Sodium hydride → HCID 58010260, compound

HRID 2204605Notes

Reaction equation

HRID 2204605 reaction equation
[H-].[Na+].[S:3]([N:13]1[C:17]2=[N:18][CH:19]=[C:20]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[N:21]=[C:16]2[CH:15]=[CH:14]1)([C:6]1[CH:12]=[CH:11][C:9]([CH3:10])=[CH:8][CH:7]=1)(=[O:5])=[O:4].Br[CH2:31][C:32]([CH:34]1[CH:39]([CH3:40])[CH2:38][CH2:37][N:36]([C:41]([O:43][CH2:44][C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)=[O:42])[CH2:35]1)=[O:33]>CN(C=O)C>[C:25]([O:24][C:23]([N:22]([C:20]1[N:21]=[C:16]2[CH:15]=[CH:14][N:13]([S:3]([C:6]3[CH:7]=[CH:8][C:9]([CH3:10])=[CH:11][CH:12]=3)(=[O:5])=[O:4])[C:17]2=[N:18][CH:19]=1)[CH2:31][C:32]([CH:34]1[CH:39]([CH3:40])[CH2:38][CH2:37][N:36]([C:41]([O:43][CH2:44][C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=2)=[O:42])[CH2:35]1)=[O:33])=[O:29])([CH3:26])([CH3:28])[CH3:27]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 580097831,1-Dimethylethyl N-(5-((4-methylphenyl)sulfonyl)-5H-pyrrolo(2,3-b)pyrazin-2-yl)carbamateHCID 58009834HCID 58009834, compound

Product 1

HCID 58010260HCID 58010260, compoundYield 100%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
0 °C

Procedure

To a suspension of NaH (60% dispersion in mineral oil, 0.088 g, 2.2 mmol) in DMF at about 0° C. (10 mL) was added a solution of tert-butyl 5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-ylcarbamate (0.86 g, 2.2 mmol, Step F) in DMF (10 mL) and the mixture was stirred at about 0° C. for about 1 h. A solution of benzyl 3-(2-bromoacetyl)-4-methylpiperidine-1-carboxylate (0.78 g, 2.2 mmol, Step B) in DMF (5 mL) was added drop-wise and the resulting mixture was stirred at ambient temperature for about 16 h. The solvent was removed and the residue was partitioned between EtOAc and water (40 mL each). The organic phase was washed with brine (20 mL), dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to give benzyl 3-(2-(tert-butoxycarbonyl(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)amino)acetyl)-4-methylpiperidine-1-carboxylate (1.45 g, 100%): LC/MS (Table 2, Method a) Rt=3.14 min; MS m/z: 662 (M+H)+.

Workup

  1. stirringthe resulting mixture was stirred at ambient temperature for about 16 h
  2. customThe solvent was removed
  3. customthe residue was partitioned between EtOAc and water (40 mL each)
  4. washThe organic phase was washed with brine (20 mL)
  5. dry with materialdried over anhydrous MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-189901bd416747828889d1f8facc4ef5
Source dataset
uspto-grants-2016_06
Patent number
US09365579B2

Reaction notes

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