be easily prepared through reaction or halogen substitution. These potassium azidoaryltrifluoroborate derivatives are widely used in the reaction of various organic synthesis reactions and the introduction of aryl azide functional groups required for the preparation of pharmaceuticals and the total synthesis of physiologically active natural products. It can be used as.
또한, 본 발명은 포타슘 아지도아릴트리플루오로보레이트 유도체에 대한 제조방법을 제공한다. 일실시예에서, 본 발명에 따른 포타슘 아지도아릴트리플루오로보레이트 유도체는 다음의 반응식 2의 과정을 통해 제조될 수 있다:The present invention also provides a preparation method for the potassium azidoaryltrifluoroborate derivative. In one embodiment, the potassium azidoaryltrifluoroborate derivative according to the present invention may be prepared through the process of Scheme 2:
[반응식 2]Scheme 2
상기 반응식 2에서, In Scheme 2,
Ar은 페닐 (
R1은 C1-C4 알킬기, C1-C6 알릴기, C1-C4 알킬옥시기, C1-C4 알킬티오옥시기, C6-C12 아릴옥시기, 하나 이상의 할로겐이 치환된 C1-C4 알킬기, 하나 이상의 할로겐이 치환된 C1-C4 알킬옥시기, 니트로기(-NO2), 시안기(-CN), 불소, 염소, 브롬, 요오드 및 수소로 구성된 군으로부터 선택되며,R 1 is a C 1 -C 4 alkyl group, C 1 -C 6 allyl group, C 1 -C 4 alkyloxy group, C 1 -C 4 alkylthiooxy group, C 6 -C 12 aryloxy group, at least one halogen A substituted C 1 -C 4 alkyl group, consisting of one or more halogen-substituted C 1 -C 4 alkyloxy groups, a nitro group (-NO 2 ), a cyan group (-CN), fluorine, chlorine, bromine, iodine and hydrogen Selected from the group,
X는 요오드, 브롬 또는 염소이며,X is iodine, bromine or chlorine,
n은 1 내지 4의 정수이다. n is an integer of 1-4.
일실시예에서, 상기 제조방법은, 포타슘 할로아릴트리플루오로보레이트 유도체, 소듐아자이드(NaN3), 커퍼할라이드(CuX), 아민 리간드 및 무기염을 혼합하여 단일공정으로 반응을 진행될 수 있다. 예를 들어, 상기 반응식 2에 나타난 바와 같이, 출발물질인 포타슘 할로아릴트리플루오로보레이트를 용매 상에서 소듐아자이드(NaN3), 커퍼할라이드(CuX), 아민리간드(A) 및 무기염기(B)와 동시에 반응시켜 화학식 1의 포타슘 아지도아릴트리플루오로보레이트를 제조할 수 있다. 상기 용매는, 예를 들어, 디메틸설폭시드(DMSO) 또는 N,N-디메틸포름아미드(DMF) 용매일 수 있다.In one embodiment, the production method, the potassium haloaryltrifluoroborate derivative, sodium azide (NaN 3 ), cupper halide (CuX), the amine ligand and the inorganic salt may be mixed in a single process. For example, as shown in Scheme 2, the starting material potassium haloaryltrifluoroborate was dissolved in sodium azide (NaN 3 ), cupper halide (CuX), amine ligand (A) and inorganic base (B) in a solvent. And simultaneously reacted with potassium azidoaryltrifluoroborate of formula (1). The solvent may be, for example, dimethyl sulfoxide (DMSO) or N , N -dimethylformamide (DMF) solvent.
본 발명에 따른 포타슘 아지도아릴트리플루오로보레이트 유도체의 제조방법에 따르면, 포타슘 할로아릴트리플루오로보레이트 유도체로부터 안정한 포타슘 아지도아릴트리플루오로보레이트 유도체를 단일반응 공정을 통해 제조할 수 있는 바, 제조과정이 매우 빠르고 편리하며, 효율적이다.According to the method for preparing a potassium azidoaryltrifluoroborate derivative according to the present invention, a stable potassium azidoaryltrifluoroborate derivative can be prepared from a potassium haloaryltrifluoroborate derivative through a single reaction process. The manufacturing process is very fast, convenient and efficient.
본 발명에 따른 제조방법으로 제조된 포타슘 아지도아릴트리플루오로보레이트 유도체는 상기 화학식 1과 같이 표현될 수 있다. 보다 구체적으로는, 상기 포타슘 아지도아릴트리플루오로보레이트 유도체는, 포타슘 4-아지도페닐트리플루오로보레이트, 포타슘 3-아지도페닐트리플루오로보레이트, 포타슘 2-아지도페닐트리플루오로보레이트, 포타슘 3-아지도-5-메틸페닐트리플루오로보레이트, 포타슘 4-아지도-2,5-디메틸페닐트리플루오로보레이트, 포타슘 3-아지도-5-메톡시페닐트리플루오로보레이트, 포타슘 6-아지도피리딘-2-일트리플루오로보레이트, 6-아지도피리딘-3-일트리플루오로보레이트, 포타슘 6-아지도-2-메틸피리딘-3-일트리플루오로보레이트, 포타슘 6-아지도-5-메틸피리딘-3-일트리플루오로보레이트, 포타슘 4-(4-아지도펜옥시)페닐트리플루오로보레이트, 포타슘 4-아지도나프탈렌-1-일트리플루오로보레이트 및 포타슘 4'-아지도바이페닐-4-일트리플루오로보레이트로 이루어진 군에서 선택된 하나 이상일 수 있으나, 이에 제한되는 것은 아니다.The potassium azidoaryl trifluoroborate derivative prepared by the preparation method according to the present invention may be represented by Chemical Formula 1. More specifically, the potassium azidoaryltrifluoroborate derivatives include potassium 4-azidophenyltrifluoroborate, potassium 3-azidophenyltrifluoroborate, potassium 2-azidophenyltrifluoroborate, Potassium 3-azido-5-methylphenyltrifluoroborate, potassium 4-azido-2,5-dimethylphenyltrifluoroborate, potassium 3-azido-5-methoxyphenyltrifluoroborate, potassium 6- Azidopyridin-2-yltrifluoroborate, 6-azidopyridin-3-yltrifluoroborate, potassium 6-azido-2-methylpyridin-3-yltrifluoroborate, potassium 6-azido -5-methylpyridin-3-yltrifluoroborate, potassium 4- (4-azidophenoxy) phenyltrifluoroborate, potassium 4-azidonaphthalen-1-yltrifluoroborate and potassium 4'- Azidobiphenyl-4-yltrifluoroborate It is at least one selected from the group true, but is not limited to this.
이하, 본 발명에 따른 포타슘 아지도아릴트리플루오로보레이트 유도체의 제조방법에 대하여 보다 구체적으로 설명한다. Hereinafter, a method for preparing the potassium azidoaryl trifluoroborate derivative according to the present invention will be described in more detail.
