Sodium Carbonate → N2-(2-chloro-5-((S)-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-((S)-2-hydroxypropylcarbamoyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide (400 mg, 0.73 mmol), Pd(OAc)2 (8 mg, 0.037 mmol), Xantphos (42 mg, 0.073 mmol), MeSO2(CH2)2NH2.HCl (175 mg, 1.095 mmol) and Na2CO3 (232 mg, 2.19 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 (eluted by DCM: MeOH=10:1) to give 438 (191.9 mg, yield 42%). 1H NMR (DMSO-d6, 400 MHz): δ68.74 (t, J=5.2 Hz, 1H, NH), 8.62 (t, J=5.2 Hz, 1H, NH), 8.12-7.44 (m, 6H, ArH), 6.61 (s, 1H, ═CH), 4.77 (d, J=4.8 Hz, 1H, OH), 4.20 (br s, 2H, CH2), 3.80-3.75 (m, 1H, CH), 3.67-2.98 (m, 14H, CH3, CH2), 1.05 (t, J=6.0 Hz, 3H, CH3). LC-MS: (ESI, m/z)=620 [M+H]+

Provenance & Evidence