Sodium hydride → HCID 118114446, compound

(R)-tert-Butyl 3-aminopiperidine-1-carboxylate (1.28 g, 6.4 mmol) was dissolved in 15 mL dry THF. To it was added 3-chloropropyl isocyante (660 μL, 6.4 mmol), and the mixture was stirred at RT for 3 hours. To it was added NaH (60% in mineral oil, 310 mg, 7.68 mmol) and the mixture was stirred for overnight. Another batch of NaH (310 mg, 7.68 mmol) was then added to drive the cyclization to completion, The mixture was diluted with 200 mL EtOAc, washed with water, dried, concentrated and subjected to silica flash column using 0 to 5% MeOh in DCM to isolate (R)-tert-butyl 3-(2-oxotetrahydropyrimidin-1(2H)-yl)piperidine-1-carboxylate (408) (1.53 g, 84%) as a white solid. It was dissolved in 50 mL dry THF. To the solution was added NaH (440 mg, 10.80 mmol), and the mixture was stirred for 15 min at RT. Then iodomethane (680 μL, 10.80 mmol) was added, and it was stirred at RT for overnight. It was diluted with 200 mL EtOAc and 30 mL water. The organic phase was separated, washed with water, dried, concentrated and subjected to silica flash column with 0 to 4% MeOH in DCM to isolate (R)-tert-butyl 3-(3-methyl-2-oxotetrahydropyrimidin-1(2H)-yl)piperidine-1-carboxylate (409) (1.52 g, 95%) as a white solid. It was treated with 20 mL commercial 4N HCl in dioxane at RT for 30 min to yield (R)-1-methyl-3-(piperidin-3-yl)tetrahydropyrimidin-2(1H)-one hydrochloride (410) (1.27 g) as a white solid after evaporation in vacuo to dryness.

1. additionTo it was added 3-chloropropyl isocyante (660 μL, 6.4 mmol)
2. stirringthe mixture was stirred for overnight
3. washwashed with water
4. customdried
5. concentrationconcentrated

ORD record

ord-d491bf6e608e40cfb4ac7fc863690639

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09382246B2