화학식 1의 화합물은, 예를 들어, 반응식 2의 출발물질인 포타슘 할로아릴트리플루오로보레이트와 소듐아자이드(NaN3), 커퍼할라이드(CuX), 아민류 리간드 및 무기염을 용매에 동시에 혼합하여 반응시킨 후, 용매를 제거하고 정제하여 제조할 수 있다.The compound of Formula 1 is, for example, reacted by simultaneously mixing potassium haloaryltrifluoroborate, sodium azide (NaN 3 ), cupper halide (CuX), amine ligand and inorganic salt as starting materials of Scheme 2 After the removal, the solvent may be removed and purified.
일실시예에서, 상기 제조방법에서 사용되는 소듐아자이드(NaN3)의 함량은, 포타슘 할로아릴트리플루오로보레이트 유도체에 대하여, 통상 1.0~3.0 당량, 보다 구체적으로는 1.0~1.5 당량일 수 있다. 상기 소듐아자이드의 함량범위는, 포타슘 할로아릴트리플루오로보레이트 유도체와의 반응효율을 고려한 것이다. 소듐아자이드의 함량이 1.0 당량 미만인 경우에는, 미반응 포타슘 할로아릴트리플루오로보레이트 유도체가 잔류될 수 있고, 3.0 당량 초과시에는 소듐아자이드의 함량 과다로 인해 효율성이 저하된다. In one embodiment, the content of sodium azide (NaN 3 ) used in the production method may be 1.0 to 3.0 equivalents, more specifically 1.0 to 1.5 equivalents relative to the potassium haloaryltrifluoroborate derivative . The content range of the sodium azide is to consider the reaction efficiency with potassium haloaryltrifluoroborate derivative. If the content of sodium azide is less than 1.0 equivalent, unreacted potassium haloaryltrifluoroborate derivative may remain, and if it exceeds 3.0 equivalents, the efficiency decreases due to excessive content of sodium azide.
또한, 커퍼할라이드(CuX)의 예로는, 커퍼클로라이드(CuCl), 커퍼브로마이드(CuBr) 및 커퍼아이오다이드(CuI) 등을 포함한다. 커퍼할라이드의 함량은, 포타슘 할로아릴트리플루오로보레이트 유도체에 대하여, 통상 0.05~0.3 당량, 보다 구체적으로는 0.05~0.15 당량일 수 있다. 커퍼할라이드는 반응을 촉진하기 위한 촉매로 사용되며, 상기 커퍼할라이드의 함량이 0.05 당량보다 작으면 반응을 충분히 촉진하지 못하며, 0.3 당량보다 많아지면 촉매 첨가로 인한 효율성이 저하된다.In addition, examples of the cupper halide (CuX) include cupper chloride (CuCl), cupper bromide (CuBr), cupper iodide (CuI), and the like. The content of the cupper halide may be 0.05 to 0.3 equivalents, more specifically 0.05 to 0.15 equivalents, relative to the potassium haloaryltrifluoroborate derivative. The cupper halide is used as a catalyst for promoting the reaction. If the content of the cupper halide is less than 0.05 equivalents, the cupper halide does not sufficiently promote the reaction.
또 다른 일실시예에서, 아민 리간드는, 피롤리딘(
무기염으로는, 예를 들어, 탄산나트륨(Na2CO3), 탄산칼륨(K2CO3), 탄산세슘(Cs2CO3), 탄산마그네슘(MgCO3) 및 탄산칼슘(CaCO3)으로 구성된 군으로부터 선택되는 하나 이상이 사용될 수 있으며, 보다 구체적으로는 탄산칼륨 또는 탄산세슘일 수 있다. 무기염의 함량은, 포타슘 할로아릴트리플루오로보레이트 유도체에 대하 여, 통상 1.0~3.0 당량, 보다 구체적으로는 1.0~2.0 당량일 수 있다. 사용되는 무기염은 반응 중 생성되는 할로겐화수소(HX)를 중화시켜 제거함으로써, 할로겐화수소에 의한 반응성 저해를 막는 효과상의 이점이 인정된다. 또한, 무기염의 함량이 1.0 당량 미만인 경우에는 생성되는 할로겐화수소를 효과적으로 제거하지 못해 반응성이 저해되고, 3.0 당량 초과시에는 반응물의 높은 염기성으로 인한 반응물의 분해가 일어나 수율이 낮아질 수 있다. Examples of the inorganic salts include sodium carbonate (Na 2 CO 3 ), potassium carbonate (K 2 CO 3 ), cesium carbonate (Cs 2 CO 3 ), magnesium carbonate (MgCO 3 ) and calcium carbonate (CaCO 3 ). One or more selected from the group can be used, more specifically potassium carbonate or cesium carbonate. The content of the inorganic salt may be usually 1.0 to 3.0 equivalents, more specifically 1.0 to 2.0 equivalents, relative to the potassium haloaryltrifluoroborate derivative. The inorganic salt used is neutralized and removed by the hydrogen halide (HX) produced | generated during reaction, and the effect advantage to prevent the reactivity inhibition by hydrogen halide is recognized. In addition, when the content of the inorganic salt is less than 1.0 equivalent, the generated hydrogen halide may not be effectively removed, thereby inhibiting reactivity, and when the amount is more than 3.0 equivalent, decomposition of the reactant may occur due to the high basicity of the reactant, thereby lowering the yield.
상기 반응에 사용되는 용매로는, 예를 들어, 디메틸설폭시드(DMSO), N,N-디메틸포름아미드(DMF)의 단일용매, 또는 디메틸설폭시드와 N,N-디메틸포름아미드의 혼합용매가 사용될 수 있다.Examples of the solvent used in the reaction include dimethyl sulfoxide (DMSO), a single solvent of N , N -dimethylformamide (DMF), or a mixed solvent of dimethyl sulfoxide and N , N -dimethylformamide. Can be used.
상기 반응이 수행되는 온도는, 출발물질로 사용되는 포타슘 할로아릴트리플루오로보레이트 유도체와 용매(DMSO 또는 DMF)에 따라 달라질 수 있으나, 통상적으로 60~120℃ 범위에서 수행되고, 보다 구체적으로는 80~100℃ 범위일 수 있다. 반응온도가 60℃보다 낮으면 반응속도가 저하될 수 있다. 또한, 아자이드기(azide group)는 고온에서 불안정하기 때문에, 반응온도가 120℃를 초과하게 되면 아자이드기의 변화나 변형이 일어날 수 있다. The temperature at which the reaction is carried out may vary depending on the potassium haloaryltrifluoroborate derivative and the solvent (DMSO or DMF) used as a starting material, but is usually performed in the range of 60 to 120 ° C., more specifically 80 It may range from ~ 100 ℃. If the reaction temperature is lower than 60 ℃ may reduce the reaction rate. In addition, since the azide group is unstable at a high temperature, when the reaction temperature exceeds 120 ° C., the azide group may be changed or deformed.
