Sodium hydride → 2-(benzyloxy)-5-(cyclopropylmethyl)-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one

HRID 1396511Notes

Reaction equation

HRID 1396511 reaction equation
[H-].[Na+].[CH2:3]([O:10][C:11]1[CH:20]=[C:14]2[C:15](=[O:19])[NH:16][CH2:17][CH2:18][N:13]2[N:12]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Br[CH2:22][CH:23]1[CH2:25][CH2:24]1>CN(C=O)C.O>[CH2:3]([O:10][C:11]1[CH:20]=[C:14]2[C:15](=[O:19])[N:16]([CH2:22][CH:23]3[CH2:25][CH2:24]3)[CH2:17][CH2:18][N:13]2[N:12]=1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 81503BromomethylcyclopropaneHCID 727147872-(benzyloxy)-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one

Product 1

HCID 867065182-(benzyloxy)-5-(cyclopropylmethyl)-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-oneYield 78.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A 60% dispersion of sodium hydride in mineral oils (8.14 mg, 0.2 mmol) was added to a stirred solution of 2-(benzyloxy)-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one (0.045 g, 0.18 mmol) in DMF (2.7 mL) at 0° C. The mixture was stirred at 0° C. for 15 minutes. Then (bromomethyl)cyclopropane (22 μL, 0.22 mmol) was added at 0° C. The mixture was stirred at 0° C. for 1 hour and then allowed to warm to room temperature and stirred for 16 hours. The mixture was diluted with water and extracted with AcOEt. The organic layer was separated, washed with a saturated solution of NH4Cl, dried (Na2SO4), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 20/80). The desired fractions were collected, the solvents evaporated in vacuo and the residue was triturated with DIPE to yield 2-(benzyloxy)-5-(cyclopropylmethyl)-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one (42 mg, 76% yield) as a white solid. C17H19N3O2. 1H NMR (500 MHz, CDCl3) δ ppm 0.25-0.36 (m, 2H), 0.51-0.62 (m, 2H), 0.98-1.08 (m, 1H), 3.43 (d, J=6.9 Hz, 2H), 3.83 (dd, J=6.9, 5.5 Hz, 2H), 4.23 (dd, J=6.9, 5.5 Hz, 2H), 5.20 (s, 2H), 6.26 (s, 1H), 7.29-7.35 (m, 1H), 7.37 (t, J=7.4 Hz, 2H), 7.41-7.48 (m, 2H).

Workup

  1. stirringThe mixture was stirred at 0° C. for 1 hour
  2. temperatureto warm to room temperature
  3. stirringstirred for 16 hours
  4. extractionextracted with AcOEt
  5. customThe organic layer was separated
  6. washwashed with a saturated solution of NH4Cl
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. customthe solvents evaporated in vacuo
  10. customThe crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 20/80)
  11. customThe desired fractions were collected
  12. customthe solvents evaporated in vacuo
  13. customthe residue was triturated with DIPE

Sources & evidence

ORD record
ord-44bb82d3c42646f0851daca10365f1fe
Source dataset
uspto-grants-2014_12
Patent number
US08901125B2

Reaction notes

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