Benzyl Bromide → 4-Benzyl-7,7-dimethyl-3-((4-methylbenzyl)sulfonyl)-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine

HRID 2108578Notes

Reaction equation

HRID 2108578 reaction equation
[CH3:1][C:2]1([CH3:28])[N:7]2[N:8]=[CH:9][C:10]([S:11]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=3)(=[O:13])=[O:12])=[C:6]2[NH:5][CH:4]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:3]1.[CH2:29](Br)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.[H-].[Na+]>C1COCC1.O>[CH2:29]([N:5]1[CH:4]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:3][C:2]([CH3:28])([CH3:1])[N:7]2[N:8]=[CH:9][C:10]([S:11]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=3)(=[O:12])=[O:13])=[C:6]12)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

6

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 136367712HCID 136367712, compound

Product 1

HCID 688643724-Benzyl-7,7-dimethyl-3-((4-methylbenzyl)sulfonyl)-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidineYield 93.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 0.34 g (0.86 mmol) of 5 in 10 mL of THF at 0° C. was added 0.128 mL (1.07 mmol) of benzyl bromide followed by 0.034 g (0.86 mmol) of sodium hydride (60% dispersion in mineral oil). The reaction was allowed to warm to room temperature after 30 min and stirred for an additional 30 min before being quenched with water. The quenched reaction was diluted with five volumes of water and extracted with AcOEt. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by flash chromatography eluting with 70% hexanes/AcOEt to give 0.39 g (93%) of the title compound as a white solid. 1H NMR (CDCl3) δ 1.27 (s, 3H), 1.52 (s, 3H), 1.93-2.05 (m, 2H), 2.27 (s, 3H), 3.83 (d, J=15.8 Hz, 1H), 4.18-4.30 (m, 3H), 5.51 (d, J=15.8 Hz, 1H), 6.98-7.00 (m, 2H), 7.09 (dd, J=8.2, 12.1 Hz, 4H), 7.17 (d, J=6.8 Hz, 2H), 7.26-7.30 (m, 3H), 7.32-7.40 (m, 3H), 7.47 (s, 1H)

Workup

  1. custombefore being quenched with water
  2. customThe quenched reaction
  3. extractionextracted with AcOEt
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by flash chromatography
  9. washeluting with 70% hexanes/AcOEt

Sources & evidence

ORD record
ord-005fdd401ec9400fad4a274ded281ffd
Source dataset
uspto-grants-2009_04
Patent number
US07514441B2

Reaction notes

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