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Water → 6-tert-butyl-2-[4-[5-(5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-2-ylamino)-1-methyl-6-oxo-3-pyridyl]-3-(hydroxymethyl)-2-pyridyl]-8-fluoro-phthalazin-1-one

HRID 1185244
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HRID 1185244 반응식
C([O:4][CH2:5][C:6]1[C:7]([N:29]2[N:38]=[CH:37][C:36]3[C:31](=[C:32]([F:43])[CH:33]=[C:34]([C:39]([CH3:42])([CH3:41])[CH3:40])[CH:35]=3)[C:30]2=[O:44])=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[C:16]([NH:18][C:19]2[CH:20]=[C:21]3[CH2:26][CH2:25][CH2:24][N:22]3[N:23]=2)[C:15](=[O:27])[N:14]([CH3:28])[CH:13]=1)(=O)C.[OH-].[Li+].O>C1COCC1.C(O)(C)C.O>[C:39]([C:34]1[CH:35]=[C:36]2[C:31](=[C:32]([F:43])[CH:33]=1)[C:30](=[O:44])[N:29]([C:7]1[C:6]([CH2:5][OH:4])=[C:11]([C:12]3[CH:17]=[C:16]([NH:18][C:19]4[CH:20]=[C:21]5[CH2:26][CH2:25][CH2:24][N:22]5[N:23]=4)[C:15](=[O:27])[N:14]([CH3:28])[CH:13]=3)[CH:10]=[CH:9][N:8]=1)[N:38]=[CH:37]2)([CH3:42])([CH3:40])[CH3:41]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

5

반응물 3

HCID 962WaterHCID 3939Lithium HydroxideHCID 86684090(2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(5-(5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)pyridin-3-yl)methyl Acetate

생성물 1

HCID 866840916-tert-butyl-2-[4-[5-(5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-2-ylamino)-1-methyl-6-oxo-3-pyridyl]-3-(hydroxymethyl)-2-pyridyl]-8-fluoro-phthalazin-1-one수율 33.7%

시약·촉매·용매

1
HCID 22722550Tetrahydrofuran water isopropanol용매

실험 절차

To a solution of 162d (50 mg, 0.080 mmol) in THF/i-propanol/water (1/1/0.5 ml) was added lithium hydroxide (19 mg, 0.80 mmol) at room temperature. After the reaction was stirred for 2.5 h, LCMS indicated the reaction was complete. Then the mixture was poured into water (15 mL) and extracted with dichloromethane (3×20 mL). The combined organic layer was washed with brine (30 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue solid was purified by reverse-phase prep-HPLC (A: 1% NH4HCO3/water, B: acetonitrile) to afford 162 (15 mg, 33.3%) as white solid. MS-ESI: [M+H]+ 556.3. 1H NMR (500 MHz, CDCl3) δ 8.62 (d, J=5.0 Hz, 1H), 8.32 (s, 1H), 7.93 (d, J=2.0 Hz, 1H), 7.55-7.47 (m, 4H), 7.26 (s, 1H), 5.74 (s, 1H), 4.47 (d, J=4.0 Hz, 2H), 4.07 (t, J=2.0 Hz, 2H), 3.70 (s, 3H), 2.87 (t, J=6.5 Hz, 2H), 2.55-2.52 (m, 2H), 1.45 (s, 9H).

후처리

  1. extractionextracted with dichloromethane (3×20 mL)
  2. washThe combined organic layer was washed with brine (30 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue solid was purified by reverse-phase prep-HPLC (A: 1% NH4HCO3/water, B

출처 및 근거

ORD 기록
ord-bbe6aa8fc5094f3fb49039c3a5b92895
출처 데이터셋
uspto-grants-2014_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08669251B2

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