Water → HCID 57876000, compound

HRID 2195913Notes

Reaction equation

HRID 2195913 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:12]=[CH:11][C:10]2[NH:9][C:8]3[CH2:13][CH2:14][N:15]([CH3:17])[CH2:16][C:7]=3[C:6]=2[CH:5]=1.Br[CH2:19][CH2:20][CH2:21][C:22]1[CH:23]=[CH:24][C:25]([C:28]([F:31])([F:30])[F:29])=[N:26][CH:27]=1.O>CN(C=O)C>[Cl:3][C:4]1[CH:12]=[CH:11][C:10]2[N:9]([CH2:19][CH2:20][CH2:21][C:22]3[CH:27]=[N:26][C:25]([C:28]([F:31])([F:29])[F:30])=[CH:24][CH:23]=3)[C:8]3[CH2:13][CH2:14][N:15]([CH3:17])[CH2:16][C:7]=3[C:6]=2[CH:5]=1

Participants

6

Reactant 4

HCID 962WaterHCID 196158-chloro-2-methyl-1H,2H,3H,4H,5H-pyrido(4,3-b)indoleHCID 24758Sodium hydrideHCID 668695135-(3-Bromopropyl)-2-(trifluoromethyl)pyridine

Product 1

HCID 57876000HCID 57876000, compoundYield 32.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of sodium hydride (0.014 g, 0.00054 mol) in dry DMF (3 mL), 8-Chloro-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (0.1 g, 0.00045 mol) was added at ice cold temp and stirred for 2 h at room temperature. Reaction mix was cooled to −20° C. and 5-(3-Bromo-propyl)-2-trifluoromethyl-pyridine (0.183 g, 0.00068 mol) was added, stirred for 1 h at 15° C. Reaction was monitor by TLC. After completion (TLC), reaction mix was cooled to 0° C. and water (10 mL) was added, extracted with ethyl acetate (3×100 mL). The organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure using rotary evaporator. The crude was purified through column chromatography (4% Methanol:DCM in silica 100-200 mesh, Diameter of column—2.5 cm, Height of silica—approx. 5 inch) to provide desired compound as brown oil (0.06 g, 32% yield). 8-Chloro-2-methyl-5-[3-(6-trifluoromethyl-pyridin-3-yl)-propyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (0.06 g, 0.000147 mol) was dissolved in THF (1.0 mL), A solution of oxalic acid dihydrate (0.016 g, 0.000126 mol) in THF (1.0 mL) was added and stirred for 30 min at RT. The precipitate was filtered and dried to give oxalate salt as off white solid (0.050 g, 68% yield).

Workup

  1. additionwas added at ice cold temp
  2. customReaction
  3. additionmix
  4. temperaturewas cooled to −20° C.
  5. stirringstirred for 1 h at 15° C
  6. customReaction
  7. customAfter completion (TLC), reaction
  8. additionmix
  9. temperaturewas cooled to 0° C.
  10. extractionextracted with ethyl acetate (3×100 mL)
  11. dry with materialThe organic layer was dried over anhydrous sodium sulphate
  12. concentrationconcentrated under reduced pressure
  13. customevaporator
  14. customThe crude was purified through column chromatography (4% Methanol:DCM in silica 100-200 mesh, Diameter of column—2.5 cm, Height of silica—approx. 5 inch)

Sources & evidence

ORD record
ord-d73a60be8d8d4e89be509067f580e868
Source dataset
uspto-grants-2012_12
Patent number
US08338408B2

Reaction notes

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