Methyl iodide → 1-(4-Benzyl-7,7-dimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin-3-yl)-2-methyl-2-(4-methylphenyl)-1-propanone

HRID 2108574Notes

Reaction equation

HRID 2108574 reaction equation
[CH:1](NC(C)C)(C)C.C([Li])CCC.[CH2:13]([N:20]1[CH:25]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:24][C:23]([CH3:33])([CH3:32])[N:22]2[N:34]=[CH:35][C:36]([C:37](=[O:47])[CH:38]([C:40]3[CH:45]=[CH:44][C:43]([CH3:46])=[CH:42][CH:41]=3)[CH3:39])=[C:21]12)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.IC>C1COCC1>[CH2:13]([N:20]1[CH:25]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:24][C:23]([CH3:33])([CH3:32])[N:22]2[N:34]=[CH:35][C:36]([C:37](=[O:47])[C:38]([CH3:1])([C:40]3[CH:45]=[CH:44][C:43]([CH3:46])=[CH:42][CH:41]=3)[CH3:39])=[C:21]12)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 7912DiisopropylamineHCID 576314041-(4-Benzyl-7,7-dimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin-3-yl)-2-(4-methylphenyl)-1-propanoneHCID 178418339Butyllithium

Product 1

HCID 576323091-(4-Benzyl-7,7-dimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin-3-yl)-2-methyl-2-(4-methylphenyl)-1-propanoneYield 23.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To 0.110 mL (0.785 mmol) of diisopropyl amine dissolved in 5 mL of THF at −78° C. was added 0.314 mL (0.785 mmol) of a 2.5 M solution of n-butyllithium in hexanes. After stirring for 30 min, 0.28 g (0.604 mmol) of 5 was added as a solution in 1 mL of THF. The reaction was stirred at room temperature for 1 h before 0.049 mL (0.79 mmol) of iodomethane was added as a solution in 1 mL of THF. After 1 h the reaction was quenched by addition of approximately 0.5 mL of saturated aqueous ammonium chloride, diluted with AcOEt and dried over sodium sulfate. Filtering the solution through a short plug of silica gel and concentrating in vacuo provided the crude product. Purification by flash chromatography eluting with 90% hexanes/AcOEt gave 0.067 g (23%) of the title compound as an off white solid. MS Calcd.: 477. Found: 478 (M+H).

Workup

  1. customAfter 1 h the reaction was quenched by addition of approximately 0.5 mL of saturated aqueous ammonium chloride
  2. additiondiluted with AcOEt
  3. dry with materialdried over sodium sulfate
  4. filtrationFiltering the solution through a short plug of silica gel
  5. concentrationconcentrating in vacuo
  6. customprovided the crude product
  7. customPurification by flash chromatography
  8. washeluting with 90% hexanes/AcOEt

Sources & evidence

ORD record
ord-453fdc76499a4369943ab001ab8c1da4
Source dataset
uspto-grants-2009_04
Patent number
US07514441B2

Reaction notes

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