Dichloromethane → (S)-1-(4-(4-(3-methylmorpholino)pyrimidin-2-yl)phenyl)-3-(pyridin-4-yl)urea

Participants

Role	Name	HCID	Charge
Reactant	Dichloromethane	HCID 6344	—
Reactant	Sodium Carbonate	HCID 10340	—
Reactant	1-(Pyridin-4-yl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea	HCID 66687800	—
Reactant	(S)-4-(2-Chloropyrimidin-4-yl)-3-methylmorpholine	HCID 72942067	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	Water 1,2-dimethoxyethane	HCID 18180031	—
Product	(S)-1-(4-(4-(3-methylmorpholino)pyrimidin-2-yl)phenyl)-3-(pyridin-4-yl)urea	HCID 53379670	—

Reaction Steps

(S)-4-(2-chloropyrimidin-4-yl)-3-methylmorpholine (intermediate 3) (100 mg, 0.47 mmol) was stirred with 1-(pyridin-4-yl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (intermediate 30) (175 mg, 0.52 mmol), Na2CO3 (149 mg, 1.4 mmol) and Pd(dppf)Cl2:DCM (19 mg, 0.02 mmol) in DME:Water (4:1)(5 ml) for 30 mins at 130° C. in a microwave. The reaction mixture was filtered through a celite545 cake and washed with methanol. The solvent was removed in vacuo and the crude residue was purified by prep HPLC at high pH. Further purification was achieved using an SCX-2 cartridge yielding the title compound. (32 mg, 17%)

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09249129B2
Source dataset	uspto-grants-2016_02
ORD ID	ord-3663025fa057463b86756095fa7e3500
Source note	uspto-grants-2016_02