2-Thiopheneacetic acid → 4-(1-Ethyl-propylamino)-3-(2-thiophen-2-yl-acetylamino)-benzoic acid methyl ester

HRID 1750189Notes

Reaction equation

HRID 1750189 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][C:7]([OH:9])=O.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[CH3:29][O:30][C:31](=[O:45])[C:32]1[CH:37]=[CH:36][C:35]([NH:38][CH:39]([CH2:42][CH3:43])[CH2:40][CH3:41])=[C:34]([NH2:44])[CH:33]=1>CN(C=O)C.O.C(Cl)CCl>[CH3:29][O:30][C:31](=[O:45])[C:32]1[CH:37]=[CH:36][C:35]([NH:38][CH:39]([CH2:40][CH3:41])[CH2:42][CH3:43])=[C:34]([NH:44][C:7](=[O:9])[CH2:6][C:2]2[S:1][CH:5]=[CH:4][CH:3]=2)[CH:33]=1

Participants

8

Reactant 4

HCID 159702-Thiopheneacetic acidHCID 757711-HydroxybenzotriazoleHCID 81531Diisopropylethylamine2×HCID 61311526Methyl 3-amino-4-(pentan-3-ylamino)benzoate

Product 1

HCID 867144044-(1-Ethyl-propylamino)-3-(2-thiophen-2-yl-acetylamino)-benzoic acid methyl esterYield 77.2%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 1.56 g of thiophen-2-yl-acetic acid in 25 ml of dry DMF 1.49 g of HOBT, 2.11 g of EDC and 2.6 ml of DIPEA were added at 0° C. After 30 min 2.36 g of 3-amino-4-(1-ethyl-propylamino)-benzoic acid methyl ester and 2.6 ml of DIPEA were added and the reaction was stirred at rt for 16 h. The reaction was then poured into water 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. The crude product was purified by crystallization from diethylether to yield 2.78 g (77%) of 4-(1-ethyl-propylamino)-3-(2-thiophen-2-yl-acetylamino)-benzoic acid methyl ester.

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
  5. customThe crude product was purified by crystallization from diethylether

Sources & evidence

ORD record
ord-9d62fa8528664bf799443549f7c934af
Source dataset
uspto-grants-2015_10
Patent number
US09156796B2

Reaction notes

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