Dimethylformamide → HCID 66905409, compound

HRID 1967474Notes

Reaction equation

HRID 1967474 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]([OH:21])=O)=[CH:5]2.C[N:23](C)[CH2:24][CH2:25][CH2:26][N:27]=[C:28]=[N:29][CH2:30][CH3:31].[CH2:33]([N:35](CC)[CH2:36]C)C.[CH3:40]N(C)C=O>>[N:35]1[CH:36]=[C:24]([NH:23][C:19]([C:6]2[N:7]([CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=3)[C:8]3[C:4]([CH:5]=2)=[CH:3][C:2]([F:1])=[CH:10][CH:9]=3)=[O:21])[CH:25]=[C:26]2[N:27]=[C:28]3[CH2:40][CH2:31][CH2:30][N:29]3[C:33]=12

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 574315135-fluoro-1-(3-fluorobenzyl)-1H-indole-2-carboxylic acid

Product 1

HCID 66905409HCID 66905409, compound

Conditions

Temperature
20 °C

Procedure

A solution of 0.5 g (1.74 mmol) of 5-fluoro-1-(3-fluorobenzyl)-1H-indole-2-carboxylic acid, prepared in sep 1.1, 0.33 g (1.74 mmol) of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide and 0.23 g (1.74 mmol) of N-1-hydroxybenzotriazole in 10 ml of dimethylformamide is stirred at 20° C. for 15 minutes. The reaction mixture is subsequently admixed with 0.516 g (2.09 mmol) of the compound IV-a and also with 0.29 ml (2.09 mmol) of triethylamine. The reaction mixture is subsequently stirred at 20° C. for 12 hours and then concentrated under reduced pressure, poured into 50 ml of water and extracted with three times 50 ml of ethyl acetate. The organic phases are combined and then washed with twice 20 ml of saturated sodium hydrogen carbonate solution, once with 20 ml of water and then once with 50 ml of saturated sodium chloride solution, dried over sodium sulfate and then concentrated under reduced pressure. The product obtained is purified by chromatography on a silica column, eluting with a mixture of dichloromethane and methanol. This gives 0.31 g of the expected compound.

Workup

  1. stirringThe reaction mixture is subsequently stirred at 20° C. for 12 hours
  2. concentrationconcentrated under reduced pressure
  3. additionpoured into 50 ml of water
  4. extractionextracted with three times 50 ml of ethyl acetate
  5. washwashed with twice 20 ml of saturated sodium hydrogen carbonate solution, once with 20 ml of water
  6. dry with materialonce with 50 ml of saturated sodium chloride solution, dried over sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe product obtained
  9. customis purified by chromatography on a silica column
  10. washeluting with a mixture of dichloromethane and methanol

Sources & evidence

ORD record
ord-da409a1fd4534fc99fd6e8107d234f89
Source dataset
uspto-grants-2013_04
Patent number
US08420817B2

Reaction notes

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