Pyridine → N-{4-[(Dimethylamino)carbonyl]phenyl}-5-[(3,3-dimethylbutanoyl)amino]-1-(2-fluorobenzyl)-1H-indole-2-carboxamide

HRID 1825006Notes

Reaction equation

HRID 1825006 reaction equation
[CH3:1][C:2]([CH3:28])([CH3:27])[CH2:3][C:4]([NH:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[N:12]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[F:23])[C:11]([C:24](O)=[O:25])=[CH:10]2)=[O:5].N1C=CC=CC=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:59][C:60]1[CH:70]=[CH:69][C:63]([C:64]([N:66]([CH3:68])[CH3:67])=[O:65])=[CH:62][CH:61]=1>CN(C=O)C.O>[CH3:67][N:66]([CH3:68])[C:64]([C:63]1[CH:69]=[CH:70][C:60]([NH:59][C:24]([C:11]2[N:12]([CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[F:23])[C:13]3[C:9]([CH:10]=2)=[CH:8][C:7]([NH:6][C:4](=[O:5])[CH2:3][C:2]([CH3:27])([CH3:1])[CH3:28])=[CH:15][CH:14]=3)=[O:25])=[CH:61][CH:62]=1)=[O:65]

Participants

7

Reactant 4

HCID 1049PyridineHCID 2355274-Amino-N,N-dimethylbenzamideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 221446405-[(3,3-Dimethylbutanoyl)amino]-1-(2-fluorobenzyl)-1H-indole-2-carboxylic acid

Product 1

HCID 22144662N-{4-[(Dimethylamino)carbonyl]phenyl}-5-[(3,3-dimethylbutanoyl)amino]-1-(2-fluorobenzyl)-1H-indole-2-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Under argon, 200 mg (0.43 mmol) of 5-[(3,3-dimethylbutanoyl)amino]-1-(2-fluorobenzyl)-1H-indole-2-carboxylic acid (Example XXXIX) are dissolved in 2 ml of DMF, and 4 ml of pyridine are added. 489.2 mg (1.29 mmol) of HATU are added to this solution, 140.8 mg (0.86 mmol) of 4-amino-N,N-dimethylbenzamide are then slowly added dropwise and the reaction mixture is stirred at RT overnight. For work-up, water is added and the mixture is extracted repeatedly with ethyl acetate. The combined organic phases are dried over sodium sulphate and filtered, and the solvent is removed under reduced pressure. The residue is purified by preparative HPLC. This gives 47.4 mg (15% of theory) of product.

Workup

  1. additionare then slowly added dropwise
  2. extractionthe mixture is extracted repeatedly with ethyl acetate
  3. dry with materialThe combined organic phases are dried over sodium sulphate
  4. filtrationfiltered
  5. customthe solvent is removed under reduced pressure
  6. customThe residue is purified by preparative HPLC

Sources & evidence

ORD record
ord-a9602eb638114291961e5a6205cf1268
Source dataset
uspto-grants-2006_05
Patent number
US07045544B2

Reaction notes

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