Methanol → 6-Methoxycarbonyl-2-{2-[3-(pyrid-2-yl)isoxazol-5-yl]pyrrolidin-1-yl}-4-(5-methyl-1H-pyrazol-3-ylamino)pyrimidine

HRID 2105202Notes

Reaction equation

HRID 2105202 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[CH:11]=[C:10]([CH:12]2[CH2:16][CH2:15][CH2:14][N:13]2[C:17]2[N:22]=[C:21]([NH:23][C:24]3[CH:28]=[C:27]([CH3:29])[NH:26][N:25]=3)[CH:20]=[C:19]([C:30]([OH:32])=[O:31])[N:18]=2)[O:9][N:8]=1.S(=O)(=O)(O)O.[CH3:38]O>>[CH3:38][O:31][C:30]([C:19]1[N:18]=[C:17]([N:13]2[CH2:14][CH2:15][CH2:16][CH:12]2[C:10]2[O:9][N:8]=[C:7]([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)[CH:11]=2)[N:22]=[C:21]([NH:23][C:24]2[CH:28]=[C:27]([CH3:29])[NH:26][N:25]=2)[CH:20]=1)=[O:32]

Participants

4

Reactant 3

HCID 887MethanolHCID 1118Sulfuric AcidHCID 68813756HCID 68813756, compound

Product 1

HCID 113053826-Methoxycarbonyl-2-{2-[3-(pyrid-2-yl)isoxazol-5-yl]pyrrolidin-1-yl}-4-(5-methyl-1H-pyrazol-3-ylamino)pyrimidineYield 51%

Procedure

A mixture of 2-{2-[3-(pyrid-2-yl)isoxazol-5-yl]pyrrolidin-1-yl}-4-(5-methyl-1H-pyrazol-3-ylamino)pyrimidin-6-yl carboxylic acid (Method 43) (1.73 g, 4.0 mmol), methanol (300 ml) and 98% sulphuric acid (1 ml) was heated at reflux for 18 hours. The volatiles were removed by evaporation, the residue dissolved in water and the pH of the resulting solution adjusted to pH 12 with 10M sodium hydroxide. The aqueous solution was extracted with DCM and purified by chromatography on silica gel, eluting with DCM/methanol (100:0 increasing in polarity to 90:10) to give the title compound (904 mg, 51%).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 18 hours
  3. customThe volatiles were removed by evaporation
  4. dissolutionthe residue dissolved in water
  5. extractionThe aqueous solution was extracted with DCM
  6. custompurified by chromatography on silica gel
  7. washeluting with DCM/methanol (100:0 increasing in polarity to 90:10)

Sources & evidence

ORD record
ord-522127e1d10e40029bb87a59c930f0f2
Source dataset
uspto-grants-2009_08
Patent number
US07579349B2

Reaction notes

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