Thiophenol → 2-[1-(4-Ethoxy-2,6-difluorobenzyl)-1,4,5,6-tetrahydrocyclopenta-[c]pyrazol-3-yl]-4-(pyridin-4-ylamino)pyrimidin-5-ol

HRID 1482932Notes

Reaction equation

HRID 1482932 reaction equation
[CH2:1]([O:3][C:4]1[CH:33]=[C:32]([F:34])[C:7]([CH2:8][N:9]2[C:13]3[CH2:14][CH2:15][CH2:16][C:12]=3[C:11]([C:17]3[N:22]=[C:21]([NH:23][C:24]4[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=4)[C:20]([O:30]C)=[CH:19][N:18]=3)=[N:10]2)=[C:6]([F:35])[CH:5]=1)[CH3:2].C(=O)([O-])[O-].[K+].[K+].C1(S)C=CC=CC=1>CN1CCCC1=O>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([F:35])[C:7]([CH2:8][N:9]2[C:13]3[CH2:14][CH2:15][CH2:16][C:12]=3[C:11]([C:17]3[N:22]=[C:21]([NH:23][C:24]4[CH:25]=[CH:26][N:27]=[CH:28][CH:29]=4)[C:20]([OH:30])=[CH:19][N:18]=3)=[N:10]2)=[C:32]([F:34])[CH:33]=1)[CH3:2]

Participants

5

Reactant 3

HCID 7969ThiophenolHCID 11430Potassium CarbonateHCID 722022542-[1-[(4-ethoxy-2,6-difluorophenyl)methyl]-5,6-dihydro-4H-cyclopenta[c]pyrazol-3-yl]-5-methoxy-N-pyridin-4-ylpyrimidin-4-amine

Product 1

HCID 1362464902-[1-(4-Ethoxy-2,6-difluorobenzyl)-1,4,5,6-tetrahydrocyclopenta-[c]pyrazol-3-yl]-4-(pyridin-4-ylamino)pyrimidin-5-ol

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
150 °C

Procedure

461 mg of 2-[1-(4-ethoxy-2,6-difluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[c]-pyrazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amine 2-1-1 (0.964 mmol, 1.00 eq.) were dissolved in 42 mL of dry 1-methylpyrrolidin-2-one. 51 mg of potassium carbonate (0.366 mmol, 0.38 eq.) and 150 μL benzenethiol (1.45 mmol, 1.5 eq.) were added. The mixture was stirred for 1 h at 150° C. bath temperature. The reaction mixture was partitioned between aqueous half saturated ammonium chloride solution and DCM/isopropanol (4:1). The separated aqueous layer was extracted twice with DCM/isopropanol (4:1). The combined organic layers were dried over magnesium sulfate and concentrated in vacuo. The purification of the residue by flash chromatography provided 349 mg (0.75 mmol, 78%) of analytically pure target compound.

Workup

  1. customThe reaction mixture was partitioned between aqueous half saturated ammonium chloride solution and DCM/isopropanol (4:1)
  2. extractionThe separated aqueous layer was extracted twice with DCM/isopropanol (4:1)
  3. dry with materialThe combined organic layers were dried over magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe purification of the residue by flash chromatography
  6. customprovided 349 mg (0.75 mmol, 78%) of analytically pure target compound

Sources & evidence

ORD record
ord-f5a65d3cc91f4c648489ab6523846554
Source dataset
uspto-grants-2016_08
Patent number
US09416125B2

Reaction notes

Loading…