Morpholine → HCID 11202857, compound

HRID 2105204Notes

Reaction equation

HRID 2105204 reaction equation
CO[C:3]([C:5]1[N:10]=[C:9]([N:11]2[CH2:15][CH2:14][CH2:13][CH:12]2[C:16]2[O:20][N:19]=[C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=3)[CH:17]=2)[N:8]=[C:7]([NH:27][C:28]2[CH:32]=[C:31]([CH3:33])[NH:30][N:29]=2)[CH:6]=1)=[O:4].[NH:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1>CO>[O:37]1[CH2:38][CH2:39][N:34]([C:3]([C:5]2[N:10]=[C:9]([N:11]3[CH2:15][CH2:14][CH2:13][CH:12]3[C:16]3[O:20][N:19]=[C:18]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=4)[CH:17]=3)[N:8]=[C:7]([NH:27][C:28]3[CH:32]=[C:31]([CH3:33])[NH:30][N:29]=3)[CH:6]=2)=[O:4])[CH2:35][CH2:36]1

Participants

4

Reactant 2

HCID 8083MorpholineHCID 113053826-Methoxycarbonyl-2-{2-[3-(pyrid-2-yl)isoxazol-5-yl]pyrrolidin-1-yl}-4-(5-methyl-1H-pyrazol-3-ylamino)pyrimidine

Product 1

HCID 11202857HCID 11202857, compoundYield 53.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 6-methoxycarbonyl-2-{2-[3-(pyrid-2-yl)isoxazol-5-yl]pyrrolidin-1-yl}-4-(5-methyl-1H-pyrazol-3-ylamino)pyrimidine (Example 56) (200 mg, 0.45 mmol) and morpholine (0.5 ml, 5.73 mmol) in anhydrous methanol (5.0 ml) was heated at 120° C. for 18 hours. The volatiles were removed by evaporation and the residue was purified by reverse phase HPLC using a C18 column eluting with water/acetonitrile/TFA (95:5:0.2 decreasing in polarity to 0:100:0.2). Product containing fractions were combined and passed through a 50 g isolute SCX-2 ion exchange column. The column was eluted with methanol to elute any neutrals, followed by 7M methanolic ammonia to elute the product. The solvent was removed by evaporation and the residue was triturated with diethylether. The resulting solid was collected by filtration to give the title compound (120 mg, 52%).

Workup

  1. customThe volatiles were removed by evaporation
  2. customthe residue was purified by reverse phase HPLC
  3. washeluting with water/acetonitrile/TFA (95:5:0.2 decreasing in polarity to 0:100:0.2)
  4. additionProduct containing fractions
  5. washThe column was eluted with methanol
  6. washto elute any neutrals
  7. washto elute the product
  8. customThe solvent was removed by evaporation
  9. customthe residue was triturated with diethylether
  10. filtrationThe resulting solid was collected by filtration

Sources & evidence

ORD record
ord-9b306e4e18cd4147a868ca7ddee4e878
Source dataset
uspto-grants-2009_08
Patent number
US07579349B2

Reaction notes

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