Dichloromethane → (S)-1-(3-fluoro-4-(6-isopropyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)-3-(2-fluoroethyl)urea

Participants

Role	Name	HCID	Charge
Reactant	Dichloromethane	HCID 6344	—
Reactant	Sodium Carbonate	HCID 10340	—
Reactant	(S)-4-(2-chloro-6-isopropyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yl)-3-methylmorpholine	HCID 86663166	—
Reactant	N-(2-Fluoroethyl)-N′-[3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]urea	HCID 86663172	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	Ethanol	HCID 702	—
Solvent	Water	HCID 962	—
Solvent	1,2-Dimethoxyethane	HCID 8071	—
Product	(S)-1-(3-fluoro-4-(6-isopropyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)-3-(2-fluoroethyl)urea	HCID 86663179	8.1%

Reaction Steps

A solution of (S)-4-(2-chloro-6-isopropyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yl)-3-methylmorpholine (intermediate 22) (120 mg, 0.404 mmol), 1-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-3-(2-fluoroethyl)urea (intermediate 31) (145 mg, 0.445 mmol), [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium (II), complex with dichloromethane (16 mg, 0.02 mmol) and sodium carbonate (128 mg, 1.21 mmol) in 2 ml of a 7:3:1 mixture of DME:H2O:EtOH respectively was heated in the microwave at 140° C. for 1 hour. The reaction was filtered through celite and purified via preparative HPLC at high pH to yield the title compound (15 mg, 8%).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08785457B2
Source dataset	uspto-grants-2014_07
ORD ID	ord-1ca22ac0c7f746e3b19bf4f545e94484
Source note	uspto-grants-2014_07