Diisopropylethylamine → 5-methyl-N-(2-(methylamino)ethyl)-4-(2-(tetrahydro-2H-pyran-4-yloxy)pyridin-3-ylamino)thieno[2,3-d]pyrimidine-6-carboxamide

Temperature

0 °C

HATU (0.157 g, 0.41 mmol) was added into a mixture of 5-methyl-4-(2-(tetrahydro-2H-pyran-4-yloxy)pyridin-3-ylamino)thieno[2,3-d]pyrimidine-6-carboxylic acid (0.145 g, 0.38 mmol) and Hünig's base (65 μL, 0.38 mmol) in DMF (2.0 mL) at 0° C. The reaction mixture was stirred at 0° C. for 0.5 hours. N-Boc-N-methylethylenediamine (335 μL, 1.88 mmol) was added, the coolant removed and the reaction mixture stirred at ambient temperature overnight. The solvent was concentrated in vacuo and the crude product dissolved in DCM. The organic layer was washed with water, concentrated in vacuo (10 mL) and trifluoroacetic acid added (3.0 mL). The mixture was stirred at ambient temperature overnight, concentrated in vacuo and purified by ion-exchange chromatography (SCX-2 eluting with hydrochloric acid/MeOH→ammonia/MeOH). Further purification by flash-column chromatography (100% DCM→10% ammonia/MeOH/DCM) yielded the title compound as pale yellow solid (0.043 g, 25%).

1. customthe coolant removed
2. stirringthe reaction mixture stirred at ambient temperature overnight
3. concentrationThe solvent was concentrated in vacuo
4. dissolutionthe crude product dissolved in DCM
5. washThe organic layer was washed with water
6. concentrationconcentrated in vacuo (10 mL) and trifluoroacetic acid
7. additionadded (3.0 mL)
8. stirringThe mixture was stirred at ambient temperature overnight
9. concentrationconcentrated in vacuo
10. custompurified by ion-exchange chromatography (SCX-2 eluting with hydrochloric acid/MeOH→ammonia/MeOH)
11. customFurther purification by flash-column chromatography (100% DCM→10% ammonia/MeOH/DCM)

ORD record

ord-fb78232f45544c3cba80d15d5d3efede

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08486953B2