Dicyclohexylcarbodiimide → N-[6-(Acetylamino)pyridin-3-yl]-5-fluoro-1-(3-fluorobenzyl)-1H-indole-2-carboxamide

HRID 1943988Notes

Reaction equation

HRID 1943988 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.C1(N=C=NC2CCCCC2)CCCCC1.O.ON1C2C=CC=CC=2N=N1.[C:48]([NH:51][C:52]1[CH:57]=[CH:56][C:55]([NH2:58])=[CH:54][N:53]=1)(=[O:50])[CH3:49]>CN(C=O)C.C([O-])(O)=O.[Na+].C(OCC)(=O)C.CN(C1C=CC=CN=1)C>[C:48]([NH:51][C:52]1[N:53]=[CH:54][C:55]([NH:58][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:56][CH:57]=1)(=[O:50])[CH3:49]

Participants

9

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 27352192-Acetamido-5-aminopyridineHCID 27960291-Hydroxybenzotriazole hydrateHCID 574315135-fluoro-1-(3-fluorobenzyl)-1H-indole-2-carboxylic acid

Product 1

HCID 66863369N-[6-(Acetylamino)pyridin-3-yl]-5-fluoro-1-(3-fluorobenzyl)-1H-indole-2-carboxamideYield 88.9%

Reagents, catalysts & solvents 4

HCID 218852-DimethylaminopyridineCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution, stirred at 20° C. under an inert atmosphere, of 2 g (6.96 mmol) of 5-fluoro-1-[(3-fluorophenyl)methyl]-1H-indole-2-carboxylic acid, prepared according to the protocol described in step 1.1, in 40 mL of DMF are added 1.72 g (8.35 mmol) of dicyclohexylcarbodiimide (DCC) and 1.13 g (8.35 mmol) of 1-hydroxybenzotriazole hydrate (HOBT). The reaction mixture is stirred at room temperature for 30 minutes. 2.1 g (13.92 mmol) of 2-acetamido-5-aminopyridine and 20 mg of dimethylaminopyridine (DMAP) are then added to the reaction mixture. After stirring for 24 hours at 20° C., the reaction mixture is concentrated to dryness. The residue obtained is taken up in a mixture of 200 mL of saturated aqueous NaHCO3 solution and 200 mL of ethyl acetate. The phases are separated by settling and the aqueous phase is extracted with 200 mL of ethyl acetate. The combined organic phases are dried over sodium sulfate and then concentrated under reduced pressure. A solid is collected, and is purified by chromatography on a column of silica, eluting with a mixture of dichloromethane and methanol. 2.6 g of the expected product are thus obtained.

Workup

  1. customprepared
  2. stirringAfter stirring for 24 hours at 20° C.
  3. concentrationthe reaction mixture is concentrated to dryness
  4. customThe residue obtained
  5. customThe phases are separated
  6. extractionthe aqueous phase is extracted with 200 mL of ethyl acetate
  7. dry with materialThe combined organic phases are dried over sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customA solid is collected
  10. customis purified by chromatography on a column of silica
  11. washeluting with a mixture of dichloromethane and methanol

Sources & evidence

ORD record
ord-5a16986b183e4acb8a0cecbf8b252d76
Source dataset
uspto-grants-2013_03
Patent number
US08394820B2

Reaction notes

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