Sodium Bicarbonate → Tert-butyl 1-(6-chloro-4-(2-(5-fluoro-2-(2-(2-oxoimidazolidin-1-yl)ethylamino)pyrimidin-4-yl)benzo[b]thiophen-7-yl)pyridin-3-yl)ethylcarbamate

HRID 561030ノート

反応式

HRID 561030 の反応式
[C:1]([O:5][C:6](=[O:18])[NH:7][CH:8]([C:10]1[CH:11]=[N:12][C:13]([Cl:17])=[CH:14][C:15]=1I)[CH3:9])([CH3:4])([CH3:3])[CH3:2].[F:19][C:20]1[C:21]([C:35]2[S:39][C:38]3[C:40](B4OC(C)(C)C(C)(C)O4)=[CH:41][CH:42]=[CH:43][C:37]=3[CH:36]=2)=[N:22][C:23]([NH:26][CH2:27][CH2:28][N:29]2[CH2:33][CH2:32][NH:31][C:30]2=[O:34])=[N:24][CH:25]=1.C([O-])(O)=O.[Na+]>C(#N)C.O.C1(P([C-]2C=CC=C2)C2C=CC=CC=2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].Cl[Pd]Cl>[Cl:17][C:13]1[N:12]=[CH:11][C:10]([CH:8]([NH:7][C:6](=[O:18])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH3:9])=[C:15]([C:40]2[C:38]3[S:39][C:35]([C:21]4[C:20]([F:19])=[CH:25][N:24]=[C:23]([NH:26][CH2:27][CH2:28][N:29]5[CH2:33][CH2:32][NH:31][C:30]5=[O:34])[N:22]=4)=[CH:36][C:37]=3[CH:43]=[CH:42][CH:41]=2)[CH:14]=1

参加物

8

反応物 3

HCID 516892Sodium BicarbonateHCID 666734811-(2-{5-Fluoro-4-[7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzo[b]thiophen-2-yl]-pyrimidin-2-ylamino}-ethyl)-imidazolidin-2-oneHCID 86640498[1-(6-Chloro-4-iodo-pyridin-3-yl)-ethyl]-carbamic acid tert-butyl ester

生成物 1

HCID 86640497Tert-butyl 1-(6-chloro-4-(2-(5-fluoro-2-(2-(2-oxoimidazolidin-1-yl)ethylamino)pyrimidin-4-yl)benzo[b]thiophen-7-yl)pyridin-3-yl)ethylcarbamate収率 55.3%

試薬・触媒・溶媒 4

HCID 24290Palladium Chloride触媒HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)触媒HCID 962Water溶媒HCID 6342Acetonitrile溶媒

反応条件

温度
100 °C

実験手順

In a microwave vial, combine [1-(6-chloro-4-iodo-pyridin-3-yl)-ethyl]-carbamic acid tert-butyl ester (250 mg, 0.65 mmol) and 1-(2-{5-fluoro-4-[7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzo[b]thiophen-2-yl]-pyrimidin-2-ylamino}-ethyl)-imidazolidin-2-one (380 mg, 0.78 mmol), bis(diphenylphosphino)ferrocene)dichloro palladium (53 mg, 0.07 mmol) and NaHCO3 (110 mg, 1.31 mmol) in acetonitrile (7 mL) and water (3 mL). Purge the mixture with nitrogen for 5 min. Heat the mixture at 100° C. for 15 min in a microwave. Remove solvent on a rotovap. Purify by normal phase column chromatography using 0.5% to 5% MeOH in dichloromethane to get off white solid product (220 mg). MS (ES) m/z 612 [M+1]+

後処理

  1. customPurge the mixture with nitrogen for 5 min
  2. customPurify by normal phase column chromatography

出典と根拠

ORDレコード
ord-3b623e63df59401cb1486053ee6778e2
出典データセット
uspto-grants-2011_11
特許番号
US08063212B2

反応ノート

読み込み中…