5-Fluoroindole-2-carboxylic acid → N-(4-(3-(2-chlorobenzoyl)-5-ethylthiophen-2-yl)-5-methyl[1,2,4]triazol-3-ylmethyl)-5-fluoroindole-2-carboxamide

HRID 963061Notes

Reaction equation

HRID 963061 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([OH:13])=O)=[CH:5]2.S(C1C=CC(C)=CC=1)(O)(=O)=O.S(C1C=CC(C)=CC=1)(O)(=O)=O.[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.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C)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:6]1[NH:7][C:8]2[C:4]([CH:5]=1)=[CH:3][C:2]([F:1])=[CH:10][CH:9]=2)=[O:13])=[O:56]

Participants

6

Reactant 4

HCID 18205-Fluoroindole-2-carboxylic acidHCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 190850953-Aminomethyl-4-(3-(2-chlorobenzoyl)-5-ethylthiophen-2-yl)-5-methyl[1,2,4]triazole ditosylate

Product 1

HCID 22439198N-(4-(3-(2-chlorobenzoyl)-5-ethylthiophen-2-yl)-5-methyl[1,2,4]triazol-3-ylmethyl)-5-fluoroindole-2-carboxamideYield 15.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-Fluoroindole-2-carboxylic acid (0.50 g) and 3-aminomethyl-4-(3-(2-chlorobenzoyl)-5-ethylthiophen-2-yl)-5-methyl[1,2,4]triazole ditosylate (2.07 g) were dissolved in dimethylformamide (40 ml). Triethylamine (1.6 ml) and 1-benzotriazolyloxytris(dimethylamino)phosphonium hexafluorophosphate (Bop reagent, 1.29 g) were added under ice-cooling, and the mixture was stirred for 4 hours. The reaction mixture was partitioned between water and ethyl acetate. The organic layer was washed with an aqueous citric acid solution, a saturated aqueous sodium hydrogencarbonate solution and saturated brine, and dried over magnesium sulfate. The solvent was evaporated, and the obtained residue was crystallized from ethyl acetate to give 0.23 g of N-(4-(3-(2-chlorobenzoyl)-5-ethylthiophen-2-yl)-5-methyl[1,2,4]triazol-3-ylmethyl)-5-fluoroindole-2-carboxamide.

Workup

  1. temperaturecooling
  2. customThe reaction mixture was partitioned between water and ethyl acetate
  3. washThe organic layer was washed with an aqueous citric acid solution
  4. dry with materiala saturated aqueous sodium hydrogencarbonate solution and saturated brine, and dried over magnesium sulfate
  5. customThe solvent was evaporated
  6. customthe obtained residue was crystallized from ethyl acetate

Sources & evidence

ORD record
ord-d92599df06ea4eb6b9bcf4ff5d888424
Source dataset
uspto-grants-1998_06
Patent number
US05760032

Reaction notes

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