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 1412016ノート

反応式

HRID 1412016 の反応式
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

参加物

4

反応物 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

生成物 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-one収率 60.2%

試薬・触媒・溶媒 1

HCID 22722550Tetrahydrofuran water isopropanol溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-75efd78a306f4e6590872c247a477571
出典データセット
uspto-grants-2014_12
特許番号
US08921353B2

反応ノート

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