Pyridine → 3-[(1-Acetyl-piperidin-4-yl)-(4-methyl-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester

HRID 73191Notes

Reaction equation

HRID 73191 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[CH:8][C:9]=1[N:10]([C:17]([CH:19]1[CH2:24][CH2:23][CH:22]([CH3:25])[CH2:21][CH2:20]1)=[O:18])[CH:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1)=[O:4].N1C=CC=CC=1.[C:38](OC(=O)C)(=[O:40])[CH3:39]>ClCCl.CN(C1C=CN=CC=1)C>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)=[CH:8][C:9]=1[N:10]([CH:11]1[CH2:16][CH2:15][N:14]([C:38](=[O:40])[CH3:39])[CH2:13][CH2:12]1)[C:17]([CH:19]1[CH2:20][CH2:21][CH:22]([CH3:25])[CH2:23][CH2:24]1)=[O:18])=[O:4]

Participants

6

Reactant 3

HCID 1049PyridineHCID 7918Acetic AnhydrideHCID 59752320HCID 59752320, compound

Product 1

HCID 597522933-[(1-Acetyl-piperidin-4-yl)-(4-methyl-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl esterYield 78.5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To 3-[(4-Methyl-cyclohexanecarbonyl)-piperidin-4-yl-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester (58 mg, 0.132 mmol) in dichloromethane (1.3 ml) was added pyridine (64 ul, 0.789 mmol), followed by acetic anhydride (50 ul, 0.526 mmol) and a catalytic amount of DMAP. The resulting solution was stirred for 18 hours at room temperature and then quenched with a saturated solution of NaHCO3 (5 ml). The aqueous phase was separated and washed with ethyl acetate (2×5 ml). The combined organic layers were dried (Na2SO4), filtered and concentrated. The residue was then purified by preparative chromatography (100/90/16/1 CH2Cl2/CHCl3/MeOH/Et3N) to obtain 50 mg (78%) of 3-[(1-Acetyl-piperidin-4-yl)-(4-methyl-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester.

Workup

  1. customquenched with a saturated solution of NaHCO3 (5 ml)
  2. customThe aqueous phase was separated
  3. washwashed with ethyl acetate (2×5 ml)
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was then purified by preparative chromatography (100/90/16/1 CH2Cl2/CHCl3/MeOH/Et3N)

Sources & evidence

ORD record
ord-e4dc175fde014fa69697c949924d2bc9
Source dataset
uspto-grants-2014_09
Patent number
US08829030B2

Reaction notes

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