Ethanolamine → HCID 11340490, compound

HRID 2105198Notes

Reaction equation

HRID 2105198 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].[CH2:34]([CH2:36][NH2:37])[OH:35]>CO>[OH:35][CH2:34][CH2:36][NH:37][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]

Participants

4

Reactant 2

HCID 700EthanolamineHCID 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 11340490HCID 11340490, compoundYield 57%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
88 °C

Procedure

A mixture of 6-methoxycarbonyl-4-(5-methyl-1H-pyrazol-3-ylamino)-2-{2-[3-(pyrid-2-yl)isoxazol-5-yl]pyrrolidin-1-yl}pyrimidine (Example 45) (49.5 mg, 0.11 mmol) and ethanolamine (2.0 ml, 33.7 mmol) in methanol (4 ml) was heated at 88° C. for 2 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) the fractions containing product were combined and passed through a 50 g isolute SCX-2 ion exchange column. The column was eluted with methanol to elute any neutral impurities, followed by 7M methanolic ammonia to elute the product. The solvent was removed by evaporation, the residue triturated with diethylether and the resulting solid collected by filtration to give the title compound (27 mg, 57%).

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) the fractions
  4. additioncontaining product
  5. washThe column was eluted with methanol
  6. washto elute any neutral impurities
  7. washto elute the product
  8. customThe solvent was removed by evaporation
  9. customthe residue triturated with diethylether
  10. filtrationthe resulting solid collected by filtration

Sources & evidence

ORD record
ord-10ddcea6802e4e9caf384da5aa2bd0f5
Source dataset
uspto-grants-2009_08
Patent number
US07579349B2

Reaction notes

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