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

Role	Name	HCID	Charge
Reactant	Sodium Carbonate	HCID 10340	—
Reactant	1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)	HCID 636044	—
Reactant	Ethanamine, 2-(methylsulfonyl)-, hydrochloride (1:1)	HCID 17749886	—
Reactant	HCID 67050592	HCID 67050592	—
Catalyst	palladium(II) acetate	HCID 167845	—
Solvent	Toluene	HCID 1140	—
Solvent	Dimethylformamide	HCID 6228	—
Product	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	HCID 67050604	179.9%

Reaction Conditions

Temperature	80 °C

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

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08263633B2
Source dataset	uspto-grants-2012_09
ORD ID	ord-356d01c593c8494e8ed90301e95d3594
Source note	uspto-grants-2012_09