홈MCP워크벤치Skills
홈워크벤치알림마이페이지
llms.txt · MCP 가이드개인정보처리방침 · 이용약관 · 지원v1.8.0
  1. 홈
  2. /반응

Dichloromethane → 6-tert-butyl-8-fluoro-2-(2-hydroxymethyl-3-{5-[5-(4-isopropyl-piperazin-1-yl)-pyridin-2-ylamino]-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl}-phenyl)-2H-phthalazin-1-one HCl

HRID 1431104
노트
인쇄 미리보기

반응식

HRID 1431104 반응식
C([O:4][CH2:5][C:6]1[C:11]([C:12]2[CH:17]=[C:16]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([N:25]4[CH2:30][CH2:29][N:28]([CH:31]([CH3:33])[CH3:32])[CH2:27][CH2:26]4)=[CH:21][N:20]=3)[C:15](=[O:34])[N:14]([CH3:35])[N:13]=2)=[CH:10][CH:9]=[CH:8][C:7]=1[N:36]1[N:45]=[CH:44][C:43]2[C:38](=[C:39]([F:50])[CH:40]=[C:41]([C:46]([CH3:49])([CH3:48])[CH3:47])[CH:42]=2)[C:37]1=[O:51])(=O)C.[OH-].[Na+].C(Cl)[Cl:55]>C1COCC1.C([O-])(O)=O.[Na+]>[ClH:55].[C:46]([C:41]1[CH:42]=[C:43]2[C:38](=[C:39]([F:50])[CH:40]=1)[C:37](=[O:51])[N:36]([C:7]1[CH:8]=[CH:9][CH:10]=[C:11]([C:12]3[CH:17]=[C:16]([NH:18][C:19]4[CH:24]=[CH:23][C:22]([N:25]5[CH2:26][CH2:27][N:28]([CH:31]([CH3:32])[CH3:33])[CH2:29][CH2:30]5)=[CH:21][N:20]=4)[C:15](=[O:34])[N:14]([CH3:35])[N:13]=3)[C:6]=1[CH2:5][OH:4])[N:45]=[CH:44]2)([CH3:48])([CH3:49])[CH3:47]
참가 물질반응 조건실험 절차후처리출처 및 근거반응 노트

참가 물질

6

반응물 3

HCID 6344DichloromethaneHCID 14798Sodium HydroxideHCID 667431912-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(5-(5-(4-isopropylpiperazin-1-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)benzyl acetate

생성물 1

HCID 667424336-tert-butyl-8-fluoro-2-(2-hydroxymethyl-3-{5-[5-(4-isopropyl-piperazin-1-yl)-pyridin-2-ylamino]-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl}-phenyl)-2H-phthalazin-1-one HCl수율 38%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 516892Sodium Bicarbonate용매

반응 조건

온도
60 °C

실험 절차

To 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(5-(5-(4-isopropylpiperazin-1-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)benzyl acetate (153 mg, 220 μmol, Eq: 1.00) in THF (2.0 ml) was added an aqueous solution of 1N NaOH (2.0 mL, 2.00 mmol, Eq: 9.08). The resulting solution heated at 60° C. for 2 h. The mixture was cooled to room temperature. The solution was diluted with saturated NaHCO3 and DCM. The layers were separated. The aqueous layer was extracted three times with DCM. The combined organics were dried over MgSO4. The solution was filtered. Concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 12 g, 0% to 50% (60:10:1 DCM:MeOH:NH4OH)/DCM gradient) to give a cream solid. The solid was triturated with Et2O. The solid was filtered, then dissolved in 2 ml DCM. A solution of 1.0 M HCl in Et2O (2 ml) was added. A solid formed. The solid was filtered and dried under vacuum to give 6-tert-butyl-8-fluoro-2-(2-hydroxymethyl-3-{5-[5-(4-isopropyl-piperazin-1-yl)-pyridin-2-ylamino]-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl}-phenyl)-2H-phthalazin-1-one HCl (57.5 mg, 38%). LC/MS-ESI observed [M+H]+ 653. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.28 (d, J=6.80 Hz, 6H) 1.37 (s, 9H) 3.08 (d, J=11.33 Hz, 2H) 3.46 (d, J=10.20 Hz, 2H) 3.76 (s, 5H) 4.39 (d, J=6.04 Hz, 2H) 7.41-7.59 (m, 5H) 7.73 (d, J=13.97 Hz, 1H) 7.86 (s, 1H) 8.06 (d, J=2.27 Hz, 1H) 8.42 (s, 1H) 8.50 (d, J=2.27 Hz, 1H) 9.31 (s, 1H)

후처리

  1. temperatureThe mixture was cooled to room temperature
  2. customThe layers were separated
  3. extractionThe aqueous layer was extracted three times with DCM
  4. dry with materialThe combined organics were dried over MgSO4
  5. filtrationThe solution was filtered
  6. concentrationConcentrated in vacuo
  7. customThe crude material was purified by flash chromatography (silica gel, 12 g, 0% to 50% (60:10:1 DCM:MeOH:NH4OH)/DCM gradient)
  8. customto give a cream solid
  9. customThe solid was triturated with Et2O
  10. filtrationThe solid was filtered
  11. dissolutiondissolved in 2 ml DCM
  12. additionA solution of 1.0 M HCl in Et2O (2 ml) was added
  13. customA solid formed
  14. filtrationThe solid was filtered
  15. customdried under vacuum

출처 및 근거

ORD 기록
ord-f1d6daab0fc1409781050ed35743310a
출처 데이터셋
uspto-grants-2015_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08940741B2

반응 노트

불러오는 중…

이 페이지에서참가 물질반응 조건실험 절차후처리출처 및 근거반응 노트