Ammonium Hydroxide → 6-Chloro-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide

https://huagongshe.com/reaction/2044036

Participants

Role	Name	HCID	Charge
Reactant	Ammonium Hydroxide	HCID 14923	—
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	6-Chloro-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinic acid	HCID 57489600	—
Solvent	Dimethylformamide	HCID 6228	—
Solvent	Lithium Chloride	HCID 433294	—
Product	6-Chloro-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide	HCID 57489601	94.2%

Reaction Steps

To a solution of 6-chloro-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinic acid (6.60 g, 18.24 mmol), NH4OH (40.1 mL, 20.07 mmol), and N-ethyl-N-isopropylpropan-2-amine (3.54 g, 27.4 mmol) in DMF (40 mL) was added HATU (13.87 g, 36.5 mmol) at rt. The solution became cloudy but eventually cleared up as the HATU was added. The reaction was completed after 1 h. The reaction mixture was diluted with 10% LiCl and extracted with ethyl acetate three times. The organic extracts was washed with 10% LiCl, water twice, and then concentrated. The light yellow solid was triturated with CH2Cl2 to give 3.8 g. A second trituration gave 1.95 g, and a third trituration gave 462 mg. A total of 6.2 g of 6-chloro-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide was obtained.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08586751B2
Source dataset	uspto-grants-2013_11
ORD ID	ord-2e71f5b679ed4947b75ee1a4095eb101
Source note	uspto-grants-2013_11