1-Hydroxybenzotriazole → N-[6-(Dimethylamino)pyridin-3-yl]-5-trimethylsilyl-1-[(3-fluorophenyl)methyl]-1H-indole-2-carboxamide

HRID 1948791Notes

Reaction equation

HRID 1948791 reaction equation
[CH3:1][Si:2]([CH3:24])([CH3:23])[C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[CH:14]=1)[C:7]([C:20](O)=[O:21])=[CH:6]2.[NH2:25][C:26]1[CH:27]=[N:28][C:29]([N:32]([CH3:34])[CH3:33])=[CH:30][CH:31]=1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>CN(C)C=O>[CH3:33][N:32]([CH3:34])[C:29]1[N:28]=[CH:27][C:26]([NH:25][C:20]([C:7]2[N:8]([CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[CH:14]=3)[C:9]3[C:5]([CH:6]=2)=[CH:4][C:3]([Si:2]([CH3:23])([CH3:24])[CH3:1])=[CH:11][CH:10]=3)=[O:21])=[CH:31][CH:30]=1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 78642N2,N2-dimethylpyridine-2,5-diamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 581009535-trimethylsilyl-1-[(3-fluorophenyl)methyl]-1H-indole-2-carboxylic acid

Product 1

HCID 66851043N-[6-(Dimethylamino)pyridin-3-yl]-5-trimethylsilyl-1-[(3-fluorophenyl)methyl]-1H-indole-2-carboxamideYield 49.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Compound No. 7 was prepared according to a process similar to that described in stage 5.4, by reacting 0.3 g (0.88 mmol) of 5-trimethylsilyl-1-[(3-fluorophenyl)methyl]-1H-indole-2-carboxylic acid, prepared according to the protocol described in stage 3.6, with 181 mg (1.32 mmol) of 3-amino-6-(dimethylamino)pyridine in the presence of 185 mg (0.97 mmol) of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDAC) and of 131 mg (0.97 mmol) of 1-hydroxybenzotriazole (HOBT) in 10 ml of dimethylformamide. The product obtained is purified by silica column chromatography, elution being carried out with a mixture of dichloromethane and acetone. The solid obtained after evaporation of the solvent under reduced pressure is recrystallized from isopropyl alcohol. 200 mg of the expected product are thus isolated.

Workup

  1. custom7 was prepared
  2. customprepared
  3. customThe product obtained
  4. customis purified by silica column chromatography, elution
  5. additionbeing carried out with a mixture of dichloromethane and acetone
  6. customThe solid obtained
  7. customafter evaporation of the solvent under reduced pressure
  8. customis recrystallized from isopropyl alcohol

Sources & evidence

ORD record
ord-99ce549b915f47c89c95659d2e0e5822
Source dataset
uspto-grants-2013_03
Patent number
US08399491B2

Reaction notes

Loading…