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 561030Notes

Reaction equation

[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

Participants

Conditions

Temperature: 100 °C

Procedure

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]+

Workup

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

Sources & evidence

ORD record: ord-3b623e63df59401cb1486053ee6778e2
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08063212B2

Reaction notes

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