Lithium Hexamethyldisilazide → HCID 57504307, compound

HRID 1097985Notes

Reaction equation

HRID 1097985 reaction equation
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[OH:11][CH:12]([CH:23]([CH3:25])[CH3:24])[C:13]([NH:15][C:16]1[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][N:17]=1)=[O:14].Cl[C:27]1[N:32]=[CH:31][N:30]=[C:29]2[N:33]([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=3[Cl:42])[N:34]=[CH:35][C:28]=12>C1COCC1.CCOC(C)=O>[Cl:42][C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=1[N:33]1[C:29]2=[N:30][CH:31]=[N:32][C:27]([O:11][CH:12]([CH:23]([CH3:25])[CH3:24])[C:13]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][N:17]=3)=[O:14])=[C:28]2[CH:35]=[N:34]1

Participants

6

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 112655704-Chloro-1-(2-chlorophenyl)-1H-pyrazolo[3,4-D]pyrimidineHCID 574386132-hydroxy-3-methyl-N-(5-methylpyridin-2-yl)butanamide

Product 1

HCID 57504307HCID 57504307, compoundYield 73.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of LHMDS (0.999 mL, 1.00 mmol) in anhydrous THF (15 mL) was added dropwise to a stirred solution of racemic 2-hydroxy-3-methyl-N-(5-methylpyridin-2-yl)butanamide C1 (208 mg, 1.00 mmol) in anhydrous THF (15 mL) over a period of 3 minutes under nitrogen. The resulting suspension was stirred at ambient temperature for 10 minutes, then a solution of 4-chloro-1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidine B1 (265 mg, 1.00 mmol) in anhydrous THF (3 mL) was added dropwise over 1 minute and the resulting mixture heated to 50° C. for 3 hours. The mixture was allowed to cool to room temperature then diluted with EtOAc (50 mL), and washed sequentially with water (2×25 mL) and saturated brine (25 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The material was purified by flash silica chromatography, elution gradient 30 to 50% EtOAc in DCM. Pure fractions were evaporated to dryness to afford 2-(1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-methyl-N-(5-methylpyridin-2-yl)butanamide (320 mg).

Workup

  1. temperaturethe resulting mixture heated to 50° C. for 3 hours
  2. temperatureto cool to room temperature
  3. washwashed sequentially with water (2×25 mL) and saturated brine (25 mL)
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customto afford crude product
  8. customThe material was purified by flash silica chromatography, elution gradient 30 to 50% EtOAc in DCM
  9. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-0a917ed5169e453a8348fd5b5bed07b8
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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