Hydrochloric Acid → N-((1,3-dimethyl-1H-pyrazol-4-yl)methyl)-1-(4-fluorophenyl)-2-mercapto-N-methyl-1H-imidazole-5-carboxamide

HRID 2368472Notes

Reaction equation

HRID 2368472 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([C:13]([OH:15])=O)=[CH:11][N:10]=[C:9]2[S:16]C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=[CH:4][CH:3]=1.[CH3:36][N:37]1[CH:41]=[C:40]([CH2:42][NH:43][CH3:44])[C:39]([CH3:45])=[N:38]1.C(N(CC)CC)C.CCCP(=O)=O.Cl.C(=O)(O)[O-].[Na+]>ClCCl>[CH3:36][N:37]1[CH:41]=[C:40]([CH2:42][N:43]([CH3:44])[C:13]([C:12]2[N:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)[C:9]([SH:16])=[N:10][CH:11]=2)=[O:15])[C:39]([CH3:45])=[N:38]1

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 70102001-(1,3-dimethyl-1H-pyrazol-4-yl)-N-methylmethanamineHCID 16167369Propylphosphoric anhydrideHCID 711174681-(4-fluorophenyl)-2-(tritylthio)-1H-imidazole-5-carboxylic acid

Product 1

HCID 178434002N-((1,3-dimethyl-1H-pyrazol-4-yl)methyl)-1-(4-fluorophenyl)-2-mercapto-N-methyl-1H-imidazole-5-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 1-(4-fluorophenyl)-2-(tritylthio)-1H-imidazole-5-carboxylic acid (6) (3.24 g, 6.74 mmol), 1-(1,3-dimethyl-1H-pyrazol-4-yl)-N-methylmethanamine (0.95 g, 6.80 mmol), triethylamine (5.70 mL, 40.9 mmol) and propylphosphonic anhydride (T-3-P)(50% in ethyl acetate, 4.85 mL, 8.15 mmol) in dichloromethane (50 mL) was stirred overnight at room temperature. To the reaction 6N HCl (10 mL) was carefully added and was stirred at room temperature for 40 minutes. The solution was basified with saturated sodium bicarbonate and was extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (0-20% MeOH in dichloromethane) to afford N-((1,3-dimethyl-1H-pyrazol-4-yl)methyl)-1-(4-fluorophenyl)-2-mercapto-N-methyl-1H-imidazole-5-carboxamide

Workup

  1. additionwas carefully added
  2. extractionwas extracted with ethyl acetate
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash column chromatography on silica gel (0-20% MeOH in dichloromethane)

Sources & evidence

ORD record
ord-3620f747981c4daa96246c81b3abe3f8
Source dataset
uspto-grants-2014_04
Patent number
US08703776B2

Reaction notes

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