Sodium hydride → HCID 58382017, compound

HRID 1628102Notes

Reaction equation

HRID 1628102 reaction equation
[CH3:1][C:2]1[N:6]2[C:7]3[CH:13]=[CH:12][NH:11][C:8]=3[N:9]=[CH:10][C:5]2=[C:4]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([OH:23])([CH3:22])[CH3:21])=[CH:16][CH:15]=2)[N:3]=1.[H-].[Na+].[CH3:26][CH:27]([Si:29](Cl)([CH:33]([CH3:35])[CH3:34])[CH:30]([CH3:32])[CH3:31])[CH3:28]>C1COCC1>[CH3:1][C:2]1[N:6]2[C:7]3[CH:13]=[CH:12][N:11]([Si:29]([CH:33]([CH3:35])[CH3:34])([CH:30]([CH3:32])[CH3:31])[CH:27]([CH3:28])[CH3:26])[C:8]=3[N:9]=[CH:10][C:5]2=[C:4]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([OH:23])([CH3:21])[CH3:22])=[CH:16][CH:15]=2)[N:3]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 139400Triisopropylsilyl chlorideHCID 58382192HCID 58382192, compound

Product 1

HCID 58382017HCID 58382017, compoundYield 96.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

To a solution of 2-(4-(1-methyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-3-yl)phenyl)propan-2-ol (1.03 g, 3.36 mmol; Example #N.1.50) in THF (32 ml) at about −20° C. was added NaH (0.148 g, 3.70 mmol). The mixture was allowed to stir at about −20° C. for about 20 min. TIPSCl (0.790 ml, 3.70 mmol) was added and the resulting solution was allowed to stir at about −20° C. for about 1 h. The mixture was treated with 15 mL of an ice cold saturated aqueous NaCl solution and the resulting mixture was partitioned between EtOAc (100 mL) and water (50 mL). The layers were separated and the aqueous phase was extracted with EtOAc (3×25 mL). The combined organic phases were washed with saturated aqueous NaCl solution (100 mL), dried over Na2SO4, filtered, and concentrated in vacuo to give 2-(4-(1-methyl-6-(triisopropylsilyl)-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-3-yl)phenyl)propan-2-ol (1.5 g, 96%). LC/MS (Table 2, Method h) Rt=2.28 min; MS m/z 463 (M+H)+.

Workup

  1. stirringto stir at about −20° C. for about 1 h
  2. customthe resulting mixture was partitioned between EtOAc (100 mL) and water (50 mL)
  3. customThe layers were separated
  4. extractionthe aqueous phase was extracted with EtOAc (3×25 mL)
  5. washThe combined organic phases were washed with saturated aqueous NaCl solution (100 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1d439533966742b2bba3efbc615fab73
Source dataset
uspto-grants-2014_07
Patent number
US08785639B2

Reaction notes

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