Potassium Carbonate → 3-(2-Carbamoyl-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-9-ylethynyl)-3-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester

Participants

Role	Name	HCID	Charge
Reactant	Potassium Carbonate	HCID 11430	—
Reactant	1,3-Bis(diphenylphosphino)propane	HCID 81219	—
Reactant	Tert-butyl 3-ethynyl-3-hydroxypyrrolidine-1-carboxylate	HCID 18366064	—
Reactant	10-Bromo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide	HCID 68312883	—
Catalyst	Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)	HCID 24350	—
Catalyst	palladium(II) acetate	HCID 167845	—
Solvent	Dimethylformamide	HCID 6228	—
Product	3-(2-Carbamoyl-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-9-ylethynyl)-3-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester	HCID 86693100	28.5%

Reaction Steps

This compound was prepared according to a procedure similar to that described in Procedure H. In a solution of 9-Bromo-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carboxylic acid amide (100 mg, 0.32 mmol) in N,N-Dimethyl-formamide (3 mL) were added 1,3-bis(diphenylphosphino)-propane (26 mg, 0.064 mmol), Pd(OAc)2 (7.2 mg, 0.032 mmol), K2CO3 (110 mg, 0.8 mmol), 3-Ethynyl-3-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester (136 mg, 0.64 mmol) and CuI (12 mg, 0.064 mmol). Then the solution was bubbled N2 for 5 min and microwaved for 1 h at 120° C. under nitrogen. The reaction mixture was filtrated and the filtrate was purified by column to afford crude titled compound (40 mg, 28%). LCMS=383.0 [M-56]+.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09034866B2
Source dataset	uspto-grants-2015_05
ORD ID	ord-bf77705285c54988aba1c26ab0cd3862
Source note	uspto-grants-2015_05