Hydrochloric Acid → HCID 86728249, compound

HRID 1776842Notes

Reaction equation

HRID 1776842 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:20]=[C:19]([N:21]([CH3:26])[S:22]([CH3:25])(=[O:24])=[O:23])[C:18]([C:27]4[CH:28]=[CH:29][C:30]5[O:46][CH2:45][N:33]6[C:34]7[CH:35]=[CH:36][CH:37]=[C:38]([C:41]([O:43]C)=[O:42])[C:39]=7[CH:40]=[C:32]6[C:31]=5[N:47]=4)=[CH:17][C:11]=3[C:12]=2[C:13](=[O:16])[NH:14][CH3:15])=[CH:4][CH:3]=1.O[Li].O.Cl>O1CCOCC1.O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[O:9][C:10]3[CH:20]=[C:19]([N:21]([CH3:26])[S:22]([CH3:25])(=[O:24])=[O:23])[C:18]([C:27]4[CH:28]=[CH:29][C:30]5[O:46][CH2:45][N:33]6[C:34]7[CH:35]=[CH:36][CH:37]=[C:38]([C:41]([OH:43])=[O:42])[C:39]=7[CH:40]=[C:32]6[C:31]=5[N:47]=4)=[CH:17][C:11]=3[C:12]=2[C:13](=[O:16])[NH:14][CH3:15])=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 86728247HCID 86728247, compound

Product 1

HCID 86728249HCID 86728249, compoundYield 78%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of methyl 2-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole-11-carboxylate (160 mg, 0.24 mmol) in dioxane (2 mL) and water (2 mL), LiOH.H2O (30 mg, 0.71 mmol) was added and the mixture was heated to reflux for 2 hours. Then removed dioxane and the mixture was diluted with water, adjusted to pH=3˜4 by 1 N HCl, and extracted with EtOAc. The combined organic phases were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The resulting residue was purified using PTLC (dichloromethane:MeOH=20:1) to provide 2-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole-11-carboxylic acid (120 mg, yield: 76%). 1H-NMR (Methanol-d4, 400 MHz) δ 7.97˜8.02 (m, 2H), 7.86˜7.91 (m, 3H), 7.81 (s, 1H), 7.74 (d, J=8.4 Hz, 1H), 7.59 (s, 2H), 7.31˜7.36 (m, 1H), 7.24˜7.29 (m, 2H), 6.14 (s, 2H), 3.35 (s, 3H), 2.96 (s, 3H), 2.88 (s, 3H). MS (M+H)+: 641.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 2 hours
  3. extractionextracted with EtOAc
  4. washThe combined organic phases were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe resulting residue was purified

Sources & evidence

ORD record
ord-5e22c241fae847829aba04e3359fbeb7
Source dataset
uspto-grants-2016_02
Patent number
US09265773B2

Reaction notes

Loading…