Ethanol → 4-Cyano-1H-imidazole-2-carboxylic acid [2-(4,4-dimethyl-cyclohex-1-enyl)-4-(2-sulfamoyl-ethyl)-phenyl]-amide

HRID 1711287Notes

Reaction equation

HRID 1711287 reaction equation
C([NH:5][S:6]([CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]2[N:21](COCC[Si](C)(C)C)[CH:22]=[C:23]([C:25]#[N:26])[N:24]=2)=[O:19])=[C:13]([C:35]2[CH2:40][CH2:39][C:38]([CH3:42])([CH3:41])[CH2:37][CH:36]=2)[CH:12]=1)(=[O:8])=[O:7])(C)(C)C.CCO.C1(OC)C=CC=CC=1.C(O)(C(F)(F)F)=O>C(Cl)Cl.CO>[CH3:41][C:38]1([CH3:42])[CH2:39][CH2:40][C:35]([C:13]2[CH:12]=[C:11]([CH2:10][CH2:9][S:6](=[O:7])(=[O:8])[NH2:5])[CH:16]=[CH:15][C:14]=2[NH:17][C:18]([C:20]2[NH:21][CH:22]=[C:23]([C:25]#[N:26])[N:24]=2)=[O:19])=[CH:36][CH2:37]1

Participants

7

Reactant 4

HCID 702EthanolHCID 6422Trifluoroacetic acid2×HCID 7519AnisoleHCID 587548524-Cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid [4-(2-(tert-butylsulfamoyl)-ethyl)-2-(4,4-dimethyl-cyclohex-1-enyl)-phenyl]-amide

Product 1

HCID 1784245294-Cyano-1H-imidazole-2-carboxylic acid [2-(4,4-dimethyl-cyclohex-1-enyl)-4-(2-sulfamoyl-ethyl)-phenyl]-amideYield 32.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 311 mg (0.506 mmol) of 4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid [4-(2-tert-butylsulfamoyl-ethyl)-2-(4,4-dimethyl-cyclohex-1-enyl)-phenyl]-amide (as prepared in the previous step) in CH2Cl2 (6 mL) was treated with EtOH (175 μL), anisole (80.0 μL), and TFA (1.8 mL). Additional TFA (0.5 mL each) was added at 3.5 and at 26 h. The mixture stirred at RT for a total of 48 h. MeOH (3 mL) was added, the mixture was concentrated in vacuo, and the residue was purified by RP-HPLC (C18) with 20-100% CH3CN in 0.1% TFA/H2O over 30 min to afford 70.5 mg (32%) of the title compound as a white solid: 1H-NMR (CD3OD; 400 MHz): δ 8.17 (d, 1H, J=8.0 Hz), 8.01 (s, 1H), 7.21 (dd, 1H, J=8.0, 2.0 Hz), 7.13 (d, 1H, J=2.0 Hz), 5.79-5.73 (m, 1H), 3.40-3.34 (m, 1H), 3.16-3.07 (m, 2H), 2.37-2.29 (m, 2H), 2.13-2.07 (m, 2H), 1.65-1.57 (m, 2H), 1.10 (s, 6H). Mass spectrum (ESI, m/z): Calcd. for C21H25N5O3S, 428.2 (M+H), found 428.1.

Workup

  1. concentrationthe mixture was concentrated in vacuo
  2. customthe residue was purified by RP-HPLC (C18) with 20-100% CH3CN in 0.1% TFA/H2O over 30 min

Sources & evidence

ORD record
ord-12792308ff43459a8e3df2aac5385fca
Source dataset
uspto-grants-2010_09
Patent number
US07790724B2

Reaction notes

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