一水碳酸钠 → N1-phenyl-2-(4-{4-chloro-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidine-5-yl}phenyl)acetamide

HRID 51623

反应方程式

HRID 51623 反应方程式
[Cl:1][C:2]1[C:3]2[C:10](I)=[CH:9][N:8]([C@H:12]3[CH2:17][CH2:16][C@@H:15]([N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)[CH2:14][CH2:13]3)[C:4]=2[N:5]=[CH:6][N:7]=1.[C:25]1([NH:31][C:32](=[O:49])[CH2:33][C:34]2[CH:39]=[CH:38][C:37](B3OC(C)(C)C(C)(C)O3)=[CH:36][CH:35]=2)[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.O.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O>[C:25]1([NH:31][C:32](=[O:49])[CH2:33][C:34]2[CH:39]=[CH:38][C:37]([C:10]3[C:3]4[C:2]([Cl:1])=[N:7][CH:6]=[N:5][C:4]=4[N:8]([CH:12]4[CH2:17][CH2:16][CH:15]([N:18]5[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]5)[CH2:14][CH2:13]4)[CH:9]=3)=[CH:36][CH:35]=2)[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1

参与物

6

反应物 3

HCID 2735133一水碳酸钠HCID 22736360N1-phenyl-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]acetamideHCID 178480945HCID 178480945，化合物

产物 1

HCID 22736191N1-phenyl-2-(4-{4-chloro-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidine-5-yl}phenyl)acetamide收率 62.5%

试剂、催化剂与溶剂 2

HCID 962聚[6-[4-(4-氰基苯基)苯氧基]己基甲基丙烯酸酯]溶剂HCID 8071乙二醇二甲醚溶剂

反应条件

温度
85 °C

实验过程

A mixture of cis-4-chloro-5-iodo-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidine (1.0 g, 2.18 mmol), N1-phenyl -2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]acetamide (0.81 g, 2.40 mmol), tetrakis(triphenyl-phosphine)palladium (70 mg, 0.131 mmol) and sodium carbonate monohydrate (0.65 g, 2.40 mmol) in ethylene glycol dimethyl ether (16 mL) and water (8 mL) was heated at 85° C. under an atmosphere of nitrogen for 18 hours. The mixture was cooled to ambient temperature and the solvent was removed under reduced pressure. The residue was purified by flash chromatography on silica using dichloromethane/methanol (9:1) as an eluent to give N1-phenyl-2-(4-{4-chloro-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidine-5-yl}phenyl)acetamide (0.74 g, 62%): 1H NMR (DMSO-d6, 400 MHz) 10.20(s, 1H), 8.66(s, 1H), 7.81(s, 1H), 7.62(d, 2H), 7.52(d, 2H), 7.41(d, 2H), 7.31(t, 2H), 7.04(t, 1H), 4.83(m, 1H), 3.70(s, 2H)<2.05-2.5(m, 13H), 2.17(s, 3H), 1.59-1.77(m, 4H); RP-HPLC (Hypersil HS C18, 5 m, 100 A, 250×4.6 mm; 25%-100% acetontrile over 10 min, 1 mL/min) tr 8.23 min.; MS:MH+ 543.2.

后处理

  1. temperatureThe mixture was cooled to ambient temperature
  2. customthe solvent was removed under reduced pressure
  3. customThe residue was purified by flash chromatography on silica

来源与证据

ORD记录
ord-040fd0ec05eb45a0ae629de36d5f1a20
来源数据集
uspto-grants-2004_03
专利号
US06713474B2

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