반응시간은, 통상적으로 30 분~1 일이며, 보다 구체적으로는 30 분~12 시간일 수 있다. 반응시간이 30 분 미만인 경우에는 반응이 충분히 진행되지 못할 수 있고, 반응시간이 1 일을 넘게 되면 화학식 1의 포타슘 아지도아릴트리플루오로보레이트 유도체의 수율이 더 이상 높아지지 않게 된다. The reaction time is usually 30 minutes to 1 day, and more specifically 30 minutes to 12 hours. When the reaction time is less than 30 minutes, the reaction may not proceed sufficiently, and when the reaction time exceeds 1 day, the yield of the potassium azidoaryl trifluoroborate derivative of Formula 1 is no longer increased.
이하, 실시예를 통해 본 발명을 더욱 상술하지만, 하기 실시예는 본 발명을 예시하기 위한 것이며, 본 발명의 범주가 이들만으로 한정되는 것은 아니다.Hereinafter, the present invention will be described in more detail with reference to Examples, but the following Examples are provided to illustrate the present invention, and the scope of the present invention is not limited thereto.
[실시예 1] 포타슘 4- 아지도페닐트리플루오로보레이트의 합성 [Example 1] Synthesis of potassium borate to the 4-O-trifluoromethyl-phenyl map
포타슘 4-아이오도페닐트리플루오로보레이트 310 mg (1.0 mmol), NaN3 68.3 mg (1.05 mmol), CuI 19.1 mg (10 mol %), CsCO3 326 mg (1.0 mmol), N,N'-디메틸에틸렌디아민 17.6 mg (20 mol %)을 디메틸설폭시드(DMSO) 4 mL에 녹이고, 90℃에서 반응시켰다. 반응 1시간 후, 감압 증류하여 용매를 완전히 제거하였다. 잔류물을 무수 아세톤 6 mL에 녹인 뒤, 셀라이트를 사용하여 아세톤에 녹지 않은 염을 제거하였다. 여과된 아세톤 용매를 농축하고 남은 잔류물에 디에틸에테르 (Et2O) 5 mL를 부가하여 결정을 얻었다. 얻어진 결정을 여과 후, 건조하여 표제화합물 212 mg (수율 = 94%)을 얻었다.Potassium 4-iodophenyltrifluoroborate 310 mg (1.0 mmol), NaN 3 68.3 mg (1.05 mmol), CuI 19.1 mg (10 mol%), CsCO 3 326 mg (1.0 mmol), N , N' -dimethyl 17.6 mg (20 mol%) of ethylenediamine was dissolved in 4 mL of dimethylsulfoxide (DMSO) and reacted at 90 ° C. After 1 hour of reaction, the solvent was distilled off under reduced pressure. The residue was taken up in 6 mL of anhydrous acetone and then celite was used to remove salts insoluble in acetone. The filtered acetone solvent was concentrated and 5 mL of diethyl ether (Et 2 O) was added to the remaining residue to obtain crystals. The obtained crystals were filtered and dried to give 212 mg (yield = 94%) of the title compound.
1H NMR (500 MHz, Acetone-d6) δ 7.51 (d, 2H, J = 8.0 Hz), 6.84 (d, 2H, J = 7.5 Hz).; 13C NMR (126 MHz, Acetone-d6) δ 136.2, 133.1, 116.8.; 19F NMR (376 MHz, Acetone-d6) δ -141.4.; 11B NMR (128 MHz, Acetone-d6) δ 3.36.; FT-IR (KBr): 3031, 2122, 2084, 1710, 1599, 1361, 1287, 1222, 963, 927, 820 cm-1.; HRFABMS: m/z calcd for C6H4BF3N3 [M-K+]- 186.0450, found 186.0450. 1 H NMR (500 MHz, Acetone-d 6 ) δ 7.51 (d, 2H, J = 8.0 Hz), 6.84 (d, 2H, J = 7.5 Hz) .; 13 C NMR (126 MHz, Acetone-d 6 ) δ 136.2, 133.1, 116.8 .; 19 F NMR (376 MHz, Acetone-d 6 ) δ −141.4 .; 11 B NMR (128 MHz, Acetone-d6) δ 3.36 .; FT-IR (KBr): 3031, 2122, 2084, 1710, 1599, 1361, 1287, 1222, 963, 927, 820 cm −1 .; HRFABMS: m / z calcd for C 6 H 4 BF 3 N 3 [M-K < + >] - 186.0450, found 186.0450.
[실시예 2] 포타슘 4- 아지도페닐트리플루오로보레이트의 합성 Example 2 Synthesis of potassium borate to the 4-O-trifluoromethyl-phenyl map
CuI를 CuBr 14.4 mg (10 mol %)으로 대체하여 사용한 것을 제외하고는, 상기 실시예 1과 동일한 방법으로 40 분 반응 후, 정제하여 표제화합물 214 mg (수율 = 95%)을 얻었다.40 minutes of reaction was carried out in the same manner as in Example 1, except that CuI was replaced with 14.4 mg (10 mol%) of CuBr, to obtain 214 mg (yield = 95%) of the title compound.
[실시예 3] 포타슘 4- 아지도페닐트리플루오로보레이트의 합성 [Example 3] Synthesis of borate with potassium 4-O-trifluoromethyl-phenyl map
N,N'-디메틸에틸렌디아민을 피롤리딘 14.2 mg (20 mol %)으로 대체하여 사용한 것을 제외하고는, 상기 실시예 1과 동일한 방법으로 24 시간 반응 후, 정제하여 표제화합물 149 mg (수율 = 66%)을 얻었다.Except for using N , N' -dimethylethylenediamine with 14.2 mg (20 mol%) of pyrrolidine, the reaction was carried out in the same manner as in Example 1 after 24 hours, and purified to give 149 mg of the title compound (yield = 66%).
[실시예 4] 포타슘 4- 아지도페닐트리플루오로보레이트의 합성 Example 4 Synthesis of potassium borate to the 4-O-trifluoromethyl-phenyl map
N,N'-디메틸에틸렌디아민을 프롤린 23.0 mg (20 mol %)으로 대체하여 사용한 것을 제외하고는, 상기 실시예 1과 동일한 방법으로 5 시간 반응 후, 정제하여 표제화합물 209 mg (수율 = 93%)을 얻었다.Except for using N , N' -dimethylethylenediamine with 23.0 mg (20 mol%) of proline, the reaction was carried out for 5 hours in the same manner as in Example 1, and purified to give 209 mg of the title compound (yield = 93% )
[실시예 5] 포타슘 4- 아지도페닐트리플루오로보레이트의 합성 [Example 5] Synthesis of potassium borate to the 4-O-trifluoromethyl-phenyl map
N,N'-디메틸에틸렌디아민을 2-피롤리딘메탄올 20.2 mg (20 mol %)으로 대체하여 사용한 것을 제외하고는, 상기 실시예 1과 동일한 방법으로 16 시간 반응 후, 정제하여 표제화합물 212 mg (수율 = 94%)을 얻었다.Except for using N , N' -dimethylethylenediamine with 20.2 mg (20 mol%) of 2-pyrrolidinemethanol, the reaction was carried out in the same manner as in Example 1 after 16 hours, and purified to give 212 mg of the title compound. (Yield = 94%) was obtained.
