Methanamine, N-methoxy-, hydrochloride (1:1) → Tert-butyl 4-(5-(methoxy(methyl)carbamoyl)pyridin-2-yl)piperazine-1-carboxylate

Participants

Role	Name	HCID	Charge
Reactant	Methanamine, N-methoxy-, hydrochloride (1:1)	HCID 81138	—
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	6-(4-((Tert-butoxy)carbonyl)piperazin-1-yl)pyridine-3-carboxylic acid	HCID 2771823	—
Reactant	Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)	HCID 9886157	—
Solvent	Dimethylformamide	HCID 6228	—
Product	Tert-butyl 4-(5-(methoxy(methyl)carbamoyl)pyridin-2-yl)piperazine-1-carboxylate	HCID 86631940	63.7%

Reaction Steps

6-(4-(tert-Butoxycarbonyl)piperazin-1-yl)nicotinic acid (2.0 g, 6.5 mmol) was taken into DMF (10 mL) followed by addition of HATU (2.48 g, 6.5 mmol), N,N-diisopropylethylamine (2.5 mL, 14.1 mmol) and N,O-dimethylhydroxylamine hydrochloride (652 mg, 6.7 mmol), and the mixture was stirred at room temperature over 12 hours. The resulting solution was partitioned with ethyl acetate and water then the organic phase washed with water (3×), 10% aqueous citric acid (2×) then 0.5M aqueous sodium hydroxide and brine. The organic solution was dried over anhydrous sodium sulfate, filtered and concentrated, then purified by silica gel flash chromatography with ethyl ether as eluent to provide tert-butyl 4-(5-(methoxy(methyl)carbamoyl)pyridin-2-yl)piperazine-1-carboxylate (1.45 g). MS (EI) for C17H26N4O4: 351 (MH+).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08012956B2
Source dataset	uspto-grants-2011_09
ORD ID	ord-6804a1280c1a484da5c92b6af64ccca4
Source note	uspto-grants-2011_09