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 1774639노트

반응식

HRID 1774639 반응식
[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

참가 물질

6

반응물 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

생성물 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-enamide수율 62.2%

시약·촉매·용매 3

HCID 962Water용매HCID 3776Isopropanol용매HCID 8028Tetrahydrofuran용매

실험 절차

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]+

후처리

  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

출처 및 근거

ORD 기록
ord-20fc601f29bc427d9c0aba2fef5ec13a
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09260415B2

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