(Methoxycarbonylsulfamoyl)triethylammonium hydroxide → 6-(5-Methyl-[1,3,4]-oxadiazol-2-yl)-2-{2-[3-(pyrid-2-yl)isoxazol-5-yl]pyrrolidin-1-yl}-4-(5-methyl-1H-pyrazol-3-ylamino)pyrimidine

HRID 2105209Notes

Reaction equation

HRID 2105209 reaction equation
[OH-].COC(NS([N+](CC)(CC)CC)(=O)=O)=O.[C:17]([NH:20][NH:21][C:22]([C:24]1[N:29]=[C:28]([N:30]2[CH2:34][CH2:33][CH2:32][CH:31]2[C:35]2[O:39][N:38]=[C:37]([C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][N:41]=3)[CH:36]=2)[N:27]=[C:26]([NH:46][CH:47]2[CH:51]=[C:50]([CH3:52])[NH:49][N:48]2C(=O)C)[CH:25]=1)=O)(=[O:19])[CH3:18]>C1COCC1>[CH3:18][C:17]1[O:19][C:22]([C:24]2[N:29]=[C:28]([N:30]3[CH2:34][CH2:33][CH2:32][CH:31]3[C:35]3[O:39][N:38]=[C:37]([C:40]4[CH:45]=[CH:44][CH:43]=[CH:42][N:41]=4)[CH:36]=3)[N:27]=[C:26]([NH:46][C:47]3[CH:51]=[C:50]([CH3:52])[NH:49][N:48]=3)[CH:25]=2)=[N:21][N:20]=1

Participants

4

Reactant 2

HCID 11032497(Methoxycarbonylsulfamoyl)triethylammonium hydroxideHCID 68814580HCID 68814580, compound

Product 1

HCID 688159886-(5-Methyl-[1,3,4]-oxadiazol-2-yl)-2-{2-[3-(pyrid-2-yl)isoxazol-5-yl]pyrrolidin-1-yl}-4-(5-methyl-1H-pyrazol-3-ylamino)pyrimidineYield 52%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(Methoxycarbonylsulfamoyl)triethylammonium hydroxide (internal salt) (90 mg, 3.76 mmol) was added to a solution of 6-[N-(acetylamino)carbamoyl]-2-{2-[3-(pyrid-2-yl)isoxazol-5-yl]pyrrolidin-1-yl}-4-(2-acetyl-5-methyl-1H-pyrazol-3-ylamino)pyrimidine (Method 51) (500 mg, 0.94 mmol) in anhydrous THF (20 ml) and the reaction heated at reflux for 18 hours. The volatiles were removed by evaporation and the residue was dissolved in methanol (5 ml) and 2N aqueous sodium hydroxide solution (11.0 ml) and stirred at ambient temperature for 15 minutes. The methanol was removed by evaporation and the pH of the resulting solution adjusted to pH 7 with 1N hydrochloric acid. The volatiles were removed evaporation and the residue purified by chromatography on silica gel eluting with DCM/methanol (100:0 increasing in polarity to 90:10). The purified product was then triturated with diethylether and collected by filtration to give the title compound (200 mg, 52%).

Workup

  1. temperaturethe reaction heated
  2. temperatureat reflux for 18 hours
  3. customThe volatiles were removed by evaporation
  4. dissolutionthe residue was dissolved in methanol (5 ml)
  5. customThe methanol was removed by evaporation
  6. customThe volatiles were removed
  7. customevaporation
  8. customthe residue purified by chromatography on silica gel eluting with DCM/methanol (100:0 increasing in polarity to 90:10)
  9. customThe purified product was then triturated with diethylether
  10. filtrationcollected by filtration

Sources & evidence

ORD record
ord-24708e388e094403b09569a4c8c3304a
Source dataset
uspto-grants-2009_08
Patent number
US07579349B2

Reaction notes

Loading…