Pyrrolidine → HCID 11453887, compound

HRID 2105215Notes

Reaction equation

HRID 2105215 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:12][CH2:11][CH2:10][CH:9]2[C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=3)[CH:14]=2)[N:5]=[C:4]([NH:24][C:25]2[CH:29]=[C:28]([CH3:30])[NH:27][N:26]=2)[CH:3]=1.[NH:31]1[CH2:35][CH2:34][CH2:33][CH2:32]1>O1CCOCC1>[N:31]1([C:2]2[N:7]=[C:6]([N:8]3[CH2:12][CH2:11][CH2:10][CH:9]3[C:13]3[O:17][N:16]=[C:15]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=4)[CH:14]=3)[N:5]=[C:4]([NH:24][C:25]3[CH:29]=[C:28]([CH3:30])[NH:27][N:26]=3)[CH:3]=2)[CH2:35][CH2:34][CH2:33][CH2:32]1

Participants

4

Reactant 2

HCID 31268PyrrolidineHCID 11281654HCID 11281654, compound

Product 1

HCID 11453887HCID 11453887, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 6-chloro-4-(5-methyl-1H-pyrazol-3-ylamino)-2-{2-[3-(pyrid-2-yl)isoxazol-5-yl]pyrrolidin-1-yl}pyrimidine (Example 17) (250 mg, 0.59 mmol), pyrrolidine (0.5 ml, 5.98 mmol) and anhydrous 1,4-dioxane (5.0 ml) was heated at 100° C. in a sealed vessel under microwave irradiation for 1 hour. 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 triturated with diethylether and collected by filtration to give the title compound (145 mg, 54%).

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 triturated with diethylether
  10. filtrationcollected by filtration

Sources & evidence

ORD record
ord-dc62120e03a14efab04c0b99c5791aa6
Source dataset
uspto-grants-2009_08
Patent number
US07579349B2

Reaction notes

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