Methanol → HCID 178499270, compound

HRID 1694457Notes

Reaction equation

HRID 1694457 reaction equation
[CH3:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([C:8](Cl)=[O:9])[CH2:4][CH2:3]1.[CH3:11][O:12][C:13]([C:15]1[S:16][C:17]([C:31]2[CH2:36][CH2:35][CH2:34][CH2:33][CH:32]=2)=[CH:18][C:19]=1[NH:20][CH:21]1[CH2:29][CH:28]2[N:24]([C:25](=[O:30])[CH2:26][CH2:27]2)[CH2:23][CH2:22]1)=[O:14].N1C=CC=CC=1.CO>C1(C)C=CC=CC=1.ClCCl>[CH3:11][O:12][C:13]([C:15]1[S:16][C:17]([C:31]2[CH2:36][CH2:35][CH2:34][CH2:33][CH:32]=2)=[CH:18][C:19]=1[N:20]([C:8]([C@H:5]1[CH2:6][CH2:7][C@H:2]([CH3:1])[CH2:3][CH2:4]1)=[O:9])[CH:21]1[CH2:29][CH:28]2[N:24]([C:25](=[O:30])[CH2:26][CH2:27]2)[CH2:23][CH2:22]1)=[O:14]

Participants

7

Reactant 4

HCID 887MethanolHCID 1049Pyridine2×HCID 577954965-Cyclohex-1-enyl-3-[(3-oxo-octahydro-indolizin-7-yl)-amino]-thiophene-2-carboxylic acid methyl esterHCID 178461265HCID 178461265, compound

Product 1

HCID 178499270HCID 178499270, compoundYield 64%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

trans-4-Methylcyclohexyl carboxylic acid chloride was added to a solution of 5-cyclohex-1-enyl-3-[(3-oxo-octahydro-indolizin-7-yl)-amino]-thiophene-2-carboxylic acid methyl ester (698 mg, 1.86 mmol) and pyridine (166 μL, 2.05 mmol) in dry toluene (8 mL). The mixture was refluxed for 16 h, then it was brought to room temperature, additional amount of pyridine (0.2 mL) and MeOH (1 mL) were added. The mixture was diluted with dichloromethane, washed with brine; organic phase was dried over Na2SO4, concentrated and purified by column chromatography on silica gel using gradient 0-100% EtOAc in hexane to afford 592 mg (64%) of 5-cyclohex-1-enyl-3-[(trans-4-methyl-cyclohexanecarbonyl)-(3-oxo-octahydro-indolizin-7-yl)-amino]-thiophene-2-carboxylic acid methyl ester.

Workup

  1. temperatureThe mixture was refluxed for 16 h
  2. customwas brought to room temperature
  3. washwashed with brine
  4. dry with materialorganic phase was dried over Na2SO4
  5. concentrationconcentrated
  6. custompurified by column chromatography on silica gel using gradient 0-100% EtOAc in hexane

Sources & evidence

ORD record
ord-0e2c3b503ca14027a60438926954927f
Source dataset
uspto-grants-2012_04
Patent number
US08158675B2

Reaction notes

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