4-Methylmorpholine → 2-(6-Bromo-isoquinolin-1-yl carbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Participants

Role	Name	HCID	Charge
Reactant	4-Methylmorpholine	HCID 7972	—
Reactant	1,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-	HCID 85083	—
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	1-Amino-6-bromoisoquinoline	HCID 22607616	—
Solvent	Dimethylformamide	HCID 6228	—
Product	2-(6-Bromo-isoquinolin-1-yl carbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester	HCID 66620523	115.4%

Reaction Steps

To a mixture of 6-Bromo-isoquinolin-1-ylamine (0.80 g), Boc-L-proline (0.803 g), and 4-methylmorpholine (0.83 mL) in DMF (10 mL) was added HATU (1.39 g). Reaction mixture was stirred for 6 hours. Additional Boc-L-proline (0.803 g), 4-methylmorpholine (0.83 mL) and HATU (1.39 g) were added and reaction stirred overnight at ambient temperature and then concentrated. The residue was dissolved in ethyl acetate and washed with 10:1 H2O/saturated sodium bicarbonate solution, 5% lithium chloride solution, brine and dried (MgSO4), concentrated and purified by flash column chromatography (silica gel, 20 to 70% ethyl acetate/hexanes) to give 2-(6-Bromo-isoquinolin-1-yl carbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (1.74 g): LCMS-ESI+: calc'd for C19H23BrN3O3: 421.31 (M+H+). Found: 419.8, 421.8 (M+H+).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08822430B2
Source dataset	uspto-grants-2014_09
ORD ID	ord-131b828668184cd4aa33d7fb88522739
Source note	uspto-grants-2014_09