[실시예 6] 포타슘 4- 아지도페닐트리플루오로보레이트의 합성 Example 6 Synthesis of borate with potassium 4-O-trifluoromethyl-phenyl map
N,N'-디메틸에틸렌디아민을 피페리딘 17.0 mg (20 mol %)으로 대체하여 사용한 것을 제외하고는, 상기 실시예 1과 동일한 방법으로 24 시간 반응 후, 정제하여 표제화합물 182 mg (수율 = 81%)을 얻었다.Except for using N , N' -dimethylethylenediamine with 17.0 mg (20 mol%) of piperidine, the reaction was carried out in the same manner as in Example 1 after 24 hours, and purified to give 182 mg of the title compound (yield = 81%).
[실시예 7] 포타슘 4- 아지도페닐트리플루오로보레이트의 합성 Example 7 Synthesis of borate with potassium 4-O-trifluoromethyl-phenyl map
N,N'-디메틸에틸렌디아민을 N,N'-디메틸시클로헥산-1,2-디아민 28.5 mg (20 mol %)으로 대체하여 사용한 것을 제외하고는, 상기 실시예 1과 동일한 방법으로 15 시간 반응 후, 정제하여 표제화합물 214 mg (수율 = 95%)을 얻었다. N, N '- dimethyl ethylenediamine-N, N' - and is, 15 hours reaction in the same manner as Example 1 except that by replacing dimethyl-cyclohexane-1,2-diamine 28.5 mg (20 mol%) Then, purification gave 214 mg (yield = 95%) of the title compound.
[실시예 8] 포타슘 4- 아지도페닐트리플루오로보레이트의 합성 [Example 8] Synthesis of borate with potassium 4-O-trifluoromethyl-phenyl map
N,N'-디메틸에틸렌디아민을 N,N,N',N'-테트라메틸에틸렌디아민 23.2 mg (20 mol %)으로 대체하여 사용한 것을 제외하고는, 상기 실시예 1과 동일한 방법으로 24 시간 반응 후, 정제하여 표제화합물 25 mg (수율 = 11%)을 얻었다. N, N '- dimethyl-ethylenediamine N, N, N', N '- tetramethyl-, except that in place of ethylene diamine, 23.2 mg (20 mol%), the 24-hour reaction in the same manner as in Example 1 After purification, 25 mg (yield = 11%) of the title compound were obtained.
[실시예 9] 포타슘 4- 아지도페닐트리플루오로보레이트의 합성 [Example 9] Synthesis of borate with potassium 4-O-trifluoromethyl-phenyl map
용매로 디메틸설폭시드(DMSO)를 N,N-디메틸포름아미드(DMF) 4 mL로 대체하여 사용한 것을 제외하고는, 상기 실시예 1과 동일한 방법으로 2.5 시간 반응 후, 정 제하여 표제화합물 212 mg (수율 = 94%)을 얻었다.Except for using dimethyl sulfoxide (DMSO) in 4 mL of N , N -dimethylformamide (DMF) as a solvent, after 2.5 hours of reaction in the same manner as in Example 1, was purified to 212 mg of the title compound (Yield = 94%) was obtained.
[실시예 10] 포타슘 4- 아지도페닐트리플루오로보레이트의 합성 Example 10 Synthesis of borate with potassium 4-O-trifluoromethyl-phenyl map
포타슘 4-아이오도페닐트리플루오로보레이트를 포타슘 4-브로모페닐트리플루오로보레이트 263 mg (1.0 mmol)로 대체하여 사용한 것을 제외하고는, 상기 실시예 2와 동일한 방법으로 7 시간 반응 후, 정제하여 표제화합물 214 mg (수율 = 95%)을 얻었다.Except for using potassium 4-iodophenyltrifluoroborate with 263 mg (1.0 mmol) of potassium 4-bromophenyltrifluoroborate, after the reaction in the same manner as in Example 2 for 7 hours, purification 214 mg (yield = 95%) of the title compound were obtained.
[실시예 11] 포타슘 3- 아지도페닐트리플루오로보레이트의 합성 Example 11 Synthesis of 3-O with potassium borate map phenyl trifluoroacetate
포타슘 4-아이오도페닐트리플루오로보레이트를 포타슘 3-아이오도페닐트리플루오로보레이트 310 mg (1.0 mmol)로 대체하여 사용한 것을 제외하고는, 상기 실시예 1과 동일한 방법으로 6 시간 반응 후, 정제하여 표제화합물 203 mg (수율 = 90%)을 얻었다.Except for using potassium 4-iodophenyltrifluoroborate with 310 mg (1.0 mmol) of potassium 3-iodophenyltrifluoroborate, purification was carried out after the reaction in the same manner as in Example 1 for 6 hours. 203 mg (yield = 90%) of the title compound were obtained.
1H NMR (500 MHz, Acetone-d 6) δ 7.31 (d, 1H, J = 7.5 Hz), 7.22 (s, 1H), 7.14 (t, 1H, J = 7.5 Hz), 6.73 (m, 1H).; 13C NMR (126 MHz, Acetone-d 6 ) δ 137.3, 128.7, 127.6, 121.7, 115.6.; 19F NMR (376 MHz, Acetone-d 6) δ -142.8.; 11B NMR (128 MHz, Acetone-d 6) δ 3.20.; FT-IR (KBr): 3046, 2127, 2099, 1571, 1414, 1284, 1205, 967, 868, 775, 694 cm-1.; HRFABMS: m/z calcd for C6H4BF3N3 [M-K+]- 186.0450, found 186.0455. 1 H NMR (500 MHz, Acetone- d 6 ) δ 7.31 (d, 1H, J = 7.5 Hz), 7.22 (s, 1H), 7.14 (t, 1H, J = 7.5 Hz), 6.73 (m, 1 H) .; 13 C NMR (126 MHz, Acetone- d 6) δ 137.3, 128.7, 127.6, 121.7, 115.6 .; 19 F NMR (376 MHz, Acetone- d 6) δ -142.8 .; 11 B NMR (128 MHz, Acetone- d 6 ) δ 3.20; FT-IR (KBr): 3046, 2127, 2099, 1571, 1414, 1284, 1205, 967, 868, 775, 694 cm -1 .; HRFABMS: m / z calcd for C 6 H 4 BF 3 N 3 [MK + ] - 186.0450, found 186.0455.
