Pyridine → HCID 178499268, compound

HRID 1190058Notes

Reaction equation

HRID 1190058 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:22]2[CH2:27][CH2:26][CH2:25][CH2:24][CH:23]=2)=[CH:8][C:9]=1[NH:10][CH:11]1[CH2:16][CH2:15][CH:14]([N:17]2[CH:21]=[N:20][CH:19]=[N:18]2)[CH2:13][CH2:12]1)=[O:4].[CH3:28][C@H:29]1[CH2:34][CH2:33][C@H:32]([C:35](Cl)=[O:36])[CH2:31][CH2:30]1.C1(C)C=CC=CC=1.N1C=CC=CC=1>CCOC(C)=O>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:22]2[CH2:27][CH2:26][CH2:25][CH2:24][CH:23]=2)=[CH:8][C:9]=1[N:10]([C:35]([C@H:32]1[CH2:33][CH2:34][C@H:29]([CH3:28])[CH2:30][CH2:31]1)=[O:36])[CH:11]1[CH2:16][CH2:15][CH:14]([N:17]2[CH:21]=[N:20][CH:19]=[N:18]2)[CH2:13][CH2:12]1)=[O:4]

Participants

6

Reactant 4

HCID 1049PyridineHCID 1140TolueneHCID 577954275-Cyclohex-1-enyl-3-(4-[1,2,4]triazol-1-yl-cyclohexylamino)-thiophene-2-carboxylic acid methyl esterHCID 178461265HCID 178461265, compound

Product 1

HCID 178499268HCID 178499268, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

5-cyclohex-1-enyl-3-(4-[1,2,4]triazol-1-yl-cyclohexylamino)-thiophene-2-carboxylic acid methyl ester (555 mg, 1.436 mmol) was treated with a 1M solution of trans-4-methylcyclohexanecarbonyl chloride in toluene (2.87 mL, 2.87 mmol). Pyridine (128 μl, 1.58 mmol) was added and the mixture was stirred at reflux overnight under nitrogen. It was cooled to room temperature and dilute with EtOAc. The resulting mixture was washed twice with a saturated aqueous sodium bicarbonate and once with brine, dried over Na2SO4 and concentrated. The crude was purified by silica gel column chromatography using a gradient from 50% EtOAc:hexanes to 100% EtOAc as eluent to afford 5-cyclohex-1-enyl-3-[(trans-4-methyl-cyclohexanecarbonyl)-(4-[1,2,4]triazol-1-yl-cyclohexyl)-amino]-thiophene-2-carboxylic acid methyl ester (494 mg, 67%) as a yellow mixture of cis and trans isomers.

Workup

  1. temperatureat reflux overnight under nitrogen
  2. washThe resulting mixture was washed twice with a saturated aqueous sodium bicarbonate and once with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe crude was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-55dddece41654a22893f3bf9983909a5
Source dataset
uspto-grants-2014_03
Patent number
US08674118B2

Reaction notes

Loading…