Thiophenol → HCID 136229286, compound

HRID 1774538Notes

Reaction equation

HRID 1774538 reaction equation
[CH:1]1([C:4]2[N:8]([CH2:9][C:10]3[C:15]([F:16])=[CH:14][C:13]([O:17][CH2:18][CH3:19])=[CH:12][C:11]=3[F:20])[N:7]=[C:6]([C:21]3[N:26]=[C:25]([NH:27][C:28]4[CH:33]=[CH:32][N:31]=[CH:30][CH:29]=4)[C:24]([O:34]C)=[CH:23][N:22]=3)[C:5]=2[CH3:36])[CH2:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].C1(S)C=CC=CC=1>CN1CCCC1=O>[CH:1]1([C:4]2[N:8]([CH2:9][C:10]3[C:11]([F:20])=[CH:12][C:13]([O:17][CH2:18][CH3:19])=[CH:14][C:15]=3[F:16])[N:7]=[C:6]([C:21]3[N:26]=[C:25]([NH:27][C:28]4[CH:29]=[CH:30][N:31]=[CH:32][CH:33]=4)[C:24]([OH:34])=[CH:23][N:22]=3)[C:5]=2[CH3:36])[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 7969Thiophenol2×HCID 11430Potassium Carbonate2×HCID 71611462HCID 71611462, compound

Product 1

HCID 136229286HCID 136229286, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
150 °C

Procedure

310 mg of 2-[5-cyclopropyl-1-(4-ethoxy-2,6-difluorobenzyl)-4-methyl-1H-pyrazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amine 2-1-12 (0.629 mmol, 1 eq.) were dissolved in 27.2 mL of dry 1-methylpyrrolidin-2-one. 348 mg of potassium carbonate (2.52 mmol, 4.0 eq.), molecular sieve and 97 μL benzenethiol (0.944 mmol, 1.5 eq.) were added. The mixture was stirred for 1 hour at 150° C. bath temperature. 348 mg of potassium carbonate (2.52 mmol, 4.0 eq.) and 97 μL benzenethiol (0.944 mmol, 1.5 eq.) were added again and the mixture was stirred for a further hour at 150° C. bath temperature. Then the reaction mixture was partitioned between aqueous half saturated ammonium chloride solution and ethyl acetate. The separated aqueous layer was extracted twice with ethyl acetate. The combined organic layers were dried over a silicone filter and concentrated in vacuo. The purification of the residue by flash chromatography provided 191 mg (0.36 mmol, 56%) of analytically pure target compound.

Workup

  1. stirringthe mixture was stirred for a further hour at 150° C. bath temperature
  2. customThen the reaction mixture was partitioned between aqueous half saturated ammonium chloride solution and ethyl acetate
  3. extractionThe separated aqueous layer was extracted twice with ethyl acetate
  4. dry with materialThe combined organic layers were dried over a silicone
  5. filtrationfilter
  6. concentrationconcentrated in vacuo
  7. customThe purification of the residue by flash chromatography
  8. customprovided 191 mg (0.36 mmol, 56%) of analytically pure target compound

Sources & evidence

ORD record
ord-7b0678bdbf2843229390ab12eacdecf9
Source dataset
uspto-grants-2016_02
Patent number
US09260412B2

Reaction notes

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