Sodium Azide → tert-Butyl 4-(8-(2-chloro-4-fluorophenyl)-6-hydroxy-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-2-ylamino)piperidine-1-carboxylate

Temperature

100 °C

To a solution of tert-butyl 4-(((3SR,5SR)-3-(2-chloro-4-fluorophenyl)-5-hydroxy-2-oxopiperidin-1-ylimino)(methylthio)methylamino)piperidine-1-carboxylate (1.1 g, 2.1 mmol) in DMF (5.5 mL) was added sodium azide (0.2 g, 3.2 mmol) and the reaction heated to 100° C. for 48 hours. The reaction was then concentrated to dryness, redissolved in ethyl acetate, washed with water, brine, dried with sodium sulfate and the solvent was evaporated. The residue was redissolved in THF, trimethylphosphine added (2.1 mL, 1 M in toluene, 2.1 mmol) and the reaction heated to 160° C. in a micowave for 12 hours. The reaction was then concentrated in vacuo and the residue was purified by column chromatography on silica gel using ethyl acetate/MeOH (v/v 1:0 to 9:1) as eluent. The title compound was obtained as a light yellow foam (0.2 g, 20%), an inseparable 1:1 mixture of diasteriomers.

1. concentrationThe reaction was then concentrated to dryness
2. dissolutionredissolved in ethyl acetate
3. washwashed with water, brine
4. dry with materialdried with sodium sulfate
5. customthe solvent was evaporated
6. dissolutionThe residue was redissolved in THF
7. additiontrimethylphosphine added (2.1 mL, 1 M in toluene, 2.1 mmol)
8. temperaturethe reaction heated to 160° C. in a micowave for 12 hours
9. concentrationThe reaction was then concentrated in vacuo
10. customthe residue was purified by column chromatography on silica gel

ORD record

ord-d4dbab5f809149d28fdfd360e454dfe1

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08486967B2