Cesium carbonate → 2-chloro-11-fluoro-6-phenyl-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indole

HRID 1776821Notes

Reaction equation

HRID 1776821 reaction equation
Br[C:2]1[C:3](Br)=[C:4]([CH3:8])[CH:5]=[CH:6][CH:7]=1.[Cl:10][C:11]1[N:16]=[C:15]([C:17]2[NH:18][C:19]3[C:24]([CH:25]=2)=[C:23]([F:26])[CH:22]=[CH:21][CH:20]=3)[C:14]([OH:27])=[CH:13][CH:12]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[Cl:10][C:11]1[CH:12]=[CH:13][C:14]2[O:27][CH:8]([C:4]3[CH:5]=[CH:6][CH:7]=[CH:2][CH:3]=3)[N:18]3[C:19]4[CH:20]=[CH:21][CH:22]=[C:23]([F:26])[C:24]=4[CH:25]=[C:17]3[C:15]=2[N:16]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 346801,2-Dibromo-3-methylbenzeneHCID 867262926-chloro-2-(4-fluoro-1H-indol-2-yl)pyridin-3-ol

Product 1

HCID 867282362-chloro-11-fluoro-6-phenyl-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indoleYield 70%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of dibromotoluene (382 mg, 1.527 mmol, prepared using similar method described for Example 1) in DMF (2 mL) was added slowly to a mixture of compound 6-chloro-2-(4-fluoro-1H-indol-2-yl)pyridin-3-ol (200 mg, 0.763 mmol) and Cs2CO3 (746 mg, 2.289 mmol) in DMF (10 mL) at 100° C. After 10 min, the mixture was concentrated in vacuo. The resulting residue was diluted with water (50 mL) and extracted with ethyl acetate (25 mL×3). The organic layer was washed with brine (50 mL), dried over Na2SO4 and concentrated in vacuo. The resulting residue was purified using column chromatography (petroleum ether:ethyl acetate=50:1) to provide 2-chloro-11-fluoro-6-phenyl-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole (187 mg, yield: 70.0%). 1H-NMR (CDCl3, 400 MHz) δ 7.43 (s, 1H), 7.23˜7.35 (m, 3H), 7.18 (s, 1H), 7.10 (s, 1H), 7.03˜7.08 (m, 4H), 6.79 (m, 1H), 6.65 (d, J=8.4 Hz, 1H). MS (M+H)+: 351/353.

Workup

  1. concentrationthe mixture was concentrated in vacuo
  2. additionThe resulting residue was diluted with water (50 mL)
  3. extractionextracted with ethyl acetate (25 mL×3)
  4. washThe organic layer was washed with brine (50 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified

Sources & evidence

ORD record
ord-c6924aea936a4da8b7f0a0b00ae12660
Source dataset
uspto-grants-2016_02
Patent number
US09265773B2

Reaction notes

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