Lithium hydroxide, monohydrate → N-[2-[[6-[[5-[5-fluoro-2-(hydroxymethyl)-3-(4-oxo-6,7,8,9-tetrahydrobenzothiopheno[2,3-d]pyridazin-3-yl)phenyl]-1-methyl-2-oxo-3-pyridyl]amino]-2-pyridyl]amino]ethyl]prop-2-enamide

HRID 1774639ノート

反応式

HRID 1774639 の反応式
[F:1][C:2]1[CH:3]=[C:4]([N:36]2[C:41](=[O:42])[C:40]3[S:43][C:44]4[CH2:49][CH2:48][CH2:47][CH2:46][C:45]=4[C:39]=3[CH:38]=[N:37]2)[C:5]([CH2:31][O:32]C(=O)C)=[C:6]([C:8]2[CH:9]=[C:10]([NH:16][C:17]3[N:22]=[C:21]([NH:23][CH2:24][CH2:25][NH:26][C:27](=[O:30])[CH:28]=[CH2:29])[CH:20]=[CH:19][CH:18]=3)[C:11](=[O:15])[N:12]([CH3:14])[CH:13]=2)[CH:7]=1.O[Li].O>C1COCC1.CC(O)C.O>[F:1][C:2]1[CH:3]=[C:4]([N:36]2[C:41](=[O:42])[C:40]3[S:43][C:44]4[CH2:49][CH2:48][CH2:47][CH2:46][C:45]=4[C:39]=3[CH:38]=[N:37]2)[C:5]([CH2:31][OH:32])=[C:6]([C:8]2[CH:9]=[C:10]([NH:16][C:17]3[N:22]=[C:21]([NH:23][CH2:24][CH2:25][NH:26][C:27](=[O:30])[CH:28]=[CH2:29])[CH:20]=[CH:19][CH:18]=3)[C:11](=[O:15])[N:12]([CH3:14])[CH:13]=2)[CH:7]=1

参加物

6

反応物 2

HCID 168937Lithium hydroxide, monohydrateHCID 118116546N-[2-[[6-[[5-[5-fluoro-2-(acetoxymethyl)-3-(4-oxo-6,7,8,9-tetrahydrobenzothiopheno[2,3-d]pyridazin-3-yl)phenyl]-1-methyl-2-oxo-3-pyridyl]amino]-2-pyridyl]amino]ethyl]prop-2-enamide

生成物 1

HCID 118116397N-[2-[[6-[[5-[5-fluoro-2-(hydroxymethyl)-3-(4-oxo-6,7,8,9-tetrahydrobenzothiopheno[2,3-d]pyridazin-3-yl)phenyl]-1-methyl-2-oxo-3-pyridyl]amino]-2-pyridyl]amino]ethyl]prop-2-enamide収率 62.2%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 3776Isopropanol溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a mixture of 105f (125 mg, 0.183 mmol) in THF (6 mL), i-PrOH (2 mL) and H2O (2 mL) was added LiOH.H2O (37 mg, 0.915 mmol). The reaction mixture was stirred at rt for 16 h and concentrated. The residue was partitioned between water and DCM. The organic layer was separated, dried over Na2SO4, filtered and concentrated. The residue was washed with EA and dried to give 105 (73 mg, 60%) as gray solid. 1H NMR (500 MHz, DMSO-d6): δ 8.56 (s, 1H), 8.48 (s, 1H),), 8.20 (s, 1H), 8.12 (s, 1H), 7.42 (s, 1H), 7.38-7.32 (m, 2H), 7.23 (t, J=8.0 Hz, 1H), 6.52 (s, 1H), 6.35 (d, J=8.0 Hz, 1H), 6.21-6.15 (m, 1H), 6.05-6.02 (m, 1H), 5.95 (d, J=8.0 Hz, 1H), 4.73 (s, 1H), 4.33 (s, 2H), 3.59 (s, 3H), 3.28-3.25 (m, 5H), 2.93 (bs, 2H), 2.84 (bs, 2H), 1.88 (bs, 4H). ESI-LCMS: m/z=642 [C34H34FN7O5+H]+

後処理

  1. concentrationconcentrated
  2. customThe residue was partitioned between water and DCM
  3. customThe organic layer was separated
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. washThe residue was washed with EA
  8. customdried

出典と根拠

ORDレコード
ord-20fc601f29bc427d9c0aba2fef5ec13a
出典データセット
uspto-grants-2016_02
特許番号
US09260415B2

反応ノート

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