Hydrochloric Acid → 4-((1R,2R)-2-Methyl-cyclohexylamino)-3-(2-thiophen-2-yl-acetylamino)-benzoic acid methyl ester

HRID 1750234Notes

Reaction equation

HRID 1750234 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][C:7]([OH:9])=O.C1C=NC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[CH3:29][O:30][C:31](=[O:47])[C:32]1[CH:37]=[CH:36][C:35]([NH:38][C@@H:39]2[CH2:44][CH2:43][CH2:42][CH2:41][C@H:40]2[CH3:45])=[C:34]([NH2:46])[CH:33]=1.Cl>CN(C=O)C.O.C(Cl)CCl>[CH3:29][O:30][C:31](=[O:47])[C:32]1[CH:37]=[CH:36][C:35]([NH:38][C@@H:39]2[CH2:44][CH2:43][CH2:42][CH2:41][C@H:40]2[CH3:45])=[C:34]([NH:46][C:7](=[O:9])[CH2:6][C:2]2[S:1][CH:5]=[CH:4][CH:3]=2)[CH:33]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 159702-Thiopheneacetic acidHCID 81531Diisopropylethylamine2×HCID 181649HOAtHCID 867144383-Amino-4-((1R,2R)-2-methyl-cyclohexylamino)-benzoic acid methyl ester

Product 1

HCID 867144424-((1R,2R)-2-Methyl-cyclohexylamino)-3-(2-thiophen-2-yl-acetylamino)-benzoic acid methyl esterYield 86.4%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 4.46 g of 2-thienyl-acetic acid in 80 ml of dry DMF 1.94 g of HOAT, 6.56 g of EDC and 9 ml of DIPEA were added at 0° C. After 30 min 7.48 g of 3-Amino-4-((1R,2R)-2-methyl-cyclohexylamino)-benzoic acid methyl ester were added, followed by the addition of 9 ml of DIPEA and the reaction was stirred at rt for 16 h. The reaction was then poured into water, brought to pH3 by the addition of 2 M aqueous hydrochloric acid and extracted with ethyl acetate three times. The combined organic phases were washed with saturated aqueous sodium bicarbonate solution and brine, dried over magnesium sulphate and concentrated to obtain 9.52 g (86%) of 4-((1R,2R)-2-Methyl-cyclohexylamino)-3-(2-thiophen-2-yl-acetylamino)-benzoic acid methyl ester, which was used without further purification.

Workup

  1. extractionextracted with ethyl acetate three times
  2. washThe combined organic phases were washed with saturated aqueous sodium bicarbonate solution and brine
  3. dry with materialdried over magnesium sulphate
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-13b76b6493644d9991544478bd5b9957
Source dataset
uspto-grants-2015_10
Patent number
US09156796B2

Reaction notes

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