Water → HCID 118906722, compound

HRID 919569Notes

Reaction equation

HRID 919569 reaction equation
[S:1]([N:11]1[C:15]2[N:16]=[CH:17][N:18]=[C:19]([NH:20][C@@H:21]3[CH2:26][CH2:25][CH2:24][N:23]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:22]3)[C:14]=2[CH:13]=[CH:12]1)([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2].[H-].[Na+].[CH2:36](Br)[CH:37]=[CH2:38].O>CN(C=O)C>[CH2:38]([N:20]([C:19]1[C:14]2[CH:13]=[CH:12][N:11]([S:1]([C:4]3[CH:5]=[CH:6][C:7]([CH3:8])=[CH:9][CH:10]=3)(=[O:3])=[O:2])[C:15]=2[N:16]=[CH:17][N:18]=1)[C@@H:21]1[CH2:26][CH2:25][CH2:24][N:23]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:22]1)[CH:37]=[CH2:36]

Participants

6

Reactant 4

HCID 962WaterHCID 7841Allyl bromideHCID 24758Sodium hydrideHCID 69676524HCID 69676524, compound

Product 1

HCID 118906722HCID 118906722, compoundYield 83.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (R)-tert-butyl 3-(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)piperidine-1-carboxylate (1.0 g, 2.1 mmol) in DMF (5 mL), NaH (60% suspension in mineral oil, 100 mg, 2.5 mmol) was added at 0° C. and the reaction mixture was stirred for 1 h. To the reaction mixture was added allyl bromide (308 mg, 2.12 mmol) and the reaction mixture was stirred for 6 h. The solution was diluted with ice-cooled water and stirred for 15 min, the solution was then extracted with EtOAc, dried over Na2SO4 and concentrated in vacuo to give the crude product that was purified by column chromatography (silica gel, gradient, EtOAc in hexanes) to give (0.9 g, 83%) of the titled compound. 1H NMR (400 MHz, CDCl3): δ 8.42 (s, 1H), 8.06 (d, J=8.0 Hz, 2H), 7.43 (d, J=3.2 Hz, 1H), 7.31 (d, J=8.0 Hz, 2H), 6.57 (d, J=3.2 Hz, 1H), 5.98-5.90 (m, 1H), 5.26-5.19 (m, 2H), 4.62-4.51 (m, 1H), 4.29-4.09 (m, 4H), 2.85 (t, J=11.6 Hz, 1H), 2.68-2.60 (m, 1H), 2.41 (s, 3H), 1.97-1.93 (m, 1H), 1.83-1.72 (m, 2H), 1.65-1.58 (m, 1H), 1.42 (s, 9H). LCMS [M+1]: 512.

Workup

  1. stirringthe reaction mixture was stirred for 6 h
  2. additionThe solution was diluted with ice-
  3. stirringstirred for 15 min
  4. extractionthe solution was then extracted with EtOAc
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customto give the crude product that
  8. customwas purified by column chromatography (silica gel, gradient, EtOAc in hexanes)

Sources & evidence

ORD record
ord-e9fa24eb23204e00a50306f80a5d7f71
Source dataset
uspto-grants-2016_03
Patent number
US09273028B2

Reaction notes

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