Triethylamine → 3-(9-((5-chloro-2-((2,3-dimethyl-2H-indazol-6-yl)amino)pyrimidin-4-yl)amino)-3-azaspiro[5.5]undecan-3-yl)-3-oxopropanenitrile

Participants

Role	Name	HCID	Charge
Reactant	Triethylamine	HCID 8471	—
Reactant	Cyanoacetic acid	HCID 9740	—
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	N4-(9-azaspiro[5.5]undecan-3-yl)-5-chloro-N2-(2,3-dimethylindazol-6-yl)pyrimidine-2,4-diamine	HCID 118390164	—
Solvent	Dimethylformamide	HCID 6228	—
Solvent	Dichloromethane	HCID 6344	—
Product	3-(9-((5-chloro-2-((2,3-dimethyl-2H-indazol-6-yl)amino)pyrimidin-4-yl)amino)-3-azaspiro[5.5]undecan-3-yl)-3-oxopropanenitrile	HCID 118390181	30.7%

Reaction Steps

To a solution of 5-chloro-N2-(2,3-dimethyl-2H-indazol-6-yl)-N4-(3-azaspiro[5.5]undecan-9-yl)pyrimidine-2,4-diamine (485.3 mg, 1.10 mmol) and 2-cyanoacetic acid (137.0 mg, 1.61 mmol) in a mixture of DCM (40 mL) and DMF (10 mL) were added HATU (520.8 mg, 1.37 mmol) and Et3N (0.36 g, 3.55 mmol). After addition, the reaction mixture was stirred at rt for 6 h, then quenched with H2O (30 mL) and extracted with DCM (100 mL×3). The combined organic phases were washed with brine (100 mL), dried over anhydrous Na2SO4, concentrated in vacuo. The residue was purified by silica gel column chromatography (MeOH/DCM (v/v)=1/50) to give the title compound as a beige solid (171.0 mg, 30.6%).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09399637B2
Source dataset	uspto-grants-2016_07
ORD ID	ord-c944362e85954db6b7549138b1dad0f5
Source note	uspto-grants-2016_07