Aluminium lithium hydride → 5-Benzyl-2-(4-fluorophenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine

HRID 920708Notes

Reaction equation

HRID 920708 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]2[N:14]=[C:15]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[CH:16]=[C:10]2[C:9]1=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]2[N:14]=[C:15]([C:17]3[CH:18]=[CH:19][C:20]([F:23])=[CH:21][CH:22]=3)[CH:16]=[C:10]2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 1180612625-Benzyl-2-(4-fluorophenyl)-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one

Product 1

HCID 1180613795-Benzyl-2-(4-fluorophenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazineYield 77.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of Intermediate 1D (23.00 g, 71.6 mmol) in THF (230 mL) under N2 at −10° C. was added LAH (59.6 mL, 2.4 M solution in THF, 143 mmol). Reaction mixture was allowed to stir at room temperature for 12 h. Reaction mixture was quenched with ice-cold water and filtered through CELITE® pad and the filtrate was extracted with chloroform (3×150 mL) The combined organic layer was washed with brine, dried over Na2SO4, filtered and concentrated. The residue was triturated with diethyl ether (2×150 mL) and the resulting solid was filtered, rinsed with diethyl ether and dried to afford Intermediate 1E (17 g, 77%). MS(ES): m/z=308 [M+H]+; 1H NMR (300 MHz, CDCl3) δ ppm 7.67-7.82 (m, 2H), 7.31-7.47 (m, 514), 7.01-7.14 (m, 2H), 6.19 (s, 1H), 4.22 (t, J=4.2 Hz, 2H), 3.73 (s, 2H), 3.70 (s, 2H), 2.97 (t, J=5.6 Hz, 2H).

Workup

  1. customReaction mixture
  2. customReaction mixture
  3. customwas quenched with ice-cold water
  4. filtrationfiltered through CELITE® pad
  5. extractionthe filtrate was extracted with chloroform (3×150 mL) The combined organic layer
  6. washwas washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was triturated with diethyl ether (2×150 mL)
  11. filtrationthe resulting solid was filtered
  12. washrinsed with diethyl ether
  13. customdried

Sources & evidence

ORD record
ord-67b6d480956a49cd9835b13f9751311e
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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