Diisopropylethylamine → 2,2-difluoro-N-(2-(6-((4-(2-hydroxypropan-2-yl)piperidin-1-yl)methyl)-4-morpholinopyrido[3,2-d]pyrimidin-2-ylamino)phenyl)propanamide

Participants

Role	Name	HCID	Charge
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	2,2-Difluoropropionic acid	HCID 2782825	—
Reactant	Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)	HCID 9886157	—
Reactant	2-(1-((2-(2-Aminophenylamino)-4-morpholinopyrido[3,2-d]pyrimidin-6-yl)methyl)piperidin-4-yl)propan-2-ol	HCID 58404971	—
Solvent	Dimethylformamide	HCID 6228	—
Product	2,2-difluoro-N-(2-(6-((4-(2-hydroxypropan-2-yl)piperidin-1-yl)methyl)-4-morpholinopyrido[3,2-d]pyrimidin-2-ylamino)phenyl)propanamide	HCID 58405024	—

Reaction Steps

2-(1-((2-(2-aminophenylamino)-4-morpholinopyrido[3,2-d]pyrimidin-6-yl)methyl)piperidin-4-yl)propan-2-ol was reacted with 2,2-difluoropropanoic acid (2 eq), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, 1.5 eq) and DIPEA (4 eq) in DMF (4 mL) for 1 hr (hour). The reaction mixture was extracted with EtOAc and bicarbonate solution and the organic layer was dried with Magnesium sulfate, filtered, evaporated and purified via flash column chromatography to get 50 mg of 2,2-difluoro-N-(2-(6-((4-(2-hydroxypropan-2-yl)piperidin-1-yl)methyl)-4-morpholinopyrido[3,2-d]pyrimidin-2-ylamino)phenyl)propanamide. This intermediate was reacted with acetic acid (1.6 mL) over one week to yield 4.1 mg of 120 following reverse phase HPLC purification. MS (Q1) 552.3 (M)+

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08563540B2
Source dataset	uspto-grants-2013_10
ORD ID	ord-a59bd9ce41aa4208b6d559395dff04ba
Source note	uspto-grants-2013_10