Thiophenol → HCID 136271309, compound

HRID 1776405Notes

Reaction equation

HRID 1776405 reaction equation
[CH2:1]([O:3][C:4]1[CH:34]=[C:33]([F:35])[C:7]([CH2:8][N:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]([C:18]3[N:23]=[C:22]([NH:24][C:25]4[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=4)[C:21]([O:31]C)=[CH:20][N:19]=3)=[N:10]2)=[C:6]([F:36])[CH:5]=1)[CH3:2].C(=O)([O-])[O-].[K+].[K+].C1(S)C=CC=CC=1.[Cl-].[NH4+]>CN1CCCC1=O.ClCCl.C(O)(C)C>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([F:36])[C:7]([CH2:8][N:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]([C:18]3[N:23]=[C:22]([NH:24][C:25]4[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=4)[C:21]([OH:31])=[CH:20][N:19]=3)=[N:10]2)=[C:33]([F:35])[CH:34]=1)[CH3:2]

Participants

7

Reactant 4

HCID 7969ThiophenolHCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 86732433HCID 86732433, compound

Product 1

HCID 136271309HCID 136271309, compound

Reagents, catalysts & solvents 2

HCID 13387N-methyl-2-pyrrolidoneSolventHCID 21966342Isopropanol methylene chlorideSolvent

Conditions

Temperature
190 °C

Procedure

1.32 g of 2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amine (2-5-1, 2.70 mmol, 1. eq.) were dissolved in 117 ml of dry 1-methylpyrrolidin-2-one. 142 mg of potassium carbonate were added under nitrogen atmosphere. Then 0.42 ml of benzenethiol were added dropwise. The reaction mixture was stirred for an hour at 190° C. and cooled over the weekend at room temperature. Then the mixture was portioned between half saturated aq. ammonium chloride solution and dichloromethane/isopropanol 4:1. The phases were separated and the aqueous layer was extracted twice with dichloromethane/isopropanol 4:1. The combined organic layers were washed with brine, dried over a silicone filter and concentrated in vacuo. The residue was purified by flash chromatography to yield 781 mg (1.65 mmol, 60.9%) of the analytically pure target compound.

Workup

  1. temperaturecooled over the weekend at room temperature
  2. customThe phases were separated
  3. extractionthe aqueous layer was extracted twice with dichloromethane/isopropanol 4:1
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over a silicone
  6. filtrationfilter
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography
  9. customto yield 781 mg (1.65 mmol, 60.9%) of the analytically pure target compound

Sources & evidence

ORD record
ord-da7c7e3602a94233ade06d72dc6ea6dd
Source dataset
uspto-grants-2016_02
Patent number
US09265763B2

Reaction notes

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