Lithium hydroxide, monohydrate → 2-(((11-fluoro-2-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-6-yl)methyl)amino)acetic acid

HRID 1776866Notes

Reaction equation

HRID 1776866 reaction equation
[F:1][C:2]1[C:3]2[CH:4]=[C:5]3[C:14]4[N:15]=[C:16]([C:19]5[C:20]([N:39]([CH3:44])[S:40]([CH3:43])(=[O:42])=[O:41])=[CH:21][C:22]6[O:26][C:25]([C:27]7[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=7)=[C:24]([C:34](=[O:37])[NH:35][CH3:36])[C:23]=6[CH:38]=5)[CH:17]=[CH:18][C:13]=4[O:12][CH:11]([CH2:45][NH:46][CH2:47][C:48]([O:50]CC)=[O:49])[N:6]3[C:7]=2[CH:8]=[CH:9][CH:10]=1.O[Li].O>O1CCOCC1.O>[F:1][C:2]1[C:3]2[CH:4]=[C:5]3[C:14]4[N:15]=[C:16]([C:19]5[C:20]([N:39]([CH3:44])[S:40]([CH3:43])(=[O:42])=[O:41])=[CH:21][C:22]6[O:26][C:25]([C:27]7[CH:28]=[CH:29][C:30]([F:33])=[CH:31][CH:32]=7)=[C:24]([C:34](=[O:37])[NH:35][CH3:36])[C:23]=6[CH:38]=5)[CH:17]=[CH:18][C:13]=4[O:12][CH:11]([CH2:45][NH:46][CH2:47][C:48]([OH:50])=[O:49])[N:6]3[C:7]=2[CH:8]=[CH:9][CH:10]=1

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 86728268ethyl 2-(((11-fluoro-2-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-6-yl)methyl)amino)acetate

Product 1

HCID 867282702-(((11-fluoro-2-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-6-yl)methyl)amino)acetic acidYield 91%

Reagents, catalysts & solvents 1

HCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

To a solution of ethyl 2-(((11-fluoro-2-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-6-yl)methyl)amino)acetate (35 mg, 0.048 mmol) in 1,4-dioxane/H2O (3.0 mL/0.5 mL) was added LiOH.H2O (20 mg, 0.45 mmol). The mixture was stirred at room temperature overnight. Then it was concentrated in vacuo, neutralized with HCl (aq. 5%), extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4 and concentrated to provide Compound 116 (30 mg, yield: 91%). 1H-NMR (DMSO-d6, 400 MHz) δ 8.58 (d, J=4.8 Hz, 1H), 8.00˜8.07 (m, 2H), 7.85 (s, 1H), 7.69 (d, J=8.8 Hz, 1H), 7.61 (d, J=8.4 Hz, 1H), 7.52 (d, J=8.4 Hz, 1H), 7.43 (t, J=8.8 Hz, 2H), 7.20˜7.29 (m, 1H), 7.09 (s, 1H), 6.89˜6.97 (m, 1H), 6.85 (br. s, 1H), 3.19 (s, 3H), 3.07 (m, 2H), 2.88 (s, 3H), 2.83 (s, 3H). MS (M+H)+: 702.

Workup

  1. concentrationThen it was concentrated in vacuo
  2. extractionextracted with EtOAc
  3. washThe organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-44a6263b38084ff6b4860c36c6290980
Source dataset
uspto-grants-2016_02
Patent number
US09265773B2

Reaction notes

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