1,2-Dichloroethane → 5-[(2-oxo-2,3-dihydro-1H-indol-4-ylmethyl)-carbamoyl]-3-trifluoromethyl-thiophene-2-carboxylic acid methyl ester

HRID 1952601Notes

Reaction equation

HRID 1952601 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:14]([OH:16])=O)=[CH:8][C:9]=1[C:10]([F:13])([F:12])[F:11])=[O:4].C(N(CC)CC)C.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.Cl.[NH2:39][CH2:40][C:41]1[CH:49]=[CH:48][CH:47]=[C:46]2[C:42]=1[CH2:43][C:44](=[O:50])[NH:45]2>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:14](=[O:16])[NH:39][CH2:40][C:41]2[CH:49]=[CH:48][CH:47]=[C:46]3[C:42]=2[CH2:43][C:44](=[O:50])[NH:45]3)=[CH:8][C:9]=1[C:10]([F:11])([F:12])[F:13])=[O:4]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 226614464-(Aminomethyl)indolin-2-one hydrochlorideHCID 682266025-(Methoxycarbonyl)-4-(trifluoromethyl)thiophene-2-carboxylic acid

Product 1

HCID 682267015-[(2-oxo-2,3-dihydro-1H-indol-4-ylmethyl)-carbamoyl]-3-trifluoromethyl-thiophene-2-carboxylic acid methyl esterYield 29.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-Trifluoromethyl-thiophene-2,5-dicarboxylic acid 2-methyl ester (590 mg, 2.32 mmol) in anhydrous DMF (10 mL) was added triethylamine (1.62 mL, 11.6 mmol), EDC (530 mg, 2.78 mmol), HOBT (380 mg, 2.78 mmol), and 4-Aminomethyl-1,3-dihydro-indol-2-one hydrochloride (550 mg, 2.78 mmol). The mixture was stirred at room temperature 15 h, then quenched by pouring into EtOAc. The organic layer was washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by flash chromatography with 0-90% EtOAc in hexane to afford the desired product (0.27 g, 29% yield).

Workup

  1. customquenched
  2. additionby pouring into EtOAc
  3. washThe organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by flash chromatography with 0-90% EtOAc in hexane

Sources & evidence

ORD record
ord-044c5f7a258545b0aa938e8af1105b55
Source dataset
uspto-grants-2013_03
Patent number
US08404859B2

Reaction notes

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