Sodium Carbonate → N2-(2-chloro-5-((R)-2-hydroxypropylcarbamoyl)phenyl)-N2-methyl-N8-(2-(methylsulfonyl)ethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide

Participants

Reaction Conditions

Reaction Steps

A suspension of 8-bromo-N-(2-chloro-5-((R)-2-hydroxypropylcarbamoyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide (500 mg, 0.91 mmol), Pd(OAc)2 (10 mg, 0.045 mmol), Xantphos (53 mg, 0.091 mmol), MeSO2(CH2)2NH2.HCl (218 mg, 1.36 mmol) and Na2CO3 (289 mg, 2.73 mmol) in toluene (5 mL) and DMF (5 mL) was heated at 80° C. under atmosphere of CO from balloon overnight. Then it was filtrated and concentrated, the crude product was purified by pre-TLC (DCM:MeOH=10:1 as eluted solvent) to give 387 (101.5 mg, yield 18%). 1H NMR (DMSO-d6, 400 MHz): δ8.73 (s, 1H, NH), 8.60 (s, 1H, NH), 8.12-7.45 (m, 6H, ArH), 6.61 (s, 1H, ═CH), 4.76 (d, J=4.8 Hz, 1H, OH), 4.20 (br s, 2H, CH2), 3.80-3.77 (m, 1H, CH), 3.67-2.98 (m, 14H, CH3, CH2), 1.06 (t, J=5.2 Hz, 3H, CH3). LC-MS: (ESI, m/z)=542 [M+Na]+

Provenance & Evidence