Sodium Carbonate → N2-{4-[4-amino-1-(2-hydroxyethyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-1-methyl-1H-2-indolecarboxamide

HRID 897832노트

반응식

HRID 897832 반응식
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:12][CH2:13][OH:14])[N:9]=[C:10](I)[C:3]=12.[CH3:15][O:16][C:17]1[CH:22]=[C:21](B2OC(C)(C)C(C)(C)O2)[CH:20]=[CH:19][C:18]=1[NH:32][C:33]([C:35]1[N:36]([CH3:44])[C:37]2[C:42]([CH:43]=1)=[CH:41][CH:40]=[CH:39][CH:38]=2)=[O:34].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]>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:12][CH2:13][OH:14])[N:9]=[C:10]([C:21]3[CH:20]=[CH:19][C:18]([NH:32][C:33]([C:35]4[N:36]([CH3:44])[C:37]5[C:42]([CH:43]=4)=[CH:41][CH:40]=[CH:39][CH:38]=5)=[O:34])=[C:17]([O:16][CH3:15])[CH:22]=3)[C:3]=12

참가 물질

7

반응물 3

HCID 10340Sodium CarbonateHCID 22346783HCID 22346783, 화합물2회HCID 22347095N-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-methyl-1H-indole-2-carboxamide

생성물 1

HCID 22346971N2-{4-[4-amino-1-(2-hydroxyethyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-1-methyl-1H-2-indolecarboxamide수율 84%

시약·촉매·용매 3

HCID 11979704Tetrakis(triphenylphosphine)palladium촉매HCID 962Water용매HCID 80711,2-Dimethoxyethane용매

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온도
85 °C

실험 절차

A mixture of 2-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-ethanol (Intermediate 3) (0.364 g, 1.19 mol), N2-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-methyl-1H-2-indolecarboxamide (0.485 g, 1.19 mmol), palladium tetrakis(triphenylphosphine) (0.138 g, 0.119 mmol), and sodium carbonate (0.303 g, 2.86 mmol) in DME (12 mL) and water (12 mL) was heated at 85° C. for 4 h then cooled to ambient temperature. The DME was removed in vacuo and the resulting precipitate was collected by filtration and rinsed with water (50 mL) and ether (50 mL) to afford N2-{4-[4-amino-1-(2-hydroxyethyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-1-methyl-1H-2-indolecarboxamide as a tan solid (0.459 g, 1.00 mmol): 1H NMR (d6-DMSO, 400 MHz): δH 9.44 (1H, s), 8.26 (1H, s), 8.12 (1H, d, J=8.0 Hz), 7.70 (1H, d, J=8.0 Hz), 7.59 (1H, d, J=8.4 Hz), 7.29-7.41 (6H, m), 7.15 (1H, t, J=7.4 Hz), 4.90 (1H, t, J=5.8 Hz), 4.41 (2H, t, J=5.8 Hz), 4.04 (3H, s), 3.96 (3H, s), and 3.86 (2H, q, J=5.9 Hz); 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 10.52 min.

후처리

  1. temperaturethen cooled to ambient temperature
  2. customThe DME was removed in vacuo
  3. filtrationthe resulting precipitate was collected by filtration
  4. washrinsed with water (50 mL) and ether (50 mL)

출처 및 근거

ORD 기록
ord-856df9964a1a4cb5b44aa23b7ffe7e70
출처 데이터셋
uspto-grants-2005_07
특허 번호
US06921763B2

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