Potassium Carbonate → Ethyl3-[(2-chloro-5-nitro-pyrimidin-4-yl)-cyclopentyl-amino]-2,2-dimethyl-propanoate

To a stirred clear colourless solution of Ethyl3-(cyclopentylamino)-2,2-dimethyl-propanoate (US 2004/0176380 A1; 29.8 g, 139.7 mmol) in the acetone (700 mL) at room temperature was added potassium carbonate (21.3 g, 153.7 mmol) followed by 2,4-dichloro-5-nitropyrimidine (Aldrich; 29.81 g, 153.7 mmol). The reaction mixture was stirred vigorously at room temperature overnight. Potassium carbonate (7.75 g, 56 mmol) was added stirring continued for a further 4 hours. The reaction mixture was concentrated in vacuo to low volume and partitioned between Ethyl Acetate (600 mL) and water (400 mL). Phases were separated and the aqueous phase re-extracted with Ethyl Acetate (1×200 ml, 1×100 ml). The combined organic extracts were dried using MgSO4 and evaporated to dryness The residue was dissolved in DCM (150 mL) and purified in two batches using a Biotage Flash 75 system with 400 g Si column, conditioned with 10% Ethyl Acetate in isohexane and eluted with 10% Ethyl Acetate in isohexane. Product containing fractions were combined and evaporated giving the title compound as a yellow oil which solidified on standing in a freezer (27.90 g 54%)

1. stirringstirring
2. waitcontinued for a further 4 hours
3. concentrationThe reaction mixture was concentrated in vacuo to low volume
4. custompartitioned between Ethyl Acetate (600 mL) and water (400 mL)
5. customPhases were separated
6. extractionthe aqueous phase re-extracted with Ethyl Acetate (1×200 ml, 1×100 ml)
7. customThe combined organic extracts were dried
8. customevaporated to dryness The residue
9. dissolutionwas dissolved in DCM (150 mL)
10. custompurified in two batches
11. washeluted with 10% Ethyl Acetate in isohexane
12. additionProduct containing fractions
13. customevaporated

ORD record

ord-87d7ba88425148f4bca8990a092bfa68

Source dataset

uspto-grants-2010_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07709471B2