Trifluoroacetic acid → 4-Cyano-1H-imidazole-2-carboxylic acid [4-(1-cyano-cyclohexyl)-2-(4,4-dimethyl-cyclohex-1-enyl)-phenyl]-amide

HRID 2408508Notes

Reaction equation

HRID 2408508 reaction equation
[C:1]([C:3]1([C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]([C:18]3[N:19](COCC[Si](C)(C)C)[CH:20]=[C:21]([C:23]#[N:24])[N:22]=3)=[O:17])=[C:11]([C:33]3[CH2:38][CH2:37][C:36]([CH3:40])([CH3:39])[CH2:35][CH:34]=3)[CH:10]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1)#[N:2].C(O)(C(F)(F)F)=O>C(Cl)Cl.CCO>[C:1]([C:3]1([C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]([C:18]3[NH:19][CH:20]=[C:21]([C:23]#[N:24])[N:22]=3)=[O:17])=[C:11]([C:33]3[CH2:38][CH2:37][C:36]([CH3:40])([CH3:39])[CH2:35][CH:34]=3)[CH:10]=2)[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]1)#[N:2]

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 589937584-Cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid [4-(1-cyano-cyclohexyl)-2-(4,4-dimethyl-cyclohex-1-enyl)-phenyl]-amide

Product 1

HCID 1784244654-Cyano-1H-imidazole-2-carboxylic acid [4-(1-cyano-cyclohexyl)-2-(4,4-dimethyl-cyclohex-1-enyl)-phenyl]-amideYield 43%

Reagents, catalysts & solvents 2

HCID 702EthanolCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of 4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid [4-(1-cyano-cyclohexyl)-2-(4,4-dimethyl-cyclohex-1-enyl)-phenyl]-amide (66.0 mg, 0.118 mmol, as prepared in the previous step) in CH2Cl2 (6 mL) was treated with EtOH (3 drops) and TFA (0.8 mL) at RT for 2 h. Solvents were evaporated in vacuo. Purification of the residue by RP-HPLC (C18) with 20-80% CH3CN in 0.1% TFA/H2O over 25 min afforded the title compound (25.7 mg, 43%) as a white solid. 1H-NMR (CD3OD; 400 MHz): δ 8.20 (d, 1H, J=8.8 Hz), 7.93 (s, 1H), 7.37 (dd, 1H, J=8.8, 2.0 Hz), 7.26 (d, 1H, J=2.0 Hz), 5.73-5.67 (m, 1H), 2.29-2.21 (m, 2H), 2.08-1.98 (m, 4H), 1.88-1.68 (m, 6H), 1.58-1.50 (m, 2H), 1.02 (s, 6H). Mass spectrum (ESI, m/z): Calcd. for C26H29N5O, 428.2 (M+H), found 428.2.

Workup

  1. customSolvents were evaporated in vacuo
  2. customPurification of the residue by RP-HPLC (C18) with 20-80% CH3CN in 0.1% TFA/H2O over 25 min

Sources & evidence

ORD record
ord-87554093b4e8464a873ded996538c564
Source dataset
uspto-grants-2014_08
Patent number
US08815867B2

Reaction notes

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