Triethylamine → 5-(11-fluoro-6-(methylsulfonamidomethyl)-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

HRID 1776871Notes

Reaction equation

HRID 1776871 reaction equation
[NH2:1][CH2:2][CH:3]1[N:8]2[C:9]3[CH:10]=[CH:11][CH:12]=[C:13]([F:16])[C:14]=3[CH:15]=[C:7]2[C:6]2[N:17]=[C:18]([C:21]3[C:22]([N:41]([CH3:46])[S:42]([CH3:45])(=[O:44])=[O:43])=[CH:23][C:24]4[O:28][C:27]([C:29]5[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=5)=[C:26]([C:36]([NH:38][CH3:39])=[O:37])[C:25]=4[CH:40]=3)[CH:19]=[CH:20][C:5]=2[O:4]1.CCN(CC)CC.[CH3:54][S:55](Cl)(=[O:57])=[O:56]>ClCCl.O>[F:16][C:13]1[C:14]2[CH:15]=[C:7]3[C:6]4[N:17]=[C:18]([C:21]5[C:22]([N:41]([CH3:46])[S:42]([CH3:45])(=[O:43])=[O:44])=[CH:23][C:24]6[O:28][C:27]([C:29]7[CH:30]=[CH:31][C:32]([F:35])=[CH:33][CH:34]=7)=[C:26]([C:36]([NH:38][CH3:39])=[O:37])[C:25]=6[CH:40]=5)[CH:19]=[CH:20][C:5]=4[O:4][CH:3]([CH2:2][NH:1][S:55]([CH3:54])(=[O:57])=[O:56])[N:8]3[C:9]=2[CH:10]=[CH:11][CH:12]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 867282695-(6-(aminomethyl)-11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

Product 1

HCID 867282745-(11-fluoro-6-(methylsulfonamidomethyl)-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamideYield 35.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 5-(6-(aminomethyl)-11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (50 mg, 0.08 mmol), and Et3N (11 mg, 0.12 mmol) in dichloromethane (1 mL) was stirred at room temperature under N2 protection. Then MsCl (11 mg, 0.09 mmol) was added and the solution was stirred at room temperature for overnight. Then the mixture was diluted with water (50 mL) and extracted with EtOAc (10 mL*3). The combined organic layer was washed with brine (30 mL), dried over Na2SO4 and concentrated in vacuo. The resulting residue was purified using prep-TLC (dichloromethane:MeOH=15:1) to provide 5-(11-fluoro-6-(methylsulfonamidomethyl)-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (20 mg, yield: 35.7%). 1H-NMR (400 MHz, DMSO-d6) δ 8.55 (d, J=4.8 Hz, 1H), 7.83 (s, 1H), 7.96˜8.06 (m, 3H), 7.65˜7.70 (m, 1H), 7.59˜7.63 (m, 1H), 7.57 (t, J=6.4 Hz, 1H), 7.37˜7.44 (m, 3H), 7.24˜7.30 (m, 1H), 7.10 (s, 1H), 6.91˜6.97 (m, 1H), 6.77 (dd, J=6.8 Hz, 4.4 Hz, 1H), 3.37 (dd, J=14.0, 7.2 Hz, 2H), 3.29 (br s, 3H), 2.89 (s, 3H), 2.77˜2.87 (m, 6H). MS (M+H)+: 722.

Workup

  1. stirringthe solution was stirred at room temperature for overnight
  2. extractionextracted with EtOAc (10 mL*3)
  3. washThe combined organic layer was washed with brine (30 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified

Sources & evidence

ORD record
ord-0ce95133af83405692a56f49d4acf9c3
Source dataset
uspto-grants-2016_02
Patent number
US09265773B2

Reaction notes

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