Hydrochloric Acid → HCID 178448145, compound

HRID 539039Notes

Reaction equation

HRID 539039 reaction equation
[CH:1]([C@H:4]1[CH2:8][N:7]([CH2:9][CH:10]2[CH2:15][CH2:14][N:13](C(OC(C)(C)C)=O)[CH2:12][CH2:11]2)[C:6](=[O:23])[N:5]1[C:24]1[CH:29]=[CH:28][N:27]2[N:30]=[CH:31][C:32]([C:33]3[CH:38]=[CH:37][C:36]([C:39]4[N:43]=[CH:42][N:41](COCC[Si](C)(C)C)[N:40]=4)=[CH:35][CH:34]=3)=[C:26]2[N:25]=1)([CH3:3])[CH3:2].CCO.C([O-])(O)=O.[Na+].[ClH:60]>CCOCC>[ClH:60].[NH:41]1[CH:42]=[N:43][C:39]([C:36]2[CH:35]=[CH:34][C:33]([C:32]3[CH:31]=[N:30][N:27]4[CH:28]=[CH:29][C:24]([N:5]5[C@@H:4]([CH:1]([CH3:3])[CH3:2])[CH2:8][N:7]([CH2:9][CH:10]6[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]6)[C:6]5=[O:23])=[N:25][C:26]=34)=[CH:38][CH:37]=2)=[N:40]1

Participants

6

Reactant 4

HCID 313Hydrochloric Acid2×HCID 702EthanolHCID 516892Sodium BicarbonateHCID 67034460(S)-tert-butyl 4-((4-isopropyl-2-oxo-3-(3-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)imidazolidin-1-yl)methyl)piperidine-1-carboxylate

Product 1

HCID 178448145HCID 178448145, compound

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

A mixture of (S)-tert-butyl 4-((4-isopropyl-2-oxo-3-(3-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)imidazolidin-1-yl)methyl)piperidine-1-carboxylate (99 mg, 0.14 mmol) and EtOH/6N aqueous HCl (1:2, 2 mL total) was heated at reflux for 2 hours. After cooling, the reaction mixture was neutralized by slow addition of saturated aqueous NaHCO3 solution. The mixture was extracted with 10% THF in dichloromethane. 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 the free base, which was converted to HCl salt (38 mg, 53%) by treatment with 2N HCl in ether. LCMS (APCI+) m/z 486.8 [M+H]+.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 2 hours
  3. temperatureAfter cooling
  4. extractionThe mixture was extracted with 10% THF in dichloromethane
  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)
  9. customto give the free base, which

Sources & evidence

ORD record
ord-4c5e3a740b64407f980973eaa6454d49
Source dataset
uspto-grants-2014_10
Patent number
US08865726B2

Reaction notes

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