Cesium carbonate → ethyl 2-(2-((4-(tert-butoxycarbonyl)piperazin-1-yl)methyl)-4-cyclopentyl-5-(methoxycarbonyloxy)phenylcarbamoyl)-6-cyano-2H-benzo[b][1,4]oxazine-4(3H)-carboxylate

Participants

Role	Name	HCID	Charge
Reactant	Cesium carbonate	HCID 10796	—
Reactant	2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl	HCID 11155794	—
Reactant	HCID 59394958	HCID 59394958	—
Reactant	HCID 178452281	HCID 178452281	—
Catalyst	palladium(II) acetate	HCID 167845	—
Solvent	Oxolane--water (1/1)	HCID 21881883	—
Product	ethyl 2-(2-((4-(tert-butoxycarbonyl)piperazin-1-yl)methyl)-4-cyclopentyl-5-(methoxycarbonyloxy)phenylcarbamoyl)-6-cyano-2H-benzo[b][1,4]oxazine-4(3H)-carboxylate	HCID 59394951	24.1%

Reaction Conditions

Temperature	100 °C

Reaction Steps

A mixture of ethyl 2-(2-bromo-4-cyclopentyl-5-(methoxycarbonyloxy)phenylcarbamoyl)-6-cyano-2H-benzo[b][1,4]oxazine-4(3H)-carboxylate (53.0 mg, 0.092 mmol), Pd(OAc)2 (0.6 mg, 0.003 mmol), X-Phos (2.6 mg, 0.006 mmol), tert-butyl 4-(trifluoromethylboranylmethyl)piperazine-1-carboxylate (25.0 mg, 0.09 mmol) and Cs2CO3 (90 mg, 0.28 mmol) in THF/water (10:1, 400 μL) under N2 atmosphere was heated under microwave irradiation at 100° C. for 1 h. The reaction was filtered and purified by HPLC (10-99% CH3CN/water) to provide ethyl 2-(2-((4-(tert-butoxycarbonyl)piperazin-1-yl)methyl)-4-cyclopentyl-5-(methoxycarbonyloxy)phenylcarbamoyl)-6-cyano-2H-benzo[b][1,4]oxazine-4(3H)-carboxylate (15.0 mg, 24% yield). LC/MS m/z 692.5 [M+H]+.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08367660B2
Source dataset	uspto-grants-2013_02
ORD ID	ord-7454c0552029480db82131feb6a257c0
Source note	uspto-grants-2013_02