Lithium Hydroxide → 3-[3-(Hydroxymethyl)-4-[1-methyl-5-[(5-methylisoxazol-3-yl)amino]-6-oxo-3-pyridyl]-2-pyridyl]-6,7,8,9-tetrahydrobenzothiopheno[2,3-d]pyridazin-4-one

HRID 1412016노트

반응식

HRID 1412016 반응식
C([O:4][CH2:5][C:6]1[C:7]([N:27]2[C:39](=[O:40])[C:38]3[S:37][C:36]4[CH2:35][CH2:34][CH2:33][CH2:32][C:31]=4[C:30]=3[CH:29]=[N:28]2)=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[C:16]([NH:18][C:19]2[CH:23]=[C:22]([CH3:24])[O:21][N:20]=2)[C:15](=[O:25])[N:14]([CH3:26])[CH:13]=1)(=O)C.[OH-].[Li+]>C1COCC1.C(O)(C)C.O>[OH:4][CH2:5][C:6]1[C:7]([N:27]2[C:39](=[O:40])[C:38]3[S:37][C:36]4[CH2:35][CH2:34][CH2:33][CH2:32][C:31]=4[C:30]=3[CH:29]=[N:28]2)=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[C:16]([NH:18][C:19]2[CH:23]=[C:22]([CH3:24])[O:21][N:20]=2)[C:15](=[O:25])[N:14]([CH3:26])[CH:13]=1

참가 물질

4

반응물 2

HCID 3939Lithium HydroxideHCID 86684535(4-{1-Methyl-5-[(5-methyl-1,2-oxazol-3-yl)amino]-6-oxo-1,6-dihydropyridin-3-yl}-2-{6-oxo-8-thia-4,5-diazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3-trien-5-yl}pyridin-3-yl)methyl Acetate

생성물 1

HCID 866845373-[3-(Hydroxymethyl)-4-[1-methyl-5-[(5-methylisoxazol-3-yl)amino]-6-oxo-3-pyridyl]-2-pyridyl]-6,7,8,9-tetrahydrobenzothiopheno[2,3-d]pyridazin-4-one수율 60.2%

시약·촉매·용매 1

HCID 22722550Tetrahydrofuran water isopropanol용매

실험 절차

To a solution of 291a (100 mg, 0.18 mmol) in THF/i-propanol/water (10/5/5 mL) was added lithium hydroxide (43 mg, 1.8 mmol) at room temperature. After being stirred for 1 h, MS indicated the reaction was complete. Then the mixture was concentrated under reduced pressure and the residue was partitioned between water (10 mL) and dichloromethane (15 mL). The water phase was extracted with dichloromethane (3×10 mL). The combined organic layer was washed with brine (30 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by reverse-phase prep-HPLC to afford 291 (56 mg, 60%) as white solid. MS-ESI: [M+H]+ 517.2. 1H NMR (500 MHz, DMSO-d6) δ 9.02 (s, 1H), 8.58 (d, J=5.0 Hz, 1H), 8.48 (s, 1H), 8.00 (d, J=2.0 Hz, 1H), 7.58 (d, J=2.0 Hz, 1H), 7.52 (d, J=5.0 Hz, 1H), 6.25 (s, 1H), 4.87-4.85 (m, 1H), 4.42-4.36 (m, 2H), 3.61 (s, 3H), 2.98-2.85 (m, 4H), 2.32 (s, 3H), 1.92-1.86 (m, 4H).

후처리

  1. concentrationThen the mixture was concentrated under reduced pressure
  2. customthe residue was partitioned between water (10 mL) and dichloromethane (15 mL)
  3. extractionThe water phase was extracted with dichloromethane (3×10 mL)
  4. washThe combined organic layer was washed with brine (30 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by reverse-phase prep-HPLC

출처 및 근거

ORD 기록
ord-75efd78a306f4e6590872c247a477571
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08921353B2

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