Dimethylformamide → HCID 57876230, compound

HRID 509773Notes

Reaction equation

HRID 509773 reaction equation
CN(C=O)C.[H-].[Na+].[CH3:8][N:9]1[CH2:22][CH2:21][C:12]2[NH:13][C:14]3[CH:15]=[CH:16][C:17]([CH3:20])=[CH:18][C:19]=3[C:11]=2[CH2:10]1.Br[CH2:24][CH2:25][CH2:26][C:27]1[CH:28]=[CH:29][C:30]([C:33]([F:36])([F:35])[F:34])=[N:31][CH:32]=1>O>[F:36][C:33]([F:34])([F:35])[C:30]1[N:31]=[CH:32][C:27]([CH2:26][CH2:25][CH2:24][N:13]2[C:14]3[CH:15]=[CH:16][C:17]([CH3:20])=[CH:18][C:19]=3[C:11]3[CH2:10][N:9]([CH3:8])[CH2:22][CH2:21][C:12]2=3)=[CH:28][CH:29]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 2092911H-Pyrido[4,3-b]indole, 2,3,4,5-tetrahydro-2,8-dimethyl-HCID 668695135-(3-Bromopropyl)-2-(trifluoromethyl)pyridine

Product 1

HCID 57876230HCID 57876230, compoundYield 20.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a suspension of DMF (5 mL) and sodium hydride (0.024 g, 0.0006 mol) at 0° c., 2,8-Dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (0.1 g, 0.0005 mol) was added and stirred for 2 h at room temperature, Reaction mix was cooled to −20° c. and 5-(3-Bromo-propyl)-2-trifluoromethyl-pyridine (0.2 g, 0.00075 mol) was added, stirred for 1 h at 15° C. After completion (TLC), reaction mass was cooled to 0° c. and water (10 mL) was added, and 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 (3-4% 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 (0.04 g, 20% yield). 2,8-Dimethyl-5-[3-(6-trifluoromethyl-pyridin-3-yl)-propyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (0.04 g, 0.000103 mol) was dissolved in THF (1.0 mL). A solution of oxalic acid dihydrate (0.012 g, 0.0000952 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 (0.030 g, 61% yield).

Workup

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

Sources & evidence

ORD record
ord-2650300ec4aa4ba3b8bd79ead3d9880c
Source dataset
uspto-grants-2015_08
Patent number
US09096591B2

Reaction notes

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