Cesium carbonate → 2-(4-amino-3-chloro-phenyl)-1-cyclobutyl-6-(pyrimidin-2-yloxy)-1H-indole-3-carbonitrile

HRID 1009672Notes

Reaction equation

HRID 1009672 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]([CH:20]3[CH2:23][CH2:22][CH2:21]3)[C:10]3[C:15]([C:16]=2[C:17]#[N:18])=[CH:14][CH:13]=[C:12]([OH:19])[CH:11]=3)=[CH:4][C:3]=1[Cl:24].Cl[C:26]1[N:31]=[CH:30][CH:29]=[CH:28][N:27]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]([CH:20]3[CH2:23][CH2:22][CH2:21]3)[C:10]3[C:15]([C:16]=2[C:17]#[N:18])=[CH:14][CH:13]=[C:12]([O:19][C:26]2[N:31]=[CH:30][CH:29]=[CH:28][N:27]=2)[CH:11]=3)=[CH:4][C:3]=1[Cl:24]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 744042-ChloropyrimidineHCID 594306152-(4-amino-3-chloro-phenyl)-1-cyclobutyl-6-hydroxy-1H-indole-3-carbonitrile

Product 1

HCID 594306702-(4-amino-3-chloro-phenyl)-1-cyclobutyl-6-(pyrimidin-2-yloxy)-1H-indole-3-carbonitrileYield 91.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-(4-Amino-3-chloro-phenyl)-1-cyclobutyl-6-hydroxy-1H-indole-3-carbonitrile (0.67 g, 2 mmol), prepared in step ZA, was dissolved in DMF (7 mL), followed by the addition of 2-chloro-pyrimidine (0.34 g, 3 mmol) and cesium carbonate (1.3 g, 4 mmol). The mixture was brought to 70° C. and stirred for 1 h. After cooling, the solid was filtered and washed with EtOAc. The filtrate was washed with water and brine, dried, concentrated and triturated with ether to provide 2-(4-amino-3-chloro-phenyl)-1-cyclobutyl-6-(pyrimidin-2-yloxy)-1H-indole-3-carbonitrile (0.76 g, 91%) as a white solid.

Workup

  1. customwas brought to 70° C.
  2. temperatureAfter cooling
  3. filtrationthe solid was filtered
  4. washwashed with EtOAc
  5. washThe filtrate was washed with water and brine
  6. customdried
  7. concentrationconcentrated
  8. customtriturated with ether

Sources & evidence

ORD record
ord-9155c1d4d102435487d4f5992bde18e5
Source dataset
uspto-grants-2011_07
Patent number
US07973069B2

Reaction notes

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