Hydrochloric Acid → 4-(2-Methyl-cyclopentylamino)-3-(2-thiophen-2-yl-acetylamino)-benzoic acid methyl ester

HRID 1750246Notes

Reaction equation

HRID 1750246 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:46])[C:32]1[CH:37]=[CH:36][C:35]([NH:38][CH:39]2[CH2:43][CH2:42][CH2:41][CH:40]2[CH3:44])=[C:34]([NH2:45])[CH:33]=1.Cl>CN(CC1C=C(CN(C)C)C(O)=C(CN(C)C)C=1)C.C(OCC)(=O)C.O.C(Cl)CCl>[CH3:29][O:30][C:31](=[O:46])[C:32]1[CH:37]=[CH:36][C:35]([NH:38][CH:39]2[CH2:43][CH2:42][CH2:41][CH:40]2[CH3:44])=[C:34]([NH:45][C:7](=[O:9])[CH2:6][C:2]2[S:1][CH:5]=[CH:4][CH:3]=2)[CH:33]=1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 159702-Thiopheneacetic acidHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 632795193-Amino-4-(2-methyl-cyclopentylamino)-benzoic acid methyl ester

Product 1

HCID 867144534-(2-Methyl-cyclopentylamino)-3-(2-thiophen-2-yl-acetylamino)-benzoic acid methyl esterYield 100.3%

Reagents, catalysts & solvents 4

HCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 70262,4,6-Tris((dimethylamino)methyl)phenolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3.44 g of thiophen-2-yl-acetic acid in 40 ml of dry DMF 3.62 g of HOAT, 6.48 g of EDC and 12 ml of DIPEA were added at 0° C. After 30 min 6.00 g of 3-Amino-4-(2-methyl-cyclopentylamino)-benzoic acid methyl ester were added, and the reaction was stirred at rt for 16 h. The reaction was then poured into water and the pH was adjusted to 3 by the addition of 2 m aqueous hydrochloric acid. Ethyl acetate was added and the layers were separated. The aqueous layer was 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 9.03 g (100%) of 4-(2-Methyl-cyclopentylamino)-3-(2-thiophen-2-yl-acetylamino)-benzoic acid methyl ester, which was used without further purification.

Workup

  1. customthe layers were separated
  2. extractionThe aqueous layer was extracted with ethyl acetate three times
  3. washThe combined organic phases were washed with saturated aqueous sodium bicarbonate solution and brine
  4. dry with materialdried over magnesium sulphate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-1b185dc523244d1fb0e5e008317041e5
Source dataset
uspto-grants-2015_10
Patent number
US09156796B2

Reaction notes

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