Sodium Carbonate → N1-{4-[4-amino-1-(4-formylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-2-fluoro-4-(trifluoromethyl)benzamide

HRID 897817노트

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HRID 897817 반응식
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C:12]3[CH:19]=[CH:18][C:15]([CH:16]=[O:17])=[CH:14][CH:13]=3)[N:9]=[C:10](I)[C:3]=12.[CH3:20][O:21][C:22]1[CH:27]=[C:26](B2OC(C)(C)C(C)(C)O2)[CH:25]=[CH:24][C:23]=1[NH:37][C:38](=[O:50])[C:39]1[CH:44]=[CH:43][C:42]([C:45]([F:48])([F:47])[F:46])=[CH:41][C:40]=1[F:49].C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd].COC1C=C(B2OC(C)(C)C(C)(C)O2)C=CC=1NC(=O)C1C=CC(C(F)(F)F)=CC=1F>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C:12]3[CH:19]=[CH:18][C:15]([CH:16]=[O:17])=[CH:14][CH:13]=3)[N:9]=[C:10]([C:26]3[CH:25]=[CH:24][C:23]([NH:37][C:38](=[O:50])[C:39]4[CH:44]=[CH:43][C:42]([C:45]([F:47])([F:48])[F:46])=[CH:41][C:40]=4[F:49])=[C:22]([O:21][CH3:20])[CH:27]=3)[C:3]=12

참가 물질

8

반응물 3

HCID 10340Sodium CarbonateHCID 223468554-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)benzaldehydeHCID 22347319N1-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2-fluoro-4-(trifluoromethyl)benzamide

생성물 1

HCID 11444225N1-{4-[4-amino-1-(4-formylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-2-fluoro-4-(trifluoromethyl)benzamide수율 67%

시약·촉매·용매 4

HCID 11979704Tetrakis(triphenylphosphine)palladium촉매HCID 22347319N1-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2-fluoro-4-(trifluoromethyl)benzamide촉매HCID 962Water용매HCID 80711,2-Dimethoxyethane용매

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온도
85 °C

실험 절차

A mixture of 4-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)benzaldehyde (0.400 g, 1.09 mmol), N1-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2-fluoro-4-(trifluoromethyl)benzamide (0.735 g, 1.20 mmol), palladium tetrakis(triphenylphosphine) (0.127 g, 0.110 mmol), and sodium carbonate (0.279 g, 2.63 mmol) in DME (10 mL) and water (10 mL) was heated at 85° C. for 1 h. Additional N1-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2-fluoro-4-(trifluoromethyl)benzamide (0.026 g, 0.059 mmol) was added and the reaction mixture was heated at 85° C. for 4 h. The reaction mixture was cooled to ambient temperature and filtered. The residual solid was washed with methanol (50 mL) and DMF (50 mL), and the combined filtrates were concentrated to afford N1-{4-[4-amino-1-(4-formylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-2-fluoro-4-(trifluoromethyl)benzamide as a beige solid (0.402 g, 0.730 mmol): 1H NMR (d6-DMSO, 400 MHz): δH 10.05 (1H, s), 9.96 (1H, d, J=4.0 Hz), 8.62 (1H, d, J=8.4 Hz), 8.46 (1H, s), 8.39 (1H, d, J=6.8 Hz), 8.12 (2H, d, J=8.8 Hz), 8.02-8.03 (1H, m), 7.84-8.00 (1H, m), 7.75-7.77 (1H, m), 7.51 (1H, s), 7.43 (1H, d, J=8.0 Hz), 3.97 (3H, s); RP-HPLC (Hypersil C18, 5 μm, 100 Å, 15 cm; 5%-100% acetonitrile-0.1 M ammonium acetate over 15 min, 1 mL/min). Rt 12.46 min. MS: MH+ 551.2.

후처리

  1. temperaturethe reaction mixture was heated at 85° C. for 4 h
  2. temperatureThe reaction mixture was cooled to ambient temperature
  3. filtrationfiltered
  4. washThe residual solid was washed with methanol (50 mL) and DMF (50 mL)
  5. concentrationthe combined filtrates were concentrated

출처 및 근거

ORD 기록
ord-79afe78aa20b4de0a31624911bd45a86
출처 데이터셋
uspto-grants-2005_07
특허 번호
US06921763B2

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