[실시예 12] 포타슘 3- 아지도페닐트리플루오로보레이트의 합성 [Example 12] Synthesis of potassium borate to the 3-O-trifluoromethyl-phenyl map
포타슘 4-아이오도페닐트리플루오로보레이트를 포타슘 3-브로모페닐트리플루오로보레이트 263 mg (1.0 mmol)로 대체하여 사용한 것을 제외하고는, 상기 실시예 1과 동일한 방법으로 6 시간 반응 후, 정제하여 표제화합물 209 mg (수율 = 93%)을 얻었다.Except for using potassium 4-iodophenyltrifluoroborate with 263 mg (1.0 mmol) of potassium 3-bromophenyltrifluoroborate, after the reaction for 6 hours in the same manner as in Example 1, purification 209 mg (yield = 93%) of the title compound were obtained.
[실시예 13] 포타슘 2- 아지도페닐트리플루오로보레이트의 합성 [Example 13] Synthesis of potassium borate to the 2-O-trifluoromethyl-phenyl map
포타슘 4-아이오도페닐트리플루오로보레이트를 포타슘 2-브로모페닐트리플루오로보레이트 263 mg (1.0 mmol)로 대체하여 사용한 것을 제외하고는, 상기 실시예 1과 동일한 방법으로 24 시간 반응 후, 정제하여 표제화합물 164 mg (수율 = 73%)을 얻었다.After reaction for 24 hours in the same manner as in Example 1, except that potassium 4-iodophenyltrifluoroborate was used in place of 263 mg (1.0 mmol) of potassium 2-bromophenyltrifluoroborate, purification was performed. This gave 164 mg (yield = 73%) of the title compound.
1H NMR (500 MHz, Acetone-d 6) δ 7.57 (d, 1H, J = 7.0 Hz), 7.17 (td, 1H, J = 8.0, 2.0 Hz), 6.97 (t, 1H, J = 7.5 Hz), 6.97 (d, 1H, J = 8.5 Hz).; 13C NMR (126 MHz, Acetone-d 6 ) δ 142.0, 134.1, 127.0, 123.4, 117.3.; 19F NMR (376 MHz, Acetone-d 6) δ -138.8.; 11B NMR (128 MHz, Acetone-d 6) δ 2.91.; FT-IR (KBr): 3055, 2119, 1711, 1968, 1438, 1268, 1199, 960, 753 cm-1.; HRFABMS: m/z calcd for C6H4BF3N3 [M-K+]- 186.0450, found 186.0446. 1 H NMR (500 MHz, Acetone- d 6 ) δ 7.57 (d, 1H, J = 7.0 Hz), 7.17 (td, 1H, J = 8.0, 2.0 Hz), 6.97 (t, 1H, J = 7.5 Hz) , 6.97 (d, 1 H, J = 8.5 Hz) .; 13 C NMR (126 MHz, Acetone- d 6) δ 142.0, 134.1, 127.0, 123.4, 117.3 .; 19 F NMR (376 MHz, Acetone- d 6) δ -138.8 .; 11 B NMR (128 MHz, Acetone- d 6 ) δ 2.91 .; FT-IR (KBr): 3055, 2119, 1711, 1968, 1438, 1268, 1199, 960, 753 cm -1 .; HRFABMS: m / z calcd for C 6 H 4 BF 3 N 3 [MK + ] - 186.0450, found 186.0446.
[실시예 14] 포타슘 3- 아지도 -5- 메틸페닐트리플루오로보레이트의 합성 Example 14 Synthesis of 3-azido FIG potassium borate-5-methylphenyl trifluoromethyl
포타슘 4-아이오도페닐트리플루오로보레이트를 포타슘 3-브로모-5-메틸페닐트리플루오로보레이트 277 mg (1.0 mmol)로 대체하여 사용한 것을 제외하고는, 상 기 실시예 1과 동일한 방법으로 8 시간 반응 후, 정제하여 표제화합물 222 mg (수율 = 93%)을 얻었다.8 hours in the same manner as in Example 1, except that potassium 4-iodophenyltrifluoroborate was replaced with 277 mg (1.0 mmol) of potassium 3-bromo-5-methylphenyltrifluoroborate. After the reaction, purification gave 222 mg (yield = 93%) of the title compound.
1H NMR (500 MHz, DMSO-d 6) δ 6.98 (s, 1H), 6.83 (s, 1H), 6.56 (s, 1H), 2.22 (s, 3H).; 13C NMR (126 MHz, DMSO-d 6 ) δ 137.4, 137.2, 129.9, 118.9, 116.8, 21.4.; 19F NMR (376 MHz, Acetone-d 6) δ -142.5.; 11B NMR (128 MHz, Acetone-d 6) δ 3.09.; FT-IR (KBr): 2917, 2102, 1594, 1415, 1301, 1168, 1043, 988, 943, 872, 813, 709 cm-1.;; HRFABMS: m/z calcd for C7H6BF3N3 [M-K+]- 200.0607, found 200.0612. 1 H NMR (500 MHz, DMSO- d 6) δ 6.98 (s, 1H), 6.83 (s, 1H), 6.56 (s, 1H), 2.22 (s, 3H) .; 13 C NMR (126 MHz, DMSO- d 6 ) δ 137.4, 137.2, 129.9, 118.9, 116.8, 21.4 .; 19 F NMR (376 MHz, Acetone- d 6) δ -142.5 .; 11 B NMR (128 MHz, Acetone- d 6) δ 3.09 .; FT-IR (KBr): 2917, 2102, 1594, 1415, 1301, 1168, 1043, 988, 943, 872, 813, 709 cm -1 .; HRFABMS: m / z calcd for C 7 H 6 BF 3 N 3 [MK + ] - 200.0607, found 200.0612.
[실시예 15] 포타슘 4- 아지도 -2,5- 디메틸페닐트리플루오로보레이트의 합성 Example 15 Potassium 4-azido synthesis of borate to 2,5-dimethylphenyl trifluoroacetate
포타슘 4-아이오도페닐트리플루오로보레이트를 포타슘 4-브로모-2,5-디메틸페닐트리플루오로보레이트 291 mg (1.0 mmol)로 대체하여 사용한 것을 제외하고는, 상기 실시예 1과 동일한 방법으로 12 시간 반응 후, 정제하여 표제화합물 228 mg (수율 = 90%)을 얻었다.In the same manner as in Example 1, except that potassium 4-iodophenyltrifluoroborate was replaced with 291 mg (1.0 mmol) of potassium 4-bromo-2,5-dimethylphenyltrifluoroborate. After 12 hours reaction, purification gave 228 mg (yield = 90%) of the title compound.
