Methanol → HCID 178499252, compound

HRID 1694488

Reaction equation

HRID 1694488 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([Br:19])=[CH:8][C:9]=1[NH:10][CH:11]1[CH2:16][O:15][C:14]([CH3:18])([CH3:17])[O:13][CH2:12]1)=[O:4].N1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.[CH3:26]O.C([O:31][CH2:32][CH3:33])(=O)C>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([Br:19])=[CH:8][C:9]=1[N:10]([CH:11]1[CH2:16][O:15][C:14]([CH3:17])([CH3:18])[O:13][CH2:12]1)[C:32]([C@H:33]1[CH2:25][CH2:24][C@H:23]([CH3:26])[CH2:22][CH2:21]1)=[O:31])=[O:4]

Participants

6

Reactant 4

HCID 887MethanolHCID 1049Pyridine3×HCID 8857Ethyl AcetateHCID 577954295-Bromo-3-(2,2-dimethyl-[1,3]dioxan-5-ylamino)-thiophene-2-carboxylic acid methyl ester

Product 1

HCID 178499252HCID 178499252, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent3×

Conditions

Temperature
5 °C

Procedure

To a mixture of 5-bromo-3-(2,2-dimethyl-[1,3]dioxan-5-ylamino)-thiophene-2-carboxylic acid methyl ester (200 mg, 0.57 mmol) in toluene (1 mL) and pyridine (100 μl, 1.23 mmol), acid chloride in toluene prepared above (1.1 mL, 1.05 mmol) was added. The reaction mixture was refluxed for 16 h. TLC showed the presence of starting material. Pyridine (50 μl, 0.62 mmol) and acid chloride in totuene (0.5 mL, 0.47 mmol) were added and the refluxing was continued for 24 h. The mixture was cooled to 5° C. Toluene (2 mL) and pyridine (0.2 mL) were added. After stirring for 5 min MeOH (0.5 mL) was added and the mixture was stirred for 10 min. It was diluted with ethyl acetate, washed with saturated NaHCO3 and brine, dried and evaporated. The crude reaction mixture was chromatographed over silica gel (hexane-ethyl acetate mixtures as eluents) yielding 5-bromo-3-[(2,2-dimethyl-[1,3]dioxan-5-yl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester (35 mg) contaminated with a small impurity. This material was used for the next step.

Workup

  1. customprepared above (1.1 mL, 1.05 mmol)
  2. additionwas added
  3. temperatureThe reaction mixture was refluxed for 16 h
  4. additionwas added
  5. washwashed with saturated NaHCO3 and brine
  6. customdried
  7. customevaporated
  8. customThe crude reaction mixture
  9. customwas chromatographed over silica gel (hexane-ethyl acetate mixtures as eluents)

Sources & evidence

ORD record
ord-fbc8673a5a4c4255b206507c991cf185
Source dataset
uspto-grants-2012_04
Patent number
US08158675B2

Linked notes

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