Methylamine → HCID 11258991, compound

HRID 2105213Notes

Reaction equation

HRID 2105213 reaction equation
CC1C=CC(S(O[CH2:12][C:13]2[N:18]=[C:17]([N:19]3[CH2:23][CH2:22][CH2:21][CH:20]3[C:24]3[O:28][N:27]=[C:26]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=4)[CH:25]=3)[N:16]=[C:15]([NH:35][CH:36]3[CH:40]=[C:39]([CH3:41])[NH:38][N:37]3S(C3C=CC(C)=CC=3)(=O)=O)[CH:14]=2)(=O)=O)=CC=1.[CH3:52][NH2:53].C1COCC1>>[CH3:52][NH:53][CH2:12][C:13]1[N:18]=[C:17]([N:19]2[CH2:23][CH2:22][CH2:21][CH:20]2[C:24]2[O:28][N:27]=[C:26]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=3)[CH:25]=2)[N:16]=[C:15]([NH:35][C:36]2[CH:40]=[C:39]([CH3:41])[NH:38][N:37]=2)[CH:14]=1

Participants

4

Reactant 3

HCID 6329MethylamineHCID 8028TetrahydrofuranHCID 86610854HCID 86610854, compound

Product 1

HCID 11258991HCID 11258991, compoundYield 77%

Procedure

A mixture of 6-[(4-methylphenylsulphonyloxy)methyl]-2-{2-[3-(pyrid-2-yl)isoxazol-5-yl]pyrrolidin-1-yl}-4-(5-methyl-2-N-[4-methylphenylsulphonyl]-1H-pyrazol-3-ylamino)pyrimidine (Method 52) (190 mg, 0.26 mmol) and a solution of 2N methylamine in THF (5 ml, 10 mmol) were heated at 90° C. in a sealed vessel under microwave irradiation for 1 hour. The volatiles were removed by evaporation and the residue 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 of give the title compound (87.1 mg, 77%).

Workup

  1. customThe volatiles were removed by evaporation
  2. customthe residue 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

Sources & evidence

ORD record
ord-160ae946d41148e2938c985e39db71ab
Source dataset
uspto-grants-2009_08
Patent number
US07579349B2

Reaction notes

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