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

HRID 1776944Notes

Reaction equation

HRID 1776944 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[NH:9][C:10]3[C:15]([CH:16]=2)=[C:14]([F:17])[CH:13]=[CH:12][CH:11]=3)[C:5]([OH:18])=[CH:4][CH:3]=1.[C:19]([O-])([O-])=O.[Cs+].[Cs+].ClCI>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:18][CH2:19][N:9]3[C:10]4[CH:11]=[CH:12][CH:13]=[C:14]([F:17])[C:15]=4[CH:16]=[C:8]3[C:6]=2[N:7]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 11644ChloroiodomethaneHCID 867262926-chloro-2-(4-fluoro-1H-indol-2-yl)pyridin-3-ol

Product 1

HCID 867283052-chloro-11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indoleYield 86.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 6-chloro-2-(4-fluoro-1H-indol-2-yl)pyridin-3-ol (2 g, 7.6 mmol) and Cs2CO3 (7.46 g, 22.89 mmol) in DMF (100 mL) was stirred at 100° C. (internal temperature) for 15 min, and then chloroiodomethane (2.85 g, 15.3 mmol) in DMF (2 mL) was added dropwise. After the reaction was completed, the mixture was filtered and concentrated in vacuo. The resulting residue was diluted with water (50 mL) and extracted with ethyl acetate (30 mL×3). The organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuo. The resulting residue was purified using column chromatography (petroleum ether:EA=10:1) to provide 2-chloro-11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole (1.8 g, yield: 86.1%). 1H-NMR (DMSO-d6, 400 MHz) δ 7.64 (d, J=8.8 Hz, 1H), 7.39˜7.46 (m, 2H), 7.21˜7.25 (m, 1H), 7.06 (s, 1H), 6.88˜6.92 (m, 1H), 6.18 (s, 2H). MS (M+H)+: 275/277.

Workup

  1. filtrationthe mixture was filtered
  2. concentrationconcentrated in vacuo
  3. additionThe resulting residue was diluted with water (50 mL)
  4. extractionextracted with ethyl acetate (30 mL×3)
  5. washThe organic layer was washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe resulting residue was purified

Sources & evidence

ORD record
ord-ac32f0e767cc456d8521d8edb8581b96
Source dataset
uspto-grants-2016_02
Patent number
US09265773B2

Reaction notes

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