Sodium Carbonate → N2-(2-chloro-5-((2-hydroxyethyl)(methyl)carbamoyl)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 58204024	HCID 58204024	—
Catalyst	palladium(II) acetate	HCID 167845	—
Solvent	Toluene	HCID 1140	—
Product	N2-(2-chloro-5-((2-hydroxyethyl)(methyl)carbamoyl)phenyl)-N2-methyl-N8-(2-(methylsulfonyl)ethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide	HCID 58203963	120.7%

Reaction Conditions

Temperature	80 °C

Reaction Steps

A suspension of 8-bromo-N-(2-chloro-5-((2-hydroxyethyl)(methyl)carbamoyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide (400 mg, 0.76 mmol), Pd(OAc)2 (10 mg, 0.045 mmol), Xantphos (44 mg, 0.076 mmol), MeSO2CH2CH2NH2.HCl (181 mg, 1.14 mmol) and Na2CO3 (242 mg, 2.28 mmol) in toluene (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 column (EtOAc: MeOH=10:1) to afford 386 (56.9 mg, yield: 12%). 1HNMR (DMSO-d6, 400 MHz): δ8.71 (t, J=5.6 Hz, 1H), 7.71-7.41 (m, 6H), 6.70 (s, 1H), 4.83-4.73 (m, 1H), 4.18-4.15 (m, 2H), 3.64-2.88 (m, 19H). LC-MS: (ESI, m/z)=620 [M+H]+

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08263633B2
Source dataset	uspto-grants-2012_09
ORD ID	ord-e29fc5080106479ba8d9a43a40d1bb71
Source note	uspto-grants-2012_09