Hydrochloric Acid → HCID 178433214, compound

HRID 241460Notes

Reaction equation

HRID 241460 reaction equation
Cl.[F:2][CH:3]([F:38])[C:4]1[N:9]=[CH:8][C:7]([CH2:10][NH:11]C(=O)OC(C)(C)C)=[CH:6][C:5]=1[C:19](=[O:37])[NH:20][C:21]1[NH:22][C:23]([C:27]2[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:29][CH:28]=2)=[C:24]([CH3:26])[N:25]=1>O>[NH2:11][CH2:10][C:7]1[CH:6]=[C:5]([C:19]([NH:20][C:21]2[NH:22][C:23]([C:27]3[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:29][CH:28]=3)=[C:24]([CH3:26])[N:25]=2)=[O:37])[C:4]([CH:3]([F:38])[F:2])=[N:9][CH:8]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 178433216HCID 178433216, compound

Product 1

HCID 178433214HCID 178433214, compoundYield 57.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Add hydrochloric acid (10 mL, 40.0 mmol, 4 M in 1,4 dioxane) to tert-butyl N-[[6-(difluoromethyl)-5-[[4-methyl-5-[4-(trifluoromethyl)phenyl]-1H-imidazol-2-yl]carbamoyl]-3-pyridyl]methyl]carbamate (0.212 g, 0.403 mmol) and stir overnight. Dilute with water, and extract with Et2O. Adjust the pH to ˜8 with a saturated sodium bicarbonate aqueous solution. Extract with EtOAc (3×30 mL). Dry the organic extracts over sodium sulfate; filter; collect the filtrate; and concentrate the filtrate under reduced pressure. Purify by reverse phase flash chromatography (Analogix® 40 g @ 40 mL/min) eluting with a gradient of 2-55% ACN/water over 30 minutes. Concentrate the appropriate fractions under reduced pressure until all the ACN is removed and only water remains. Add a saturated sodium bicarbonate aqueous solution (30 mL), and extract with EtOAc (3×20 mL). Dry the organic extracts over sodium sulfate; filter; collect the filtrate; and concentrate the filtrate under reduced pressure to give the title compound as a light yellow solid (0.098 g, 57% yield). 1H NMR (400.43 MHz, d6-DMSO) δ 8.71-8.69 (m, 1H), 8.16 (s, 1H), 7.79-7.77 (m, 2H), 7.69-7.67 (m, 2H), 7.42-7.28 (m, 1H), 3.81 (s, 2H), 2.43 (s, 3H).

Workup

  1. extractionextract with Et2O
  2. extractionExtract with EtOAc (3×30 mL)
  3. dry with materialDry the organic extracts over sodium sulfate
  4. filtrationfilter
  5. customcollect the filtrate
  6. concentrationand concentrate the filtrate under reduced pressure
  7. customPurify by reverse phase flash chromatography (Analogix® 40 g @ 40 mL/min)
  8. washeluting with a gradient of 2-55% ACN/water over 30 minutes
  9. concentrationConcentrate the appropriate fractions under reduced pressure until all the ACN
  10. customis removed
  11. additionAdd a saturated sodium bicarbonate aqueous solution (30 mL)
  12. extractionextract with EtOAc (3×20 mL)
  13. dry with materialDry the organic extracts over sodium sulfate
  14. filtrationfilter
  15. customcollect the filtrate
  16. concentrationand concentrate the filtrate under reduced pressure

Sources & evidence

ORD record
ord-8d6a6d08ac0944e880dbe355f772eb6e
Source dataset
uspto-grants-2014_02
Patent number
US08648200B2

Reaction notes

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