Carbonic acid sodium salt (1:2) → N-[2-(3,3-Dimethyl-but-1-enyl)-benzyloxy]-2-[(pyridin-4-ylmethyl)-amino]-benzamide

HRID 1663129笔记

反应方程式

HRID 1663129 反应方程式
I[C:2]1[CH:26]=[CH:25][CH:24]=[CH:23][C:3]=1[CH2:4][O:5][NH:6][C:7](=[O:22])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[NH:14][CH2:15][C:16]1[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=1.[CH3:27][C:28]([CH3:35])([CH3:34])[CH:29]=[CH:30]B(O)O.C(=O)([O-])[O-].[Na+].[Na+].C([O-])(=O)C.[NH4+]>C1(C)C=CC=CC=1.[Pd].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>[CH3:27][C:28]([CH3:35])([CH3:34])[CH:29]=[CH:30][C:2]1[CH:26]=[CH:25][CH:24]=[CH:23][C:3]=1[CH2:4][O:5][NH:6][C:7](=[O:22])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[NH:14][CH2:15][C:16]1[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=1

参与物

7

反应物 4

HCID 10340Carbonic acid sodium salt (1:2)2 次HCID 517165乙酸铵HCID 27632983,3-Dimethyl-1-butenylboronic acid2 次HCID 11487973N-((2-iodobenzyl)oxy)-2-((pyridin-4-ylmethyl)amino)benzamide

产物 1

HCID 73096176N-[2-(3,3-Dimethyl-but-1-enyl)-benzyloxy]-2-[(pyridin-4-ylmethyl)-amino]-benzamide收率 94.8%

试剂、催化剂与溶剂 2

HCID 11979704四三苯基膦钯催化剂2 次HCID 1140甲苯溶剂

反应条件

温度
120 °C

实验过程

Argon was bobbled through a mixture of N-(2-Iodo-benzyloxy)-2-[(pyridin-4-ylmethyl)-amino]-benzamide (example 360, 151 mg, 0.33 mmol) in toluene (20 ml) for 10 to 15 minutes. Tetrakis(triphenylphosphine) palladium (19 mg) was added and the mixture was stirred for 10 minutes before addition of 3,3-dimethyl-1-butenylboronic acid (Aldrich, 50 mg) and a degassed 2M solution of sodium carbonate (0.329 ml). The reaction flask (screw-cap) was sealed and the reaction mixture was heated to 120° C. for 3 hours. More tetrakis(triphenylphosphine) palladium (0.05 eq.), 2M sodium carbonate (0.329 ml), and 3,3-dimethyl-1-butenylboronic acid (50 mg) was added and stirring was continued at 120° C. over night. The mixture was cooled to room temperature and 25% ammonium acetate was added and stirring was continued for 10 min. The mixture was partitioned between EtOAc and water. The aqueous phase was extracted with EtOAc and the combined organic layers were washed with brine, dried (MgSO4) and evaporated under reduced pressure. The residue was subjected to chromatography on silica gel (elution with 1% methanol in dichloromethane v/v) and gave the title compound (130 mg). 13C-NMR (CDCl3) δ 168.9, 149.8, 149.1, 148.7, 145.1, 138.8, 133.4, 131.1, 129.2, 127.4, 126.8, 126.2, 122.0, 121.5, 115.7, 112.8, 112.0, 76.2, 46.1, 33.8, 29.6.

后处理

  1. customThe reaction flask (screw-cap)
  2. customwas sealed
  3. waitwas continued at 120° C. over night
  4. temperatureThe mixture was cooled to room temperature
  5. stirringstirring
  6. customThe mixture was partitioned between EtOAc and water
  7. extractionThe aqueous phase was extracted with EtOAc
  8. washthe combined organic layers were washed with brine
  9. dry with materialdried (MgSO4)
  10. customevaporated under reduced pressure
  11. washelution with 1% methanol in dichloromethane v/v) and

来源与证据

ORD记录
ord-77987d5f2ecf49febc0670d69343d582
来源数据集
uspto-grants-2011_10
专利号
US08034811B2

反应笔记

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