1H NMR (500 MHz, Acetone-d 6) δ 7.33 (s, 1H), 6.72 (s, 1H), 2.42 (s, 3H), 2.07 (s, 3H).; 13C NMR (126 MHz, Acetone-d 6 ) δ 140.7, 135.2, 133.9, 123.1, 117.4, 20.8, 15.9.; 19F NMR (376 MHz, Acetone-d 6) δ -138.3.; 11B NMR (128 MHz, Acetone-d 6) δ 3.07.; FT-IR (KBr): 2928, 2112, 2093, 1562, 1384, 1291, 1161, 1063, 948, 901, 849 cm-1.; HRFABMS: m/z calcd for C8H8BF3N3 [M-K+]- 214.0763, found 214.0762. 1 H NMR (500 MHz, Acetone- d 6) δ 7.33 (s, 1H), 6.72 (s, 1H), 2.42 (s, 3H), 2.07 (s, 3H) .; 13 C NMR (126 MHz, Acetone- d 6) δ 140.7, 135.2, 133.9, 123.1, 117.4, 20.8, 15.9 .; 19 F NMR (376 MHz, Acetone d 6 ) δ −138.3 .; 11 B NMR (128 MHz, Acetone- d 6) δ 3.07 .; FT-IR (KBr): 2928, 2112, 2093, 1562, 1384, 1291, 1161, 1063, 948, 901, 849 cm −1 .; HRFABMS: m / z calcd for C 8 H 8 BF 3 N 3 [MK + ] - 214.0763, found 214.0762.
[실시예 16] 포타슘 3- 아지도 -5- 메톡시페닐트리플루오로보레이트의 합성 Example 16 Synthesis of 3-azido FIG potassium borate-5-methoxyphenyl trifluoroacetate
포타슘 4-아이오도페닐트리플루오로보레이트를 포타슘 3-브로모-5-메톡시페닐트리플루오로보레이트 293 mg (1.0 mmol)로 대체하여 사용한 것을 제외하고는, 상기 실시예 1과 동일한 방법으로 4 시간 반응 후, 정제하여 표제화합물 235 mg (수율 = 92%)을 얻었다.In the same manner as in Example 1, except that potassium 4-iodophenyltrifluoroborate was replaced with 293 mg (1.0 mmol) of potassium 3-bromo-5-methoxyphenyltrifluoroborate. After time reaction, purification gave 235 mg (yield = 92%) of the title compound.
1H NMR (500 MHz, Acetone-d 6) δ 6.89 (d, 1H, J = 2.5 Hz), 6.84 (d, 1H, J = 2.0 Hz), 6.28 (t, 1H, J = 2.5 Hz), 3.74 (s, 3H).; 13C NMR (126 MHz, Acetone-d 6 ) δ 159.8, 138.4, 114.1, 113.8, 101.9, 54.3.; 19F NMR (376 MHz, Acetone-d 6) δ -142.4.; 11B NMR (128 MHz, Acetone-d 6) δ 3.09.; FT-IR (KBr): 2950, 2103, 1585, 1412, 1298, 1237, 1168, 1027, 820, 762 cm-1.; HRFABMS: m/z calcd for C7H6BF3N3O [M-K+]- 216.0556, found 216.0563. 1 H NMR (500 MHz, Acetone- d 6 ) δ 6.89 (d, 1H, J = 2.5 Hz), 6.84 (d, 1H, J = 2.0 Hz), 6.28 (t, 1H, J = 2.5 Hz), 3.74 (s, 3H) .; 13 C NMR (126 MHz, Acetone- d 6) δ 159.8, 138.4, 114.1, 113.8, 101.9, 54.3 .; 19 F NMR (376 MHz, Acetone- d 6 ) δ −142.4 .; 11 B NMR (128 MHz, Acetone- d 6) δ 3.09 .; FT-IR (KBr): 2950, 2103, 1585, 1412, 1298, 1237, 1168, 1027, 820, 762 cm -1 .; HRFABMS: m / z calcd for C 7 H 6 BF 3 N 3 O [MK + ] - 216.0556, found 216.0563.
[실시예 17] 포타슘 6- 아지도피리딘 -2- 일트리플루오로보레이트의 합성 Example 17 6-O Synthesis of potassium borate to the map-2-yl trifluoroacetate
포타슘 4-아이오도페닐트리플루오로보레이트를 포타슘 6-브로모피리딘-2-일트리플루오로보레이트 264 mg (1.0 mmol)로 대체하여 사용한 것을 제외하고는, 상기 실시예 1과 동일한 방법으로 1 시간 반응 후, 정제하여 표제화합물 222 mg (수율 = 98%)을 얻었다.1 hour in the same manner as in Example 1, except that potassium 4-iodophenyltrifluoroborate was replaced by 264 mg (1.0 mmol) of potassium 6-bromopyridin-2-yltrifluoroborate After the reaction, purification gave 222 mg (yield = 98%) of the title compound.
1H NMR (500 MHz, DMSO-d 6) δ 7.90 (dd, 1H, J = 9.0, 1.0 Hz), 7.64 (dd, 1H, J = 9.0, 6.5 Hz), 7.16 (d, 1H, J = 6.0 Hz).; 13C NMR (126 MHz, DMSO-d 6) δ 148.2, 132.4, 118.6, 112.3.; 19F NMR (376 MHz, DMSO-d 6) δ -142.4.; 11B NMR (128 MHz, DMSO-d 6) δ 1.17.; FT-IR (KBr): 3088, 1623, 1505, 1261, 1176, 1087, 1019, 995, 977, 919, 797 cm-1.; HRFABMS: m/z calcd for C5H3BF3N4 [M-K+]- 187.0403, found 187.0399. 1 H NMR (500 MHz, DMSO- d 6 ) δ 7.90 (dd, 1H, J = 9.0, 1.0 Hz), 7.64 (dd, 1H, J = 9.0, 6.5 Hz), 7.16 (d, 1H, J = 6.0 Hz) .; 13 C NMR (126 MHz, DMSO- d 6) δ 148.2, 132.4, 118.6, 112.3 .; 19 F NMR (376 MHz, DMSO- d 6) δ -142.4 .; 11 B NMR (128 MHz, DMSO- d 6) δ 1.17 .; FT-IR (KBr): 3088, 1623, 1505, 1261, 1176, 1087, 1019, 995, 977, 919, 797 cm −1 .; HRFABMS: m / z calcd for C 5 H 3 BF 3 N 4 [MK + ] - 187.0403, found 187.0399.
[실시예 18] 포타슘 6- 아지도피리딘 -3- 일트리플루오로보레이트의 합성 [Example 18] 6-O Synthesis of potassium borate to the map-3-yl trifluoroacetate
포타슘 4-아이오도페닐트리플루오로보레이트를 포타슘 6-브로모피리딘-3-일트리플루오로보레이트 264 mg (1.0 mmol)로 대체하여 사용한 것을 제외하고는, 상기 실시예 1과 동일한 방법으로 1 시간 반응 후, 정제하여 표제화합물 222 mg (수율 = 98%)을 얻었다.1 hour in the same manner as in Example 1, except that potassium 4-iodophenyltrifluoroborate was replaced with 264 mg (1.0 mmol) of potassium 6-bromopyridin-3-yltrifluoroborate After the reaction, purification gave 222 mg (yield = 98%) of the title compound.
