Methanol → 4-Cyano-1H-imidazole-2-carboxylic acid [2-cyclohex-1-enyl-4-(2-methylsulfamoyl-ethyl)-phenyl]-amide

HRID 1190147Notes

Reaction equation

HRID 1190147 reaction equation
[C:1]1([C:7]2[CH:12]=[C:11]([CH2:13][CH2:14][S:15](=[O:19])(=[O:18])[NH:16][CH3:17])[CH:10]=[CH:9][C:8]=2[NH:20][C:21]([C:23]2[N:24](COCC[Si](C)(C)C)[CH:25]=[C:26]([C:28]#[N:29])[N:27]=2)=[O:22])[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1.CO.C(O)(C(F)(F)F)=O>C(Cl)Cl>[C:1]1([C:7]2[CH:12]=[C:11]([CH2:13][CH2:14][S:15](=[O:18])(=[O:19])[NH:16][CH3:17])[CH:10]=[CH:9][C:8]=2[NH:20][C:21]([C:23]2[NH:24][CH:25]=[C:26]([C:28]#[N:29])[N:27]=2)=[O:22])[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1

Participants

5

Reactant 3

HCID 887Methanol2×HCID 6422Trifluoroacetic acidHCID 589943644-Cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid [2-cyclohex-1-enyl-4-(2-methylsulfamoyl-ethyl)-phenyl]-amide

Product 1

HCID 1784862924-Cyano-1H-imidazole-2-carboxylic acid [2-cyclohex-1-enyl-4-(2-methylsulfamoyl-ethyl)-phenyl]-amideYield 11.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 177 mg (0.326 mmol) of 4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid [2-cyclohex-1-enyl-4-(2-methylsulfamoyl-ethyl)-phenyl]-amide (as prepared in the previous step) in CH2Cl2 (10 mL) was treated with MeOH (300 μL) and TFA (3 mL) at RT for 45 min. MeOH (10 mL) was added, and solvents were evaporated in vacuo. The solid residue was triturated with a minimum amount of acetonitrile with sonication, but further purification was needed. Silica gel chromatography of the solid with 50% EtOAc-hexane also afforded impure material. The solid was purified by RP-HPLC (C18) with 40-100% CH3CN in 0.1% TFA/H2O over 30 min to afford 14.9 mg (11%) of the title compound as a white solid: 1H-NMR (CD3CN; 400 MHz): δ 9.38 (s, 1H), 8.27-8.20 (m, 1H), 7.93 (s, 1H), 7.27-7.20 (m, 1H), 7.18-7.14 (m, 1H), 5.89-5.82 (m, 1H), 5.09-5.01 (m, 1H), 3.36-3.26 (m, 2H), 3.08-3.00 (m, 2H), 2.70 (d, 3H, J=5.2 Hz), 2.32-2.25 (m, 4H), 1.90-1.74 (m, 4H). Mass spectrum (ESI, m/z): Calcd. for C20H23N5O3S, 414.1 (M+H). found 414.1.

Workup

  1. customsolvents were evaporated in vacuo
  2. customThe solid residue was triturated with a minimum amount of acetonitrile with sonication, but further purification
  3. customThe solid was purified by RP-HPLC (C18) with 40-100% CH3CN in 0.1% TFA/H2O over 30 min

Sources & evidence

ORD record
ord-2930322c0a144139b83056aa2e074569
Source dataset
uspto-grants-2014_03
Patent number
US08674100B2

Reaction notes

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