Hydrochloric Acid → 2-(4-fluorophenyl)-N-methyl-5-(12-methylindolo[1,2-h][1,7]naphthyridin-2-yl)-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

HRID 595753노트

반응식

HRID 595753 반응식
C(O/C=[CH:5]/[C:6]1[C:7]([C:38]2[N:39]([C:48](OC(C)(C)C)=O)[C:40]3[C:45]([C:46]=2[CH3:47])=[CH:44][CH:43]=[CH:42][CH:41]=3)=[N:8][C:9]([C:12]2[C:13]([N:32]([CH3:37])[S:33]([CH3:36])(=[O:35])=[O:34])=[CH:14][C:15]3[O:19][C:18]([C:20]4[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=4)=[C:17]([C:27](=[O:30])[NH:28][CH3:29])[C:16]=3[CH:31]=2)=[CH:10][CH:11]=1)C.Cl>O1CCOCC1>[F:26][C:23]1[CH:22]=[CH:21][C:20]([C:18]2[O:19][C:15]3[CH:14]=[C:13]([N:32]([CH3:37])[S:33]([CH3:36])(=[O:34])=[O:35])[C:12]([C:9]4[CH:10]=[CH:11][C:6]5[CH:5]=[CH:48][N:39]6[C:40]7[CH:41]=[CH:42][CH:43]=[CH:44][C:45]=7[C:46]([CH3:47])=[C:38]6[C:7]=5[N:8]=4)=[CH:31][C:16]=3[C:17]=2[C:27]([NH:28][CH3:29])=[O:30])=[CH:25][CH:24]=1

참가 물질

4

반응물 2

HCID 313Hydrochloric AcidHCID 90333599(E)-tert-butyl 2-(3-(2-ethoxyvinyl)-6-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)pyridin-2-yl)-3-methyl-1H-indole-1-carboxylate

생성물 1

HCID 903410322-(4-fluorophenyl)-N-methyl-5-(12-methylindolo[1,2-h][1,7]naphthyridin-2-yl)-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

시약·촉매·용매 1

HCID 312751,4-Dioxane용매2회

실험 절차

To a solution of (E)-tert-butyl 2-(3-(2-ethoxyvinyl)-6-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)pyridin-2-yl)-3-methyl-1H-indole-1-carboxylate (60 mg, 0.080 mmol) in 1,4-Dioxane (2 mL) was added 4 M HCl in dioxane (1 mL, 4.00 mmol). The resultant bright orange mixture was stirred at ambient temperature for 45 minutes then was heated at 60° C. for 1.75 h. The mixture was concentrated in vacuo, azeotroping from CH3CN, and the residue was diluted with saturated NaHCO3 (aq) solution and extracted into EtOAc. The organic layer was washed with brine (1×), dried over MgSO4, concentrated in vacuo, and purified by silica gel column chromatography using a gradient of 0-70% EtOAc/Hexanes as eluent. Lyophilization from CH3CN/H2O provided the title compound. 1H NMR δ (ppm) (CHCl3-d): 8.27 (1H, s), 8.14 (1H, d, J=7.34 Hz), 8.09˜8.05 (2H, m), 7.91˜7.84 (3H, m), 7.71˜7.68 (2H, m), 7.46˜7.43 (2H, m), 7.24 (2H, t, J=8.65 Hz), 6.61 (1H, d, J=7.33 Hz), 5.96 (1H, br s), 3.35 (3H, s), 3.06 (6H, m), 2.73 (3H, s). MS (M+H): 607.

후처리

  1. temperaturethen was heated at 60° C. for 1.75 h
  2. concentrationThe mixture was concentrated in vacuo
  3. customazeotroping from CH3CN
  4. additionthe residue was diluted with saturated NaHCO3 (aq) solution
  5. extractionextracted into EtOAc
  6. washThe organic layer was washed with brine (1×)
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated in vacuo
  9. custompurified by silica gel column chromatography

출처 및 근거

ORD 기록
ord-4d2450c3c16c4e798e54e35f7ebce14f
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09243002B2

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