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

HRID 451524Notes

Reaction equation

HRID 451524 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[CH2:14][CH:13]([OH:15])[CH2:12][N:11]([N:16]=[C:17]([NH:20][CH:21]2[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]2)SC)[C:10]1=O.[N-:35]=[N+]=[N-].[Na+]>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[CH2:14][CH:13]([OH:15])[CH2:12][N:11]2[N:16]=[C:17]([NH:20][CH:21]3[CH2:22][CH2:23][N:24]([C:27]([O:29][C:30]([CH3:31])([CH3:33])[CH3:32])=[O:28])[CH2:25][CH2:26]3)[N:35]=[C:10]12

Participants

4

Reactant 2

HCID 33557Sodium AzideHCID 178503960tert-Butyl 4-(((3SR,5SR)-3-(2-chloro-4-fluorophenyl)-5-hydroxy-2-oxopiperidin-1-ylimino)(methylthio)methylamino)piperidine-1-carboxylate

Product 1

HCID 67345513tert-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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-d4dbab5f809149d28fdfd360e454dfe1
Source dataset
uspto-grants-2013_07
Patent number
US08486967B2

Reaction notes

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