Sodium Hydroxide → 6-tert-Butyl-8-fluoro-2-{2-hydroxymethyl-3-[1-methyl-5-(1'-methyl-1',2',3',4',5',6'-hexahydro-[3,4]bipyridinyl-6-ylamino)-6-oxo-1,6-dihydro-pyridazin-3-yl]-phenyl}-2H-phthalazin-1-one

HRID 1431201

반응식

HRID 1431201 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]([CH:25]4[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27][CH2:26]4)=[CH:21][N:20]=3)[C:15](=[O:32])[N:14]([CH3:33])[N:13]=2)=[CH:10][CH:9]=[CH:8][C:7]=1[N:34]1[N:43]=[CH:42][C:41]2[C:36](=[C:37]([F:48])[CH:38]=[C:39]([C:44]([CH3:47])([CH3:46])[CH3:45])[CH:40]=2)[C:35]1=[O:49])(=O)C.[OH-].[Na+]>C1COCC1>[C:44]([C:39]1[CH:40]=[C:41]2[C:36](=[C:37]([F:48])[CH:38]=1)[C:35](=[O:49])[N:34]([C:7]1[CH:8]=[CH:9][CH:10]=[C:11]([C:12]3[CH:17]=[C:16]([NH:18][C:19]4[N:20]=[CH:21][C:22]([CH:25]5[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27][CH2:26]5)=[CH:23][CH:24]=4)[C:15](=[O:32])[N:14]([CH3:33])[N:13]=3)[C:6]=1[CH2:5][OH:4])[N:43]=[CH:42]2)([CH3:47])([CH3:45])[CH3:46]

참가 물질

4

반응물 2

HCID 14798Sodium Hydroxide2회HCID 667426042-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(1-methyl-5-(5-(1-methylpiperidin-4-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridazin-3-yl)benzyl acetate

생성물 1

HCID 566564516-tert-Butyl-8-fluoro-2-{2-hydroxymethyl-3-[1-methyl-5-(1'-methyl-1',2',3',4',5',6'-hexahydro-[3,4]bipyridinyl-6-ylamino)-6-oxo-1,6-dihydro-pyridazin-3-yl]-phenyl}-2H-phthalazin-1-one수율 84.7%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(1-methyl-5-(5-(1-methylpiperidin-4-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridazin-3-yl)benzyl acetate (1.6 g) was dissolved in 20 mL THF. To the reaction solution was added 12 mL of 2 N NaOH. The reaction mixture was stirred at room temperature overnight. Reaction was not complete. An additional 10 equiv. of 2 N NaOH was added and the reaction mixture was stirred at room temperature for an additional 2 hours. THF was added until the reaction mixture was homogeneous and the reaction was heated to 40° C. for 30 min. The reaction was allowed to cool to room temperature and stirred overnight. The reaction had gone to completion as indicated by LC/MS. The reaction was concentrated to a reduced volume to remove most of the THF. A solid formed which was collected by filtration. The solid was redissolved in DCM, filtered through pack of celite, washed with water, dried over Na2SO4, filtered and conc in vacuo. to afford the desired product as a white solid (1.27 g). (M+H)+=624 m/e. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.45 (s, 9H) 1.80-1.92 (m, 5H) 2.31-2.58 (m, 3H) 3.03 (d, J=8.28 Hz, 1H) 3.92 (s and overlapping multiplet, 4H) 4.45 (d, J=6.53 Hz, 2H) 6.93 (d, J=8.28 Hz, 1H) 7.45-7.63 (m, 5H) 7.65-7.71 (m, 1H) 8.22-8.32 (m, 3H) 8.61 (s, 1H).

후처리

  1. customReaction
  2. stirringthe reaction mixture was stirred at room temperature for an additional 2 hours
  3. temperaturethe reaction was heated to 40° C. for 30 min
  4. temperatureto cool to room temperature
  5. stirringstirred overnight
  6. concentrationThe reaction was concentrated to a reduced volume
  7. customto remove most of the THF
  8. customA solid formed which
  9. filtrationwas collected by filtration
  10. dissolutionThe solid was redissolved in DCM
  11. filtrationfiltered through pack of celite
  12. washwashed with water
  13. dry with materialdried over Na2SO4
  14. filtrationfiltered and conc in vacuo

출처 및 근거

ORD 기록
ord-a841eccbb33d406991df4c1b2a818d46
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08940741B2

연결된 노트

불러오는 중…