(Diethylamino)sulfur trifluoride → HCID 67973808, compound

HRID 2046198Notes

Reaction equation

HRID 2046198 reaction equation
CCN(S(F)(F)[F:7])CC.O[CH:11]([CH3:31])[CH2:12][N:13]1[CH2:18][CH2:17][N:16]2[N:19]=[C:20]([CH2:22][O:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH:21]=[C:15]2[C:14]1=[O:30]>C(Cl)Cl>[F:7][CH:11]([CH3:31])[CH2:12][N:13]1[CH2:18][CH2:17][N:16]2[N:19]=[C:20]([CH2:22][O:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH:21]=[C:15]2[C:14]1=[O:30]

Participants

4

Reactant 2

HCID 123472(Diethylamino)sulfur trifluorideHCID 67974700HCID 67974700, compound

Product 1

HCID 67973808HCID 67973808, compoundYield 29%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

DAST (0.02 mL, 0.15 mmol) was added dropwise to a solution of (rac)-5-(2-hydroxy-propyl)-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (30 mg, 0.1 mmol) in DCM (0.6 mL) at 0° C. The mixture was then allowed to warm to room temperature and stirred at 100° C. for 10 minutes under microwave irradiation. The mixture was quenched with a saturated solution of NaHCO3 and extracted with DCM. 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 0/100 to 100/0). Desired fractions were collected and solvents evaporated in vacuo. The product was repurified by RP HPLC on (C18 XBridge 30×100 5 um). Mobile phase (Gradient from 80% 0.1% NH4CO3H/NH4OH pH 9 solution in H2O, 20% ACN to 0% 0.1% NH4CO3H/NH4OH pH 9 solution in H2O, 100% ACN) and triturated with DIPE to yield (rac)-5-(2-fluoro-propyl)-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (8.3 mg, 29% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 1.38 (dd, J=24.0, 6.5 Hz, 3H), 3.42 (ddd, J=20.1, 14.6, 7.6 Hz, 1H), 3.80-3.91 (m, 1H), 3.91-4.08 (m, 2H), 4.33-4.46 (m, 2H), 4.83-5.05 (m, 1H), 5.10 (s, 2H), 6.90-6.95 (m, 1H), 6.95-7.03 (m, 3H), 7.27-7.33 (m, 2H).

Workup

  1. customThe mixture was quenched with a saturated solution of NaHCO3
  2. extractionextracted with DCM
  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 0/100 to 100/0)
  8. customDesired fractions were collected
  9. customsolvents evaporated in vacuo
  10. customThe product was repurified by RP HPLC on (C18 XBridge 30×100 5 um)
  11. customMobile phase (Gradient from 80% 0.1% NH4CO3H/NH4OH pH 9 solution in H2O, 20% ACN to 0% 0.1% NH4CO3H/NH4OH pH 9 solution in H2O, 100% ACN) and triturated with DIPE

Sources & evidence

ORD record
ord-9dfa80842c8d4c76ae6f3df4ba44212e
Source dataset
uspto-grants-2013_11
Patent number
US08592422B2

Reaction notes

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