Potassium bis(trimethylsilyl)amide → 5-(3,3-Dimethyl-but-1-ynyl)-3-{(4-methyl-cyclohexanecarbonyl)-[4-(pyridin-2-yloxy)-phenyl]-amino}-thiophene-2-carboxylic acid methyl ester

HRID 1046412Notes

Reaction equation

HRID 1046412 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:24]#[C:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[CH:8][C:9]=1[NH:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=2)=[CH:13][CH:12]=1)=[O:4].C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH3:40][C@H:41]1[CH2:46][CH2:45][C@H:44]([C:47](Cl)=[O:48])[CH2:43][CH2:42]1>C1COCC1>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:24]#[C:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[CH:8][C:9]=1[N:10]([C:47]([CH:44]1[CH2:45][CH2:46][CH:41]([CH3:40])[CH2:42][CH2:43]1)=[O:48])[C:11]1[CH:12]=[CH:13][C:14]([O:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=2)=[CH:15][CH:16]=1)=[O:4]

Participants

5

Reactant 3

HCID 3251421Potassium bis(trimethylsilyl)amideHCID 581140985-(3,3-Dimethyl-but-1-ynyl)-3-[4-(pyridin-2-yloxy)-phenylamino]-thiophene-2-carboxylic acid methyl esterHCID 178461265HCID 178461265, compound

Product 1

HCID 581138635-(3,3-Dimethyl-but-1-ynyl)-3-{(4-methyl-cyclohexanecarbonyl)-[4-(pyridin-2-yloxy)-phenyl]-amino}-thiophene-2-carboxylic acid methyl esterYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a cooled (0° C.) THF (5 mL) solution of 5-(3,3-Dimethyl-but-1-ynyl)-3-[4-(pyridin-2-yloxy)-phenylamino]-thiophene-2-carboxylic acid methyl ester (0.225 g, 0.55 mmol) was first added KHMDS (0.66 mmol, 0.5 M in toluene), followed by neat trans-4-methyl-cyclohexanecarbonyl chloride (0.132 g, 0.825 mmol). The reaction was warmed slowly to room temperature and quenched with saturated ammonium chloride solution. The reaction mixture was diluted with EtOAc, washed with water, brine, dried over sodium sulfate, filtrated and concentrated. The crude material was purified by silica gel column chromatography to give 5-(3,3-dimethyl-but-1-ynyl)-3-{(4-methyl-cyclohexanecarbonyl)-[4-(pyridin-2-yloxy)-phenyl]-amino}-thiophene-2-carboxylic acid methyl ester in 60% yield.

Workup

  1. customquenched with saturated ammonium chloride solution
  2. additionThe reaction mixture was diluted with EtOAc
  3. washwashed with water, brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltrated
  6. concentrationconcentrated
  7. customThe crude material was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-5adcad450e244050b40cefa486cf5f0d
Source dataset
uspto-grants-2013_10
Patent number
US08569302B2

Reaction notes

Loading…