Water → N-(quinol-7-yl)-5-fluoro-1-[(3-fluorophenyl)methyl]-1H-indole-2-carboxamide

HRID 225803Notes

Reaction equation

HRID 225803 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=1)[C:6]([C:19](O)=[O:20])=[CH:5]2.Cl.[NH2:23][C:24]1[CH:33]=[C:32]2[C:27]([CH:28]=[CH:29][CH:30]=[N:31]2)=[CH:26][CH:25]=1.C(N(C(C)C)CC)(C)C.O>CN(C)C=O.C(OCC)(=O)C>[N:31]1[C:32]2[C:27](=[CH:26][CH:25]=[C:24]([NH:23][C:19]([C:6]3[N:7]([CH2:11][C:12]4[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=4)[C:8]4[C:4]([CH:5]=3)=[CH:3][C:2]([F:1])=[CH:10][CH:9]=4)=[O:20])[CH:33]=2)[CH:28]=[CH:29][CH:30]=1

Participants

7

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 122826527-Aminoquinoline HydrochlorideHCID 574315135-fluoro-1-(3-fluorobenzyl)-1H-indole-2-carboxylic acid

Product 1

HCID 11567803N-(quinol-7-yl)-5-fluoro-1-[(3-fluorophenyl)methyl]-1H-indole-2-carboxamideYield 36.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

1 g (1.9 mmol) of benzotriazol-1-yloxytris(pyrrolidine)phosphonium hexafluorophosphate is added, with stirring and under nitrogen, to a suspension of 0.5 g (1.74 mmol) of 5-fluoro-1-[(3-fluorophenyl)methyl]-1H-indole-2-carboxylic acid, obtained in step 11.1, in 10 ml of dry dimethylformamide. After 5 minutes, 0.4 g (1.83 mmol) of 7-aminoquinoline hydrochloride (WO 2003/049702) and 0.9 g (7 mmol) of diisopropylethylamine are added. After stirring for 2 hours at room temperature and for 2 hours at 60° C., the reaction medium is poured into 100 ml of water and 50 ml of ethyl acetate. After separation of the phases by settling and extraction of the aqueous phase, the organic phases are combined, washed with water and dried over sodium sulfate. The residue is purified by chromatography on a column of silica gel, eluting with a mixture of dichloromethane and acetone. The solid obtained is recrystallized from isopropyl alcohol. 0.26 g of solid is obtained.

Workup

  1. customAfter separation of the phases
  2. extractionextraction of the aqueous phase
  3. washwashed with water
  4. dry with materialdried over sodium sulfate
  5. customThe residue is purified by chromatography on a column of silica gel
  6. washeluting with a mixture of dichloromethane and acetone
  7. customThe solid obtained
  8. customis recrystallized from isopropyl alcohol

Sources & evidence

ORD record
ord-4320987264614ff8be4b72fe03a9dc4d
Source dataset
uspto-grants-2009_07
Patent number
US07557134B2

Reaction notes

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