Diisopropylethylamine → 3-(Chloromethyl)pyridine

Participants

Role	Name	HCID	Charge
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	3-Pyridinecarbonyl chloride, hydrochloride (1:1)	HCID 88438	—
Reactant	(R)-3-[4-(4-ethoxy-phenylamino)-piperidin-1-yl]-butyronitrile	HCID 68971325	—
Solvent	Tetrahydrofuran	HCID 8028	—
Product	3-(Chloromethyl)pyridine	HCID 18358	88%
Product	n-[(r)-1-(2-Cyano-1-methyl-ethyl)-piperidin-4-yl]-n-(4-ethoxy-phenyl)-nicotinamide	HCID 68971112	—

Reaction Conditions

Temperature	80 °C

Reaction Steps

A solution of the above nitrile (0.18 g, 0.63 mmol) and nicotinoyl chloride hydrochloride (0.45 g, 2.5 mmol) in THF (6 mL) was then treated with DIPEA (0.55 mL, 3.2 mmol) and stirred at 80° C. for 16 h. The reaction was cooled to room temperature, concentrated under reduced pressure, diluted with CH2Cl2 (10 mL) and washed with brine solution (2×10 mL). The combined organic extracts were then dried (Na2SO4), filtered and concentrated and the crude material purified by flash column chromatography on silica gel (25:1:0.1 CH2Cl2/MeOH/NH4OH) to afford N-[(R)-1-(2-cyano-1-methyl-ethyl)-piperidin-4-yl]-N-(4-ethoxy-phenyl)-nicotinamide impure with nicotinyl chloride (88%).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US07498346B2
Source dataset	uspto-grants-2009_03
ORD ID	ord-b222b2d037df440cacc60dbb104c5f4c
Source note	uspto-grants-2009_03