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 561030노트

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HRID 561030 반응식
[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

참가 물질

8

반응물 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

생성물 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)ethylcarbamate수율 55.3%

시약·촉매·용매 4

HCID 24290Palladium Chloride촉매HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)촉매HCID 962Water용매HCID 6342Acetonitrile용매

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온도
100 °C

실험 절차

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]+

후처리

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

출처 및 근거

ORD 기록
ord-3b623e63df59401cb1486053ee6778e2
출처 데이터셋
uspto-grants-2011_11
특허 번호
US08063212B2

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