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 595753Notes

Reaction equation

HRID 595753 reaction equation
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

Participants

4

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-4d2450c3c16c4e798e54e35f7ebce14f
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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