Tetrahydrofuran → 2-(5-cyclopropyl-4-methyl-1H-pyrazol-3-yl)-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amine

HRID 1484678Notes

Reaction equation

HRID 1484678 reaction equation
[CH:1]1([C:4]2[N:8](CC3C=CC=CC=3F)[N:7]=[C:6]([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][CH3:31])=[CH:19][N:18]=3)[C:5]=2[CH3:32])[CH2:3][CH2:2]1.CC([O-])(C)C.[K+].C1COCC1>CS(C)=O.CC(O)(C)C>[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([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][CH3:31])=[CH:19][N:18]=3)[C:5]=2[CH3:32])[CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 23665647Potassium tert-butoxideHCID 716113222-[5-cyclopropyl-1-(2-fluorobenzyl)-4-methyl-1H-pyrazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amine

Product 1

HCID 896490232-(5-cyclopropyl-4-methyl-1H-pyrazol-3-yl)-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amine

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6386tert-ButanolSolvent

Procedure

410 mg of 2-[5-cyclopropyl-1-(2-fluorobenzyl)-4-methyl-1H-pyrazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amine 2-1-10 (0.952 mmol, 1.0 eq.) were dissolved in 1.1 mL of dry dimethyl sulfoxide and 1.4 mL of dry 2-methylpropan-2-ol. 6.56 mL of 1M potassium 2-methylpropan-2-olate in THF (6.56 mmol, 6.9 eq.) were added. The mixture was flushed three times with oxygen and stirred for 5 hours at rt. Then the reaction mixture was partitioned between aqueous saturated ammonium chloride solution and ethyl acetate. The separated aqueous layer was extracted three times with ethyl acetate. The combined organic layers were dried over sodium sulfate and concentrated in vacuo. The purification of the residue by flash chromatography provided 200 mg (0.62 mmol, 65.1%) of analytically pure target compound.

Workup

  1. customThe mixture was flushed three times with oxygen
  2. customThen the reaction mixture was partitioned between aqueous saturated ammonium chloride solution and ethyl acetate
  3. extractionThe separated aqueous layer was extracted three times with ethyl acetate
  4. dry with materialThe combined organic layers were dried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe purification of the residue by flash chromatography
  7. customprovided 200 mg (0.62 mmol, 65.1%) of analytically pure target compound

Sources & evidence

ORD record
ord-b83e436953b44b37b4a03aaeda569416
Source dataset
uspto-grants-2016_08
Patent number
US09422268B2

Reaction notes

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