Sodium hydride → Tert-butyl 4-(6-chloropyrido[3,2-d]pyrimidin-4-yloxy)piperidine-1-carboxylate

Temperature

0 °C

To a solution of tert-butyl 4-hydroxypiperidine-1-carboxylate (0.201 g, 1.000 mmol) in DMF (5.00 ml) was added NaH (0.052 g, 55% dispersion in mineral oil, 1.20 mmol) at 0° C. After stiffing for 30 min at room temperature, the reaction mixture was cooled to 0° C. and 4,6-dichloropyrido[3,2-d]pyrimidine (Intermediate 1, step D) (0.2 g, 1.000 mmol) was added to the mixture. After stiffing for 3 hours at room temperature, the reaction mixture was diluted with water, and extracted with EtOAc. The organic layers were dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (Hex:EtOAc=5:1) to give tert-butyl 4-(6-chloropyrido[3,2-d]pyrimidin-4-yloxy)piperidine-1-carboxylate (0.236 g, 65%) as a white solid. 1H-NMR (CDCl3, Varian 400 MHz) δ 1.49 (9H, s), 1.91-1.99 (2H, m), 2.10-2.13 (2H, m), 3.21-3.27 (2H, m), 3.83-3.97 (2H, m), 5.55-5.62 (1H, m), 7.74 (1H, d, J=8.8 Hz), 8.19 (1H, d, J=8.8 Hz), 8.41 (1H, s).

1. waitAfter stiffing for 3 hours at room temperature
2. extractionextracted with EtOAc
3. dry with materialThe organic layers were dried over MgSO4
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe residue was purified by column chromatography on SiO2 (Hex:EtOAc=5:1)

ORD record

ord-dbe14cc5e25e4770a9d325bae5008200

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08664230B2