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 897817ノート

反応式

HRID 897817 の反応式
[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

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 4

HCID 11979704Tetrakis(triphenylphosphine)palladium触媒HCID 22347319N1-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2-fluoro-4-(trifluoromethyl)benzamide触媒HCID 962Water溶媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
85 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-79afe78aa20b4de0a31624911bd45a86
出典データセット
uspto-grants-2005_07
特許番号
US06921763B2

反応ノート

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