Phosphoric Acid → HCID 178458655、化合物

HRID 1641389ノート

反応式

HRID 1641389 の反応式
[Cl:1][C:2]1[C:3]([NH:18][C:19]2[CH:23]=[C:22]([O:24][CH:25]([CH3:27])[CH3:26])[NH:21][N:20]=2)=[N:4][C:5]([NH:8][C@H:9]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][N:12]=2)[CH3:10])=[N:6][CH:7]=1.[P:28](=[O:32])([OH:31])([OH:30])[OH:29]>CO>[P:28]([OH:32])([OH:31])([OH:30])=[O:29].[Cl:1][C:2]1[C:3]([NH:18][C:19]2[CH:23]=[C:22]([O:24][CH:25]([CH3:27])[CH3:26])[NH:21][N:20]=2)=[N:4][C:5]([NH:8][C@H:9]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][N:12]=2)[CH3:10])=[N:6][CH:7]=1

参加物

4

反応物 2

HCID 1004Phosphoric AcidHCID 178458654HCID 178458654、化合物

生成物 1

HCID 178458655HCID 178458655、化合物

試薬・触媒・溶媒 1

HCID 887Methanol溶媒3 回

実験手順

To a solution of 5-chloro-N2-[(1S)-1-(5-fluoropyridin-2-yl)ethyl]-N4-(5-isopropoxy-1H-pyrazol-3-yl)pyrimidine-2,4-diamine (Example 6; 2.46 g, 6.28 mmol) in methanol (25 ml) was added a solution of phosphoric acid (85 wt % in water, 724 mg, 6.28 mmol) in methanol (10 ml). The resulting precipitate was heated to reflux and more methanol (25 ml) was added. The precipitate was allowed to stir at reflux for 1 hour before cooling down to room temperature. The solution was filtered and filter cake obtained was washed with methanol and transferred to a round bottomed-flask for recrystallization. A suspension of the salt in methanol (50 ml) was then heated to reflux. At reflux, methanol (125 ml) was added where dissolution occurred. The excess solvent was removed by distillation to a final volume of 75 ml. The flask was removed from the heat and the solution was allowed to cool to room temperature. The resulting precipitate was filtered, washed with methanol, and vacuum dried under N2 atmosphere (16 h) to afford 1.43 g (57% isolated yield) of the title compound. 1H NMR: 9.63 (s, 1H), 8.49 (s, 1H), 7.87-8.10 (m, 2H), 7.65 (t, J=8.67 Hz, 1H), 7.41 (dd, J=8.29, 4.52 Hz, 1H), 5.52 (s, 1H), 5.03 (br s, 1H), 4.65 (br s, 1H), 1.44 (d, J=6.78 Hz, 3H), 1.26 (d, J=6.03 Hz, 6H).

後処理

  1. temperatureThe resulting precipitate was heated
  2. temperatureto reflux
  3. temperatureat reflux for 1 hour
  4. filtrationThe solution was filtered
  5. filtrationfilter cake
  6. customobtained
  7. washwas washed with methanol
  8. customtransferred to a round bottomed-flask for recrystallization
  9. additionA suspension of the salt in methanol (50 ml)
  10. temperaturewas then heated to reflux
  11. temperatureAt reflux
  12. additionmethanol (125 ml) was added
  13. dissolutionwhere dissolution
  14. customThe excess solvent was removed by distillation to a final volume of 75 ml
  15. customThe flask was removed from the
  16. temperatureheat
  17. temperatureto cool to room temperature
  18. filtrationThe resulting precipitate was filtered
  19. washwashed with methanol, and vacuum
  20. customdried under N2 atmosphere (16 h)
  21. customto afford

出典と根拠

ORDレコード
ord-7caa2b9bf6f64050bf337c321ff69971
出典データセット
uspto-grants-2012_02
特許番号
US08114989B2

反応ノート

読み込み中…