(Diethylamino)sulfur trifluoride → (S)-6-fluoromethyl-5-(4-fluoro-phenyl)-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one

HRID 2046194Notes

Reaction equation

HRID 2046194 reaction equation
CCN(S(F)(F)[F:7])CC.[F:10][C:11]1[CH:16]=[CH:15][C:14]([N:17]2[C@H:22]([CH2:23]O)[CH2:21][N:20]3[N:25]=[C:26]([CH2:28][O:29][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)[CH:27]=[C:19]3[C:18]2=[O:36])=[CH:13][CH:12]=1>C(Cl)Cl>[F:7][CH2:23][C@@H:22]1[CH2:21][N:20]2[N:25]=[C:26]([CH2:28][O:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH:27]=[C:19]2[C:18](=[O:36])[N:17]1[C:14]1[CH:13]=[CH:12][C:11]([F:10])=[CH:16][CH:15]=1

Participants

4

Reactant 2

HCID 123472(Diethylamino)sulfur trifluorideHCID 67974066(S)-5-(4-fluoro-phenyl)-6-hydroxymethyl-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one

Product 1

HCID 67973947(S)-6-fluoromethyl-5-(4-fluoro-phenyl)-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-oneYield 60%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

DAST (0.067 mL, 0.55 mmol) was added to a solution of (S)-5-(4-fluoro-phenyl)-6-hydroxymethyl-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (135 mg, 0.37 mmol) in DCM (2 mL) at −10° C. The mixture was stirred at room temperature for 15 minutes. Then quenched with a 1N solution of HCl and extracted with AcOEt. The organic layer was separated, dried (Na2SO4), filtered and the solvent evaporated in vacuo. The residue was purified by flash column chromatography (silica; AcOEt in heptane 20/80 to 80/20). Desired fractions were collected and the solvents evaporated in vacuo. The residue was triturated with DIPE to yield (S)-6-fluoromethyl-5-(4-fluoro-phenyl)-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (81 mg, 60% yield) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ ppm 4.32-4.37 (m, 1H), 4.37-4.42 (m, 0.5H), 4.42-4.52 (m, 1H), 4.59 (dd, J=9.4, 4.5 Hz, 0.5H), 4.66-4.77 (m, 2H), 5.13 (s, 2H), 6.95-7.03 (m, 3H), 7.03 (s, 1H), 7.13-7.20 (m, 2H), 7.27-7.35 (m, 4H).

Workup

  1. customThen quenched with a 1N solution of HCl
  2. extractionextracted with AcOEt
  3. customThe organic layer was separated
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customthe solvent evaporated in vacuo
  7. customThe residue was purified by flash column chromatography (silica; AcOEt in heptane 20/80 to 80/20)
  8. customDesired fractions were collected
  9. customthe solvents evaporated in vacuo
  10. customThe residue was triturated with DIPE

Sources & evidence

ORD record
ord-75da510f1f924ff4bb6505ff273b3add
Source dataset
uspto-grants-2013_11
Patent number
US08592422B2

Reaction notes

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