1H NMR (500 MHz, Acetone-d 6) δ 8.65 (s, 1H), 7.85 (d, 1H, J = 8.5 Hz), 7.82 (d, 1H, J = 9.0 Hz).; 13C NMR (126 MHz, Acetone-d 6 ) δ 148.2, 137.7, 124.8, 112.5.; 19F NMR (376 MHz, Acetone-d 6) δ -142.3.; 11B NMR (128 MHz, Acetone-d 6) δ 2.51.; FT-IR (KBr): 3084, 1621, 1499, 1243, 1201, 1098, 1021, 975, 915, 815, 800, 718 cm-1.; HRFABMS: m/z calcd for C5H3BF3N4 [M-K+]- 187.0403, found 187.0404. 1 H NMR (500 MHz, Acetone- d 6) δ 8.65 (s, 1H), 7.85 (d, 1H, J = 8.5 Hz), 7.82 (d, 1H, J = 9.0 Hz) .; 13 C NMR (126 MHz, Acetone- d 6) δ 148.2, 137.7, 124.8, 112.5 .; 19 F NMR (376 MHz, Acetone- d 6) δ -142.3 .; 11 B NMR (128 MHz, Acetone- d 6 ) δ 2.51 .; FT-IR (KBr): 3084, 1621, 1499, 1243, 1201, 1098, 1021, 975, 915, 815, 800, 718 cm -1 .; HRFABMS: m / z calcd for C 5 H 3 BF 3 N 4 [MK + ] - 187.0403, found 187.0404.
[실시예 19] 포타슘 6- 아지도 -2- 메틸피리딘 -3- 일트리플루오로보레이트의 합성 [Example 19] Synthesis of potassium 6-azido-2-methyl-pyridin-3-yl borate trifluoroacetate
포타슘 4-아이오도페닐트리플루오로보레이트를 포타슘 6-브로모-2-메틸피리딘-3-일트리플루오로보레이트 278 mg (1.0 mmol)로 대체하여 사용한 것을 제외하고는, 상기 실시예 1과 동일한 방법으로 3 시간 반응 후, 정제하여 표제화합물 228 mg (수율 = 95%)을 얻었다.Same as Example 1, except that potassium 4-iodophenyltrifluoroborate was replaced by 278 mg (1.0 mmol) of potassium 6-bromo-2-methylpyridin-3-yltrifluoroborate After 3 hours of reaction, the product was purified to yield 228 mg (yield = 95%) of the title compound.
1H NMR (500 MHz, Acetone-d 6) δ 7.92 (d, 1H, J = 8.5 Hz), 7.68 (d, 1H, J = 9.0 Hz), 2.93 (s, 3H).; 13C NMR (126 MHz, Acetone-d 6 ) δ 148.2, 138.0, 136.8, 109.2, 15.6.; 19F NMR (376 MHz, Acetone-d 6) δ -138.7.; 11B NMR (128 MHz, Acetone-d 6) δ 3.16.; FT-IR (KBr): 2921, 2101, 1583, 1433, 1297, 1171, 960, 836, 710 cm-1.; HRFABMS: m/z calcd for C6H5BF3N4 [M-K+]- 201.0559, found 201.0557. 1 H NMR (500 MHz, Acetone- d 6 ) δ 7.92 (d, 1H, J = 8.5 Hz), 7.68 (d, 1H, J = 9.0 Hz), 2.93 (s, 3H) .; 13 C NMR (126 MHz, Acetone- d 6 ) δ 148.2, 138.0, 136.8, 109.2, 15.6 .; 19 F NMR (376 MHz, Acetone d 6 ) δ −138.7 .; 11 B NMR (128 MHz, Acetone- d 6) δ 3.16 .; FT-IR (KBr): 2921, 2101, 1583, 1433, 1297, 1171, 960, 836, 710 cm −1 .; HRFABMS: m / z calcd for C 6 H 5 BF 3 N 4 [MK + ] - 201.0559, found 201.0557.
[실시예 20] 포타슘 6- 아지도 -5- 메틸피리딘 -3- 일트리플루오로보레이트의 합성 [Example 20] Synthesis of potassium 6-azido-borate-5-methylpyridin-3-yl trifluoroacetate
포타슘 4-아이오도페닐트리플루오로보레이트를 포타슘 6-브로모-5-메틸피리딘-3-일트리플루오로보레이트 278 mg (1.0 mmol)로 대체하여 사용한 것을 제외하고는, 상기 실시예 1과 동일한 방법으로 3 시간 반응 후, 정제하여 표제화합물 228 mg (수율 = 95%)을 얻었다.Same as Example 1, except that potassium 4-iodophenyltrifluoroborate was replaced by 278 mg (1.0 mmol) of potassium 6-bromo-5-methylpyridin-3-yltrifluoroborate After 3 hours of reaction, the product was purified to yield 228 mg (yield = 95%) of the title compound.
1H NMR (500 MHz, Acetone-d 6) δ 8.50 (s, 1H), 7.57 (s, 1H), 2.62 (s, 3H).; 13C NMR (126 MHz, Acetone-d 6) δ 148.7, 136.0, 123.0, 122.4, 15.7.; 19F NMR (376 MHz, Acetone-d 6) δ -142.9.; 11B NMR (128 MHz, Acetone-d 6) δ 2.57.; FT-IR (KBr): 3073, 2058, 1613, 1380, 1234, 1204, 1137, 1023, 1004, 973, 889, 871, 771 cm-1.; HRFABMS: m/z calcd for C6H5BF3N4 [M-K+]- 201.0559, found 201.0563. 1 H NMR (500 MHz, Acetone- d 6) δ 8.50 (s, 1H), 7.57 (s, 1H), 2.62 (s, 3H) .; 13 C NMR (126 MHz, Acetone- d 6) δ 148.7, 136.0, 123.0, 122.4, 15.7 .; 19 F NMR (376 MHz, Acetone- d 6 ) δ −142.9 .; 11 B NMR (128 MHz, Acetone- d 6) δ 2.57 .; FT-IR (KBr): 3073, 2058, 1613, 1380, 1234, 1204, 1137, 1023, 1004, 973, 889, 871, 771 cm -1 .; HRFABMS: m / z calcd for C 6 H 5 BF 3 N 4 [MK + ] - 201.0559, found 201.0563.
[실시예 21] 포타슘 4-(4- 아지도펜옥시 ) 페닐트리플루오로보레이트의 합성 Example 21 Potassium 4- (4-O map phenoxy) phenyl Synthesis of borate trifluoroacetate
포타슘 4-아이오도페닐트리플루오로보레이트를 포타슘 4-(4-브로모펜옥시)페닐트리플루오로보레이트 355 mg (1.0 mmol)로 대체하여 사용한 것을 제외하고는, 상기 실시예 1과 동일한 방법으로 6 시간 반응 후, 정제하여 표제화합물 279 mg (수율 = 88%)을 얻었다.In the same manner as in Example 1, except that potassium 4-iodophenyltrifluoroborate was used in place of 355 mg (1.0 mmol) of potassium 4- (4-bromophenoxy) phenyltrifluoroborate. After time reaction, purification gave 279 mg (yield = 88%) of the title compound.
