Hydrochloric Acid → 1-((1R,2R)-2-Methyl-cyclohexyl)-2-thiazol-5-ylmethyl-1H-benzoimidazole-5-carboxylic acid methyl ester

HRID 1750232Notes

Reaction equation

HRID 1750232 reaction equation
[CH3:1][O:2][C:3](=[O:27])[C:4]1[CH:9]=[CH:8][C:7]([NH:10][C@@H:11]2[CH2:16][CH2:15][CH2:14][CH2:13][C@H:12]2[CH3:17])=[C:6]([NH:18][C:19](=O)[CH2:20][C:21]2[S:25][CH:24]=[N:23][CH:22]=2)[CH:5]=1.Cl>O1CCOCC1>[CH3:1][O:2][C:3]([C:4]1[CH:9]=[CH:8][C:7]2[N:10]([C@@H:11]3[CH2:16][CH2:15][CH2:14][CH2:13][C@H:12]3[CH3:17])[C:19]([CH2:20][C:21]3[S:25][CH:24]=[N:23][CH:22]=3)=[N:18][C:6]=2[CH:5]=1)=[O:27]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 867144394-((1R,2R)-2-Methyl-cyclohexylamino)-3-(2-thiazol-5-yl-acetylamino)-benzoic acid methyl ester

Product 1

HCID 867144401-((1R,2R)-2-Methyl-cyclohexyl)-2-thiazol-5-ylmethyl-1H-benzoimidazole-5-carboxylic acid methyl esterYield 31%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To 1.26 g 4-((1R,2R)-2-Methyl-cyclohexylamino)-3-(2-thiazol-5-yl-acetylamino)-benzoic acid methyl ester in 10 ml dioxane were added 12 ml of 4M hydrochloric acid in dioxane and the mixture was heated to reflux for 2 h. The reaction was concentrated and the residue was taken up in ethyl acetate and washed with saturated aqueous sodium bicarbonate solution and brine. The organic layers were dried over sodium sulphate and concentrated. The resulting residue was purified by HPLC to yield 0.37 g (31%) of 1-((1R,2R)-2-Methyl-cyclohexyl)-2-thiazol-5-ylmethyl-1H-benzoimidazole-5-carboxylic acid methyl ester.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 2 h
  3. concentrationThe reaction was concentrated
  4. washwashed with saturated aqueous sodium bicarbonate solution and brine
  5. dry with materialThe organic layers were dried over sodium sulphate
  6. concentrationconcentrated
  7. customThe resulting residue was purified by HPLC

Sources & evidence

ORD record
ord-2f1aa88405e447018fd8d3e33571c640
Source dataset
uspto-grants-2015_10
Patent number
US09156796B2

Reaction notes

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