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 63764Notes

Reaction equation

HRID 63764 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-586e2018fcc5423ebb90167e22395be3
Source dataset
uspto-grants-2016_09
Patent number
US09447100B2

Reaction notes

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