Triethylamine → N-(4-(3-(2-chlorobenzoyl)-5-ethylthiophen-2-yl)-5-methyl[1,2,4]triazol-3-yl-methyl)-3-methyl-1H-indole-2-carboxamide

HRID 963087Notes

Reaction equation

HRID 963087 reaction equation
[CH3:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[NH:4][C:3]=1[C:11]([OH:13])=O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.[NH2:36][CH2:37][C:38]1[N:42]([C:43]2[S:44][C:45]([CH2:57][CH3:58])=[CH:46][C:47]=2[C:48](=[O:56])[C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][C:50]=2[Cl:55])[C:41]([CH3:59])=[N:40][N:39]=1.C(N(CC)CC)C.CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O>[Cl:55][C:50]1[CH:51]=[CH:52][CH:53]=[CH:54][C:49]=1[C:48]([C:47]1[CH:46]=[C:45]([CH2:57][CH3:58])[S:44][C:43]=1[N:42]1[C:41]([CH3:59])=[N:40][N:39]=[C:38]1[CH2:37][NH:36][C:11]([C:3]1[NH:4][C:5]2[C:10]([C:2]=1[CH3:1])=[CH:9][CH:8]=[CH:7][CH:6]=2)=[O:13])=[O:56]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 27526383-Methyl-1H-indole-2-carboxylic acidHCID 190850953-Aminomethyl-4-(3-(2-chlorobenzoyl)-5-ethylthiophen-2-yl)-5-methyl[1,2,4]triazole ditosylate

Product 1

HCID 19085326N-(4-(3-(2-chlorobenzoyl)-5-ethylthiophen-2-yl)-5-methyl[1,2,4]triazol-3-yl-methyl)-3-methyl-1H-indole-2-carboxamideYield 14.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

3-Methylindole-2-carboxylic acid (0.5 g) and 3-aminomethyl-4-(3-(2-chlorobenzoyl)-5-ethylthiophen-2-yl)-5-methyl[1,2,4]triazole di-p-toluenesulfonate (2.1 g) was dissolved in DMF (42 ml). Triethylamine (1.6 ml) and Bop reagent (1.32 g) were added under ice-cooling, and the mixture was stirred for 6 hours. Water was added, and the mixture was extracted with ethyl acetate. The extract was washed with an aqueous citric acid solution, saturated brine, a saturated aqueous sodium hydrogencarbonate solution and saturated brine, and dried over magnesium sulfate. The solvent was evaporated, and the residue was purified by silica gel column chromatography using a mixed solvent of ethyl acetate and methanol as an eluent and recrystallized from a mixed solvent of ethyl acetate and hexane to give 0.22 g of N-(4-(3-(2-chlorobenzoyl)-5-ethylthiophen-2-yl)-5-methyl[1,2,4]triazol-3-yl-methyl)-3-methyl-1H-indole-2-carboxamide.

Workup

  1. temperaturecooling
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe extract was washed with an aqueous citric acid solution, saturated brine
  4. dry with materiala saturated aqueous sodium hydrogencarbonate solution and saturated brine, and dried over magnesium sulfate
  5. customThe solvent was evaporated
  6. customthe residue was purified by silica gel column chromatography
  7. customrecrystallized from a mixed solvent of ethyl acetate and hexane

Sources & evidence

ORD record
ord-3679349442bb4cb4bb40fbd77ef52dc8
Source dataset
uspto-grants-1998_06
Patent number
US05760032

Reaction notes

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