Sodium Bicarbonate → HCID 178448144, compound

HRID 539046Notes

Reaction equation

HRID 539046 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:21]2[CH:22]=[N:23][N:24]3[CH:29]=[CH:28][C:27]([N:30]4[C@@H:34]([CH:35]([CH3:37])[CH3:36])[CH2:33][N:32]([CH:38]5[CH2:41][N:40](C(OC(C)(C)C)=O)[CH2:39]5)[C:31]4=[O:49])=[N:26][C:25]=23)[CH:5]=[CH:6][C:7]=1[C:8]1[N:12](COCC[Si](C)(C)C)[N:11]=[CH:10][N:9]=1.C([O-])(O)=O.[Na+]>CCO>[NH:40]1[CH2:41][CH:38]([N:32]2[CH2:33][C@H:34]([CH:35]([CH3:37])[CH3:36])[N:30]([C:27]3[CH:28]=[CH:29][N:24]4[N:23]=[CH:22][C:21]([C:4]5[CH:5]=[CH:6][C:7]([C:8]6[N:9]=[CH:10][NH:11][N:12]=6)=[C:2]([F:1])[CH:3]=5)=[C:25]4[N:26]=3)[C:31]2=[O:49])[CH2:39]1

Participants

4

Reactant 2

HCID 516892Sodium BicarbonateHCID 68089051HCID 68089051, compound

Product 1

HCID 178448144HCID 178448144, compoundYield 82%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of tert-butyl 3-((4S)-3-(3-(3-fluoro-4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-5-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyl-2-oxoimidazolidin-1-yl)azetidine-1-carboxylate (22 mg, 0.032 mmol) and 1:2 EtOH/6N aqueous HCl (1 mL) was heated at reflux for 2 hours. After cooling, the reaction mixture was basified by slow addition of saturated aqueous NaHCO3 solution. The mixture was extracted with 10% MeOH in DCM. The combined extracts were washed with brine, dried and concentrated. The residue was purified by column chromatography (20% 7N ammonia in MeOH/dichloromethane) to give (S)-1-(azetidin-3-yl)-3-(3-(3-fluoro-4-(1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropylimidazolidin-2-one (12 mg, 82%) as a pale yellow solid. LCMS (APCI+) m/z 462.2 [M+H]+.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 2 hours
  3. temperatureAfter cooling
  4. extractionThe mixture was extracted with 10% MeOH in DCM
  5. washThe combined extracts were washed with brine
  6. customdried
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography (20% 7N ammonia in MeOH/dichloromethane)

Sources & evidence

ORD record
ord-c99dc740f73f48da81d2e6d259b16505
Source dataset
uspto-grants-2014_10
Patent number
US08865726B2

Reaction notes

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