Aniline → 5-(6-Phenylcarbamoyl-pyrimidin-4-yloxy)-2,3-dihydro-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide

HRID 2264612Notes

Reaction equation

HRID 2264612 reaction equation
[F:1][C:2]([F:32])([F:31])[C:3]1[CH:4]=[C:5]([NH:9][C:10]([N:12]2[C:20]3[C:15](=[CH:16][C:17]([O:21][C:22]4[N:27]=[CH:26][N:25]=[C:24]([C:28](O)=[O:29])[CH:23]=4)=[CH:18][CH:19]=3)[CH2:14][CH2:13]2)=[O:11])[CH:6]=[CH:7][CH:8]=1.C(OP(C#N)(=O)OCC)C.[NH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>CN(C=O)C.CCOC(C)=O.C([O-])(O)=O.[Na+]>[F:1][C:2]([F:32])([F:31])[C:3]1[CH:4]=[C:5]([NH:9][C:10]([N:12]2[C:20]3[C:15](=[CH:16][C:17]([O:21][C:22]4[CH:23]=[C:24]([C:28](=[O:29])[NH:43][C:44]5[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=5)[N:25]=[CH:26][N:27]=4)=[CH:18][CH:19]=3)[CH2:14][CH2:13]2)=[O:11])[CH:6]=[CH:7][CH:8]=1

Participants

7

Reactant 3

HCID 6115AnilineHCID 76257Diethyl cyanophosphonate2×HCID 59596375HCID 59596375, compound

Product 1

HCID 595963495-(6-Phenylcarbamoyl-pyrimidin-4-yloxy)-2,3-dihydro-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To an ice-cooled solution of 400 mg (0.90 mMol) 6-[1-(3-trifluoromethyl-phenylcarbamoyl)-2,3-dihydro-1H-indol-5-yloxy]-pyrimidine-4-carboxylic acid in 4 ml DMF, 402 μl (2.7 mMol) diethyl-cyanophosphonate and 248 μl (2.7 mMol) aniline are added. After stirring the solution for 3 h at rt, another 402 μl diethyl-cyanophosphonate are added and stirring continued for 16 h. Then the mixture is diluted with EtOAc and sat. NaHCO3, the aqueous layer separeted off and extracted twice with EtOAc. The organic phases are washed with water and brine, dried (Na2SO4) and partially concentrated until crystals are formed. These are filtered and washed with EtOAC/DIPE, yielding the title compound: m.p.: 227-229° C.; MS: [M−1]=518; HPLC: AtRet=17.2.

Workup

  1. additionare added
  2. stirringstirring
  3. waitcontinued for 16 h
  4. extractionextracted twice with EtOAc
  5. washThe organic phases are washed with water and brine
  6. dry with materialdried (Na2SO4)
  7. concentrationpartially concentrated until crystals
  8. customare formed
  9. filtrationThese are filtered
  10. washwashed with EtOAC/DIPE

Sources & evidence

ORD record
ord-fa72f1fdde634e7ab994933aa8a8f49d
Source dataset
uspto-grants-2010_12
Patent number
US07855215B2

Reaction notes

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