Triethylamine → 5-[(1H-indol-4-ylmethyl)-carbamoyl]-3-methyl-thiophene-2-carboxylic acid methyl ester

HRID 1952566Notes

Reaction equation

HRID 1952566 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:11]([OH:13])=O)=[CH:8][C:9]=1[CH3:10])=[O:4].C([N:16]([CH2:19][CH3:20])[CH2:17][CH3:18])C.C1[CH:22]=[CH:23][C:24]2N(O)N=[N:27][C:25]=2C=1.[CH3:31]N(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:11](=[O:13])[NH:27][CH2:25][C:24]2[CH:23]=[CH:22][CH:18]=[C:17]3[C:31]=2[CH:20]=[CH:19][NH:16]3)=[CH:8][C:9]=1[CH3:10])=[O:4]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 682266195-(Methoxycarbonyl)-4-methylthiophene-2-carboxylic acid

Product 1

HCID 682268105-[(1H-indol-4-ylmethyl)-carbamoyl]-3-methyl-thiophene-2-carboxylic acid methyl esterYield 36.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-methyl-thiophene-2,5-dicarboxylic acid 2-methyl ester (200 mg,) mmol) and C-(1H-indol-4-yl)-methylam (219 mg, 1.5 mmol) in DMF (5 ml) was added at rt triethylamine (0.42 ml, 3 mmol), HOBT (162 mg, 1.2 mmol) and HBTU (455 mg, 1.2 mmol). The mixture was stirred at rt for 30 min, then quenched with 1NHCl and extracted with EtOAc. The layers were separated. The organic layer was successively washed with water and brine, then dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by flash chromatography with 20-60% EtOAc in hexane to afford the desired product (119 mg, 36% yield).

Workup

  1. customquenched with 1NHCl and
  2. extractionextracted with EtOAc
  3. customThe layers were separated
  4. washThe organic layer was successively washed with water and brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by flash chromatography with 20-60% EtOAc in hexane

Sources & evidence

ORD record
ord-24cfb40179094966bb0bf75ef433d91d
Source dataset
uspto-grants-2013_03
Patent number
US08404859B2

Reaction notes

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