Lithium Hydroxide → 6-(Cyclopentylamino)pyrimidine-4-carboxylic acid

A mixture of methyl 2-chloro-6-[(cyclopentylmethyl)amino]pyrimidine-4-carboxylate (Intermediate 2, 2.00 g; 7.82 mmol; 1.00 eq.), palladium on charcoal (750 mg) and triethylamine (3.27 mL; 23.5 mmol) in EtOH (200 mL) was stirred under an atmosphere of hydrogen for 2 hours. After 2 hours the reaction mixture was filtered on celite and evaporated to give a mixture of methyl 6-(cyclopentylamino)pyrimidine-4-carboxylate and ethyl 6-(cyclopentylamino)pyrimidine-4-carboxylate. The crude mixture was dissolved in a mixture of THF/EtOH/H2O (3/2/1, 120 mL) and treated with an aqueous solution of lithium hydroxide (1N, 23.5 mL, 23.5 mmol). The reaction mixture was stirred at RT for 60 minutes. Water was added (50 mL) and the aqueous layer was washed with DCM (30 mL). The aqueous layer was acidified to pH 5 by addition of an HCl solution (1N). The aqueous layer was evaporated in vacuo to reduce the volume by 30-50%. The resulting white solid was filtered to afford the title compound as a white solid.

1. filtrationAfter 2 hours the reaction mixture was filtered on celite
2. customevaporated
3. customto give
4. stirringThe reaction mixture was stirred at RT for 60 minutes
5. washthe aqueous layer was washed with DCM (30 mL)
6. additionThe aqueous layer was acidified to pH 5 by addition of an HCl solution (1N)
7. customThe aqueous layer was evaporated in vacuo
8. filtrationThe resulting white solid was filtered

ORD record

ord-65c1072c06be418a97f456a5ffefdd10

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08399448B2