Diisopropylethylamine → 4-amino-2-fluoro-5-methoxy-N-[[1-(pyrrolidin-1-ylmethyl)cyclopropyl]methyl]benzamide

Participants

Role	Name	HCID	Charge
Reactant	Diisopropylethylamine	HCID 81531	—
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-{1-[(Pyrrolidin-1-yl)methyl]cyclopropyl}methanamine	HCID 28064766	—
Reactant	4-Amino-2-fluoro-5-methoxybenzoic acid	HCID 52982963	—
Solvent	Dimethylformamide	HCID 6228	—
Product	4-amino-2-fluoro-5-methoxy-N-[[1-(pyrrolidin-1-ylmethyl)cyclopropyl]methyl]benzamide	HCID 68684751	23%

Reaction Steps

4-amino-2-fluoro-5-methoxy-benzoic acid (Intermediate 183; 500 mg, 2.70 mmol), [1-(pyrrolidin-1-ylmethyl)cyclopropyl]methanamine (Intermediate 33; 417 mg, 2.70 mmol), HATU (1.545 g, 4.05 mmol) and DIPEA (1.415 mL, 8.10 mmol) were dissolved in DMF (8 mL) and left to stir for 3 hours at room temperature. The reaction mixture was loaded onto an SCX-3 column pre-washed with methanol. The column was washed with methanol eluted with 2% 7N ammonia/methanol. Product containing fractions were combined and evaporated and the residue purified on a silica column (5-12% MeOH ammonia/DCM gradient elution) to yield the title compound as an orange-brown solid (200 mg, 23%).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US07709471B2
Source dataset	uspto-grants-2010_05
ORD ID	ord-021a959f7b4d45ae99335f2bccb57ed5
Source note	uspto-grants-2010_05