Dimethylformamide → 3-[[1-(4-Methoxy-benzyl)-2-oxo-piperidin-4-yl]-(4-methyl-cyclohexanecarbonyl)-amino]-5-(1-methyl-hexa-1,3,5-trienyl)-thiophene-2-carboxylic acid methyl ester

HRID 749389Notes

Reaction equation

HRID 749389 reaction equation
[CH3:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([C:8]([OH:10])=O)[CH2:4][CH2:3]1.C(Cl)(=O)C(Cl)=O.CN(C)C=O.[CH3:22][O:23][C:24]([C:26]1[S:27][C:28]([C:48]([CH3:54])=[CH:49][CH:50]=[CH:51][CH:52]=[CH2:53])=[CH:29][C:30]=1[NH:31][CH:32]1[CH2:37][CH2:36][N:35]([CH2:38][C:39]2[CH:44]=[CH:43][C:42]([O:45][CH3:46])=[CH:41][CH:40]=2)[C:34](=[O:47])[CH2:33]1)=[O:25]>ClCCCl>[CH3:22][O:23][C:24]([C:26]1[S:27][C:28]([C:48]([CH3:54])=[CH:49][CH:50]=[CH:51][CH:52]=[CH2:53])=[CH:29][C:30]=1[N:31]([CH:32]1[CH2:37][CH2:36][N:35]([CH2:38][C:39]2[CH:40]=[CH:41][C:42]([O:45][CH3:46])=[CH:43][CH:44]=2)[C:34](=[O:47])[CH2:33]1)[C:8]([CH:5]1[CH2:4][CH2:3][CH:2]([CH3:1])[CH2:7][CH2:6]1)=[O:10])=[O:25]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 865958573-[1-(4-Methoxy-benzyl)-2-oxo-piperidin-4-ylamino]-5-(1-methyl-hexa-1,3,5-trienyl)-thiophene-2-carboxylic acid methyl esterHCID 178461286HCID 178461286, compound

Product 1

HCID 865958563-[[1-(4-Methoxy-benzyl)-2-oxo-piperidin-4-yl]-(4-methyl-cyclohexanecarbonyl)-amino]-5-(1-methyl-hexa-1,3,5-trienyl)-thiophene-2-carboxylic acid methyl esterYield 11%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent2×

Procedure

A solution of trans 4-methylcyclohexane carboxylic acid (56 mg, 0.399 mmol, 1.2 eq)in 1,2-dichloroethane (1 ml) at 0°, under N2, was treated with oxalyl chloride (2.0M solution in CH2C12)(231 μl, 0.46 mmol, 1.4 eq), followed by dimethylformamide (8 μl, 7 mg, 0.1 mmol, 30 mol %). After 1 h the reaction was treated with a solution of 3-[1-(4-Methoxy-benzyl)-2-oxo-piperidin-4-ylamino]-5-(1-methyl-hexa-1,3,5-trienyl)-thiophene-2-carboxylic acid methyl ester (150 mg, 0.33 mmol) in DCE (2 ml). The reaction was then placed in abth at 90° and left at reflux overnight for 21 h. The reaction was stripped-off solvent and the residue (212 mg) was purified by bond elute chromatography using (Hexane:CH2Cl2:EtOAc=1:1:1) as eluent to give 3-[[1-(4-Methoxy-benzyl)-2-oxo-piperidin-4-yl]-(4-methyl-cyclohexanecarbonyl)-amino]-5-(1-methyl-hexa-1,3,5-trienyl)-thiophene-2-carboxylic acid methyl ester (21 mg, 11%) as a yellow foam; (300 MHz, CDCl3)0.55-0.73 (m, 1H), 0.77 (d, J=5.4 Hz, 3H), 1.26-1.30 (m, 12H), 1.94-2.12 (m, 1H), 2.14-2.19 (m, 1H), 2.40 (dd, J=9.0 Hz, J=12.0 Hz, 1H), 2.64-2.70 and 2.80 and 2.84 (m, 1H), 3.10-3.15 (m, 3H), 3.79-3.82 (m, 1H), 3.78 (s, 3H), 3.83 and 3.87 (s, 3H), 4.32 (t, J=12.0 Hz, 1H), 4.62 (dd, J=5.7 Hz, J=10.8 Hz, 1H), 4.50-5.0 (m, 1H), 6.79-6.83 (m, 2H), 6.99-7.14 (m, 2H), 7.26-7.48 (m, 3H), 7.61-7.65 (m, 2H).

Workup

  1. customwas then placed in abth at 90°
  2. waitleft
  3. temperatureat reflux overnight for 21 h
  4. customthe residue (212 mg) was purified by bond
  5. washelute chromatography

Sources & evidence

ORD record
ord-91167b0682b24f2fb717e498fa8f3a48
Source dataset
uspto-grants-2008_07
Patent number
US07402608B2

Reaction notes

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