Potassium Carbonate → N-(2,6-dichlorophenyl)-5-[[2-(3-methyl-1-piperidinyl)-4-(trifluoromethyl)-5-oxazolyl]carbonylamino]-1H-indole-1-carboxamide

HRID 1020369Notes

Reaction equation

HRID 1020369 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([NH:10][C:11]([C:13]3[O:17][C:16]([N:18]4[CH2:23][CH2:22][CH2:21][CH:20]([CH3:24])[CH2:19]4)=[N:15][C:14]=3[C:25]([F:28])([F:27])[F:26])=[O:12])=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[Cl:29][C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([Cl:36])[C:31]=1[N:37]=[C:38]=[O:39].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Cl:29][C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([Cl:36])[C:31]=1[NH:37][C:38]([N:1]1[C:9]2[C:4](=[CH:5][C:6]([NH:10][C:11]([C:13]3[O:17][C:16]([N:18]4[CH2:23][CH2:22][CH2:21][CH:20]([CH3:24])[CH2:19]4)=[N:15][C:14]=3[C:25]([F:27])([F:28])[F:26])=[O:12])=[CH:7][CH:8]=2)[CH:3]=[CH:2]1)=[O:39]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 6045371,3-Dichloro-2-isocyanatobenzene2×HCID 67391262N-(1H-indol-5-yl)-2-(3-methyl-1-piperidinyl)-4-(trifluoromethyl)-5-oxazolecarboxamide

Product 1

HCID 67391139N-(2,6-dichlorophenyl)-5-[[2-(3-methyl-1-piperidinyl)-4-(trifluoromethyl)-5-oxazolyl]carbonylamino]-1H-indole-1-carboxamideYield 45.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of compound 44 (0.050 g, 0.126 mmol) and 2,6-dichlorophenylisocyanate (0.025 g, 0.133 mmol) in anhydrous DMF (1.0 mL) at room temperature was added potassium carbonate (0.026 g, 0.189 mmol). The reaction mixture was stirred at room temperature for 72 h (eventually with addition of 2,6-dichlorophenyl isocyanate (0.025 g, 0.133 mmol) to drive the reaction to completion). The reaction mixture was then quenched with methanol (0.2 mL), stirred for 60 mins and concentrated. Purification of the crude residue by silica gel chromatography (eluant gradient: 100% methylene chloride to 100% EtOAc) followed by C18 reverse phase chromatography (eluant: H2O:CH3CN gradient) gave 0.033 g (45% yield) of N-(2,6-dichlorophenyl)-5-[[2-(3-methyl-1-piperidinyl)-4-(trifluoromethyl)-5-oxazolyl]carbonylamino]-1H-indole-1-carboxamide (45) as a white solid. 1H NMR (500 MHz, DMSO-d6) δ 10.18 (br s, 1H), 10.15 (br s, 1H), 8.18 (d, 1H, J=9.1 Hz), 8.10 (m, 2H), 7.66 (d, 2H, J=7.9 Hz), 7.48 (m, 2H), 6.84 (d, 1H, J=3.5 Hz), 4.13 (m, 2H), 3.06 (t, 1H, J=12.0 Hz), 2.76 (t, 1H, J=11.6 Hz), 1.72 (m, 3H), 1.54 (m, 1H), 1.15 (m, 1H), 0.94 (d, 3H, J=6.5 Hz). MS (M+1): 580/582.

Workup

  1. customthe reaction to completion)
  2. customThe reaction mixture was then quenched with methanol (0.2 mL)
  3. stirringstirred for 60 mins
  4. concentrationconcentrated
  5. customPurification of the crude residue by silica gel chromatography (eluant gradient: 100% methylene chloride to 100% EtOAc)

Sources & evidence

ORD record
ord-4828793a940449c281dae2bab22c148f
Source dataset
uspto-grants-2014_05
Patent number
US08716312B2

Reaction notes

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