1H NMR (500 MHz, Acetone-d 6) δ 7.49 (d, 1H, J = 8.0 Hz), 6.89 (d, 1H, J = 8.5 Hz), 6.78 (d, 1H, J = 8.0 Hz), 6.63 (d, 1H, J = 9.0 Hz).; 13C NMR (126 MHz, Acetone-d 6 ) δ 155.1, 154.1, 146.7, 132.9, 120.4, 118.4, 1163.8.; 19F NMR (376 MHz, Acetone-d 6) δ -140.4.; 11B NMR (128 MHz, Acetone- d 6) δ 3.63.; FT-IR (KBr): 3363, 3036, 2921, 2120, 1596, 1496, 1211, 958, 828 cm-1.; HRFABMS: m/z calcd for C12H8BF3N3O [M-K+]- 278.0713, found 278.0707. 1 H NMR (500 MHz, Acetone- d 6 ) δ 7.49 (d, 1H, J = 8.0 Hz), 6.89 (d, 1H, J = 8.5 Hz), 6.78 (d, 1H, J = 8.0 Hz), 6.63 (d, 1H, J = 9.0 Hz) .; 13 C NMR (126 MHz, Acetone- d 6) δ 155.1, 154.1, 146.7, 132.9, 120.4, 118.4, 1163.8 .; 19 F NMR (376 MHz, Acetone- d 6 ) δ −140.4 .; 11 B NMR (128 MHz, Acetone- d 6 ) δ 3.63 .; FT-IR (KBr): 3363, 3036, 2921, 2120, 1596, 1496, 1211, 958, 828 cm -1 .; HRFABMS: m / z calcd for C 12 H 8 BF 3 N 3 O [MK + ] - 278.0713, found 278.0707.
[실시예 22] 포타슘 4- 아지도나프탈렌 -1- 일트리플루오로보레이트의 합성 Example 22 Potassium 4- O map synthesis of borate in-1-yl trifluoroacetate
포타슘 4-아이오도페닐트리플루오로보레이트를 포타슘 4-브로모나프탈렌-1- 일트리플루오로보레이트 313 mg (1.0 mmol)로 대체하여 사용한 것을 제외하고는, 상기 실시예 1과 동일한 방법으로 10 시간 반응 후, 정제하여 표제화합물 226 mg (수율 = 82%)을 얻었다.10 hours in the same manner as in Example 1, except that potassium 4-iodophenyltrifluoroborate was used in place of 313 mg (1.0 mmol) of potassium 4-bromonaphthalen-1-yltrifluoroborate. After the reaction, purification gave 226 mg (yield = 82%) of the title compound.
1H NMR (500 MHz, Acetone-d 6) δ 8.61 (m, 1H), 7.94 (m, 1H), 7.73 (d, 1H, J = 7.0 Hz), 7.34 (m, 2H), 7.16 (d, 1H, J = 7.0 Hz).; 13C NMR (126 MHz, Acetone-d 6) δ 138.2, 132.8, 130.9, 128.7, 126.1, 124.2, 124.1, 121.3, 113.2.; 19F NMR (376 MHz, Acetone-d 6) δ -136.9.; 11B NMR (128 MHz, Acetone- d 6) δ 3.71.; FT-IR (KBr): 3062, 2923, 2116, 1616, 1575, 1421, 1310, 1226, 1157, 1057, 995, 885, 826, 765 cm-1.; HRFABMS: m/z calcd for C10H6BF3N3 [M-K+]- 236.0607, found 236.0619. 1 H NMR (500 MHz, Acetone- d 6 ) δ 8.61 (m, 1H), 7.94 (m, 1H), 7.73 (d, 1H, J = 7.0 Hz), 7.34 (m, 2H), 7.16 (d, 1H, J = 7.0 Hz) .; 13 C NMR (126 MHz, Acetone- d 6) δ 138.2, 132.8, 130.9, 128.7, 126.1, 124.2, 124.1, 121.3, 113.2 .; 19 F NMR (376 MHz, Acetone d 6 ) δ −136.9 .; 11 B NMR (128 MHz, Acetone- d 6 ) δ 3.71.; FT-IR (KBr): 3062, 2923, 2116, 1616, 1575, 1421, 1310, 1226, 1157, 1057, 995, 885, 826, 765 cm -1 .; HRFABMS: m / z calcd for C 10 H 6 BF 3 N 3 [MK + ] - 236.0607, found 236.0619.
[실시예 23] 포타슘 4'- 아지도바이페닐 -4- 일트리플루오로보레이트의 합성 [Example 23] Synthesis of potassium 4'-O map borate with biphenyl-4-yl trifluoroacetate
포타슘 4-아이오도페닐트리플루오로보레이트를 포타슘 4'-아이오도바이페닐-4-일트리플루오로보레이트 386 mg (1.0 mmol)로 대체하여 사용한 것을 제외하고는, 상기 실시예 1과 동일한 방법으로 30 분 반응 후, 정제하여 표제화합물 288 mg (수율 = 96%)을 얻었다.In the same manner as in Example 1, except that potassium 4-iodophenyltrifluoroborate was replaced with 386 mg (1.0 mmol) of potassium 4'-iodobiphenyl-4-yltrifluoroborate. After min reaction, purification afforded 288 mg (yield = 96%) of the title compound.
1H NMR (500 MHz, Acetone-d 6) δ 7.67 (d, 2H, J = 8.5 Hz), 7.57 (d, 2H, J = 8.0 Hz), 7.40 (d, 2H, J = 7.5 Hz), 7.15 (d, 2H, J = 8.5 Hz).; 13C NMR (126 MHz, Acetone-d 6) δ 139.5, 137.9, 136.3, 132.3, 128.0, 124.5, 119.2.; 19F NMR (376 MHz, Acetone-d 6) δ -141.4.; 11B NMR (128 MHz, Acetone- d 6) δ 3.40.; FT-IR (KBr): 3059, 3021, 2127, 2093, 1603, 1493, 1390, 1290, 1225, 970, 814 cm-1.; HRFABMS: m/z calcd for C12H8BF3N3 [M-K+]- 262.0763, found 262.0768. 1 H NMR (500 MHz, Acetone- d 6 ) δ 7.67 (d, 2H, J = 8.5 Hz), 7.57 (d, 2H, J = 8.0 Hz), 7.40 (d, 2H, J = 7.5 Hz), 7.15 (d, 2H, J = 8.5 Hz); 13 C NMR (126 MHz, Acetone- d 6) δ 139.5, 137.9, 136.3, 132.3, 128.0, 124.5, 119.2 .; 19 F NMR (376 MHz, Acetone- d 6) δ -141.4 .; 11 B NMR (128 MHz, Acetone- d 6 ) δ 3.40 .; FT-IR (KBr): 3059, 3021, 2127, 2093, 1603, 1493, 1390, 1290, 1225, 970, 814 cm −1 .; HRFABMS: m / z calcd for C 12 H 8 BF 3 N 3 [MK + ] - 262.0763, found 262.0768.
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