Hydrochloric Acid → HCID 59392685, compound

HRID 216738Notes

Reaction equation

HRID 216738 reaction equation
Cl.CCO.C(OC([N:12]1[CH2:17][CH2:16][CH:15]([N:18]2[C:22]([CH3:23])=[C:21]([C:24]3[CH:33]=[N:32][C:31]4[C:26](=[C:27]([C:34]5[CH:39]=[C:38]([F:40])[C:37]([CH2:41][N:42]6[CH2:47][CH2:46][O:45][CH2:44][CH2:43]6)=[C:36]([F:48])[CH:35]=5)[CH:28]=[CH:29][CH:30]=4)[N:25]=3)[CH:20]=[N:19]2)[CH2:14][CH2:13]1)=O)(C)(C)C>>[F:40][C:38]1[CH:39]=[C:34]([C:27]2[CH:28]=[CH:29][CH:30]=[C:31]3[C:26]=2[N:25]=[C:24]([C:21]2[CH:20]=[N:19][N:18]([CH:15]4[CH2:16][CH2:17][NH:12][CH2:13][CH2:14]4)[C:22]=2[CH3:23])[CH:33]=[N:32]3)[CH:35]=[C:36]([F:48])[C:37]=1[CH2:41][N:42]1[CH2:47][CH2:46][O:45][CH2:44][CH2:43]1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 702EthanolHCID 59392763HCID 59392763, compound

Product 1

HCID 59392685HCID 59392685, compound

Conditions

Temperature
60 °C

Procedure

A 1.25 M solution of HCl in EtOH (5 ml, 6.26 mmol) is added to 4-{4-[8-(3,5-Difluoro-4-morpholin-4-ylmethyl-phenyl)-quinoxalin-2-yl]-5-methyl-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester (Example 121, 239 mg, 0.368 mmol) and the reaction mixture is heated at 60° C. for 4 h. After cooling, the yellow suspension is concentrated under vacuo and the residue is diluted with EtOAc, poured onto a saturated solution of NaHCO3 and extracted 3× with EtOAc. The combined organic layers are washed with NaHCO3, brine, dried over Na2SO4, filtered and the filtrate is concentrated in vacuo. The residue is dissolved in CH2Cl2 and purified by chromatography on a 40 g silica gel column on a Combiflash Companion™ (Isco Inc.) apparatus (gradient CH2Cl2/(CH2Cl2:EtOH:NH3 85:13.5:1.5) from 1:0=>1:9) to afford the title compound as a pale orange foam. Rt=0.703 min (Acquity HPLC BEH C18, 2.1×50 mm, 1.7 micron, detection 215 nM, 0.1 min 2% CH3CN in H2O, 2% to 100% CH3CN in H2O in 1.5 min, 0.4 min 100% CH3CN+0.1% TFA, flow rate 1.0 ml/min); MS: 505 (M+1)+

Workup

  1. temperatureAfter cooling
  2. concentrationthe yellow suspension is concentrated under vacuo
  3. additionthe residue is diluted with EtOAc
  4. additionpoured onto a saturated solution of NaHCO3
  5. extractionextracted 3× with EtOAc
  6. washThe combined organic layers are washed with NaHCO3, brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationthe filtrate is concentrated in vacuo
  10. dissolutionThe residue is dissolved in CH2Cl2
  11. custompurified by chromatography on a 40 g silica gel column on a Combiflash Companion™ (Isco Inc.) apparatus (gradient CH2Cl2/(CH2Cl2:EtOH:NH3 85:13.5:1.5) from 1:0=>1:9)

Sources & evidence

ORD record
ord-b8bedf4dfc7a4dbea7f3aedc24715881
Source dataset
uspto-grants-2012_06
Patent number
US08193189B2

Reaction notes

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