Phosphoric Acid → HCID 178458655, 화합물

HRID 1641389노트

반응식

HRID 1641389 반응식
[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

참가 물질

4

반응물 2

HCID 1004Phosphoric AcidHCID 178458654HCID 178458654, 화합물

생성물 1

HCID 178458655HCID 178458655, 화합물

시약·촉매·용매 1

HCID 887Methanol용매3회

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-7caa2b9bf6f64050bf337c321ff69971
출처 데이터셋
uspto-grants-2012_02
특허 번호
US08114989B2

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