1-(2-Fluoroethyl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea → (S)-ethyl 2-(4-(3-(2-fluoroethyl)ureido)phenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate

Participants

Role	Name	HCID	Charge
Reactant	1-(2-Fluoroethyl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea	HCID 44607353	—
Reactant	(S)-tert-butyl 2-(4-(3-ethylureido)phenyl)-4-(3-methylmorpholino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate	HCID 59239149	—
Reactant	HCID 86663155	HCID 86663155	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Product	(S)-ethyl 2-(4-(3-(2-fluoroethyl)ureido)phenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate	HCID 86663162	13%

Reaction Steps

Method as described for intermediate 5 using (S)-ethyl 2-chloro-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate (intermediate 11) and 1-(2-fluoroethyl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea as starting materials and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) as catalyst. The mixture was filtered through a celite 545 pre-packed cartridge (2.5 g), washed with MeOH and solvent removed in vacuo. The residue was purified first by flash chromatography using a gradient of 0-20% MeOH/DCM as eluent, then prep HPLC (low pH) yielding the title compound (9.2 mg, 0.02 mmol, 13%).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08785457B2
Source dataset	uspto-grants-2014_07
ORD ID	ord-68d687f3ee254d01a650cebea0dee3c5
Source note	uspto-grants-2014_07