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

HRID 595711Notes

Reaction equation

HRID 595711 reaction equation
[Cl:1][C:2]1[N:7]=[N:6][C:5]([CH2:8][CH2:9]Cl)=[C:4]([C:11]2[NH:12][C:13]3[C:18]([CH:19]=2)=[C:17]([F:20])[CH:16]=[CH:15][CH:14]=3)[CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[Cl:1][C:2]1[N:7]=[N:6][C:5]2[CH2:8][CH2:9][N:12]3[C:13]4[CH:14]=[CH:15][CH:16]=[C:17]([F:20])[C:18]=4[CH:19]=[C:11]3[C:4]=2[CH:3]=1

Participants

4

Reactant 2

HCID 10796Cesium carbonateHCID 903339492-(6-chloro-3-(2-chloroethyl)pyridazin-4-yl)-4-fluoro-1H-indole

Product 1

HCID 903335802-Chloro-11-fluoro-5,6-dihydropyridazino[4',3':3,4]pyrido[1,2-a]indoleYield 86%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a suspension of 2-(6-chloro-3-(2-chloroethyl)pyridazin-4-yl)-4-fluoro-1H-indole (60 mg, 0.17 mmol) in DMF (1 mL) was added Cs2CO3 (124 mg, 0.34 mmol), and then the mixture was stirred for 20 minutes at 60° C. After being concentrated in vacuo, the resulting residue was suspended in H2O and extracted with DCM. The combined organic layer was washed with H2O and dried over Na2SO4. After concentration, the residue was purified by prep-TLC (DCM) to give the product of 2-chloro-11-fluoro-5,6-dihydropyridazino[4′,3′:3,4]pyrido[1,2-a]indole (40 mg, yield: 75%). 1H-NMR (CDCl3, 400 MHz) δ 8.40 (s, 1H), 7.63 (s, 1H), 7.47 (d, J=8.22 Hz, 1H), 7.24˜7.33 (m, 1H), 6.87˜6.97 (m, 1H), 4.52 (t, J=6.4 Hz, 2H), 3.53 (t, J=6.4 Hz, 2H). MS (M+H)+: 274/276.

Workup

  1. concentrationAfter being concentrated in vacuo
  2. extractionextracted with DCM
  3. washThe combined organic layer was washed with H2O
  4. dry with materialdried over Na2SO4
  5. concentrationAfter concentration
  6. customthe residue was purified by prep-TLC (DCM)

Sources & evidence

ORD record
ord-07815ec232ba4908a69a799cfa11b673
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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