Lithium Hydroxide → 6-Tert-butyl-8-fluoro-2-[4-[5-[[5-(3-hydroxyazetidin-1-yl)-2-pyridyl]amino]-1-methyl-6-oxo-3-pyridyl]-3-(hydroxymethyl)-2-pyridyl]phthalazin-1-one

HRID 407773노트

반응식

HRID 407773 반응식
C([O:4][CH2:5][C:6]1[C:7]([N:32]2[N:41]=[CH:40][C:39]3[C:34](=[C:35]([F:46])[CH:36]=[C:37]([C:42]([CH3:45])([CH3:44])[CH3:43])[CH:38]=3)[C:33]2=[O:47])=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[C:16]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([N:25]3[CH2:28][CH:27]([OH:29])[CH2:26]3)=[CH:21][N:20]=2)[C:15](=[O:30])[N:14]([CH3:31])[CH:13]=1)(=O)C.[OH-].[Li+]>C(O)(C)C.C1COCC1.O>[C:42]([C:37]1[CH:38]=[C:39]2[C:34](=[C:35]([F:46])[CH:36]=1)[C:33](=[O:47])[N:32]([C:7]1[C:6]([CH2:5][OH:4])=[C:11]([C:12]3[CH:17]=[C:16]([NH:18][C:19]4[CH:24]=[CH:23][C:22]([N:25]5[CH2:28][CH:27]([OH:29])[CH2:26]5)=[CH:21][N:20]=4)[C:15](=[O:30])[N:14]([CH3:31])[CH:13]=3)[CH:10]=[CH:9][N:8]=1)[N:41]=[CH:40]2)([CH3:45])([CH3:43])[CH3:44]

참가 물질

4

반응물 2

HCID 3939Lithium HydroxideHCID 86684036(2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(5-(5-(3-hydroxyazetidin-1-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)pyridin-3-yl)methyl Acetate

생성물 1

HCID 866840376-Tert-butyl-8-fluoro-2-[4-[5-[[5-(3-hydroxyazetidin-1-yl)-2-pyridyl]amino]-1-methyl-6-oxo-3-pyridyl]-3-(hydroxymethyl)-2-pyridyl]phthalazin-1-one수율 31%

시약·촉매·용매 1

HCID 22722550Tetrahydrofuran water isopropanol용매

실험 절차

A mixture of 147d (140 mg, 0.22 mmol) and lithium hydroxide (132 mg, 5.5 mmol) in i-propanol/THF/water (2:2:1, 10 mL) was stirred at room temperature for 1 hour. The mixture was concentrated under reduced pressure and diluted with water (10 mL). The resulting mixture was extracted with dichloromethane three times. The combined organic layer was concentrated under reduced pressure and the resulting residue was purified by reverse-phase prep-HPLC to afford 147 (40 mg, 31%) as a yellow solid. MS-ESI: [M+H]+ 598.2. 1H NMR (500 MHz, DMSO-d6) δ 8.57-8.53 (m, 3H), 8.32 (s, 1H), 7.90 (s, 1H), 7.77 (d, J=13.0 Hz, 1H), 7.51-7.49 (m, 2H), 7.43 (s, 1H), 7.19 (d, J=8.5 Hz, 1H), 6.88 (dd, J=3.0, 8.5 Hz, 1H), 5.57-5.56 (m, 1H), 4.89-4.87 (m, 1H), 4.55-4.52 (m, 1H), 4.43-4.41 (m, 2H), 4.05-4.02 (m, 2H), 3.60 (s, 3H), 3.45-3.42 (m, 2H), 1.39 (s, 9H).

후처리

  1. concentrationThe mixture was concentrated under reduced pressure
  2. additiondiluted with water (10 mL)
  3. extractionThe resulting mixture was extracted with dichloromethane three times
  4. concentrationThe combined organic layer was concentrated under reduced pressure
  5. customthe resulting residue was purified by reverse-phase prep-HPLC

출처 및 근거

ORD 기록
ord-8f808e3a1d8e4b08ae28b69f90970a4b
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08754077B2

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