Methanol → HCID 178499336, compound

HRID 2388291Notes

Reaction equation

HRID 2388291 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.N1C=CC=CC=1.[CH3:17][O:18][C:19]([C:21]1[S:22][C:23]([C:40]#[C:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[CH:24][C:25]=1[NH:26][CH:27]1[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH2:28]1)=[O:20].CO>C1(C)C=CC=CC=1.C(Cl)Cl>[CH3:17][O:18][C:19]([C:21]1[S:22][C:23]([C:40]#[C:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[CH:24][C:25]=1[N:26]([C:8]([C@H:5]1[CH2:6][CH2:7][C@H:2]([CH3:1])[CH2:3][CH2:4]1)=[O:9])[CH:27]1[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:37])([CH3:38])[CH3:39])=[O:34])[CH2:29][CH2:28]1)=[O:20]

Participants

7

Reactant 4

HCID 887MethanolHCID 1049Pyridine2×HCID 666035305-(3,3-dimethyl-but-1-ynyl)-3-(N-tert-butoxycarbonyl-piperidin-4-yl)amino-thiophene-2-carboxylic acid methyl esterHCID 178461265HCID 178461265, compound

Product 1

HCID 178499336HCID 178499336, compoundYield 78%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

trans-4-Methylcyclohexyl carboxylic acid chloride (23.88 mmol) and pyridine (2.89 mL, 35.82 mmol) are added to a solution of 5-(3,3-dimethyl-but-1-ynyl)-3-(N-tert-butoxycarbonyl-piperidin-4-yl)amino-thiophene-2-carboxylic acid methyl ester from step III (5.142 g) in dry toluene (50 mL). The mixture is refluxed for 24 h, then it is brought to room temperature, and additional amount of pyridine (1.0 mL) and MeOH (5 mL) are added. Then the mixture is diluted with CH2Cl2, washed with brine, organic fraction is separated, dried over Na2SO4, and concentrated to give 5.198 g of crude 5-(3,3-dimethyl-but-1-ynyl)-3-[(trans-4-methyl-cyclohexanecarbonyl)-(N-tert-butoxycarbonyl-piperidin-4-yl)amino]-thiophene-2-carboxylic acid methyl ester containing variable amounts of 5-(3,3-dimethyl-but-1-ynyl)-3-[(trans-4-methyl-cyclohexanecarbonyl)-(piperidin-4-yl)-amino]-thiophene-2-carboxylic acid methyl ester.

Workup

  1. temperatureThe mixture is refluxed for 24 h
  2. customis brought to room temperature
  3. washwashed with brine, organic fraction
  4. customis separated
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-6cbbd6fb4e0d4189a79482ae6b036ebb
Source dataset
uspto-grants-2012_09
Patent number
US08269014B2

Reaction notes

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