N2,N2-dimethylpyridine-2,5-diamine → N-[6-(Dimethylamino)pyridin-3-yl]-5-trifluoromethyl-1-(3-fluorobenzyl)-1H-indole-2-carboxamide

HRID 448826

Reaction equation

HRID 448826 reaction equation
[NH2:1][C:2]1[CH:3]=[N:4][C:5]([N:8]([CH3:10])[CH3:9])=[CH:6][CH:7]=1.[F:11][C:12]([F:34])([F:33])[C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[N:18]([CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[CH:24]=1)[C:17]([C:30](O)=[O:31])=[CH:16]2.Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1>CN(C)C=O.O>[CH3:9][N:8]([CH3:10])[C:5]1[N:4]=[CH:3][C:2]([NH:1][C:30]([C:17]2[N:18]([CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[CH:24]=3)[C:19]3[C:15]([CH:16]=2)=[CH:14][C:13]([C:12]([F:33])([F:11])[F:34])=[CH:21][CH:20]=3)=[O:31])=[CH:7][CH:6]=1

Participants

7

Reactant 4

HCID 78642N2,N2-dimethylpyridine-2,5-diamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 574315325-trifluoromethyl-1-(3-fluorobenzyl)-1H-indole-2-carboxylic acid

Product 1

HCID 68932753N-[6-(Dimethylamino)pyridin-3-yl]-5-trifluoromethyl-1-(3-fluorobenzyl)-1H-indole-2-carboxamideYield 40%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

0.185 g (1.35 mmol) of 3-amino-6-(dimethylamino)pyridine (WO2005/028452) in 2 ml of dry dimethylformamide is added dropwise at 20° C. under argon to a solution of 0.35 g (1.04 mmol) of 5-trifluoromethyl-1-(3-fluorobenzyl)-1H-indole-2-carboxylic acid (WO2006/072736), 0.198 g (1.14 mmol) of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride and 0.165 g (1.14 mmol) of 1-hydroxybenzotriazole monohydrate in 6 ml of dry dimethylformamide. The reaction mixture is stirred overnight, run onto 100 ml of water and then extracted three times with 50 ml of ethyl acetate. The organic phases are subsequently combined, washed three times with 20 ml of water, dried over sodium sulfate and then concentrated under reduced pressure. The expected product is purified by chromatography on a silica column, elution being carried out with a mixture of dichloromethane and methanol. 0.19 g of the expected compound is thus isolated.

Workup

  1. extractionextracted three times with 50 ml of ethyl acetate
  2. washwashed three times with 20 ml of water
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe expected product is purified by chromatography on a silica column, elution
  6. additionbeing carried out with a mixture of dichloromethane and methanol

Sources & evidence

ORD record
ord-89c7f669a6874a82bdac977b98c3e5e8
Source dataset
uspto-grants-2013_07
Patent number
US08481745B2

Linked notes

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