8-chloro-2-methyl-1H,2H,3H,4H,5H-pyrido(4,3-b)indole → 1-(8-Chloro-2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-2-(4-fluorophenyl)hexan-2-ol

HRID 1773289Notes

Reaction equation

HRID 1773289 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[NH:7][C:6]3[CH2:11][CH2:12][N:13]([CH3:15])[CH2:14][C:5]=3[C:4]=2[CH:3]=1.[H-].[Na+].[CH2:18]([C:22]1([C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)[CH2:24][O:23]1)[CH2:19][CH2:20][CH3:21]>CN(C)C=O>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]([CH2:24][C:22]([C:25]3[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=3)([OH:23])[CH2:18][CH2:19][CH2:20][CH3:21])[C:6]3[CH2:11][CH2:12][N:13]([CH3:15])[CH2:14][C:5]=3[C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 196158-chloro-2-methyl-1H,2H,3H,4H,5H-pyrido(4,3-b)indoleHCID 24758Sodium hydrideHCID 86644763HCID 86644763, compound

Product 1

HCID 497795941-(8-Chloro-2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-2-(4-fluorophenyl)hexan-2-ol

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 8-chloro-2,3,4,5-tetrahydro-2-methyl-1H-pyrido[4,3-b]indole (1.3 g, 5 mmol) in dimethylformamide (10 mL) was added sodium hydride (709 mg, 17.7 mmol) in portions followed by addition of 2-butyl-2-(4-fluorophenyl)oxirane (3.4 g, 17.7 mmol), and the reaction mixture was stirred for 18 h at RT. After completion, reaction mixture was poured into ice water and extracted with EtOAc. The organic layer was washed with water, dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford crude material, which was purified by silica gel (100-200 mesh) column chromatography using 1% MeOH-DCM as eluent. The pure compound was converted into oxalate salt by treatment with oxalic acid in ethanol. 1H NMR (CDCl3, Oxalate salt) d (ppm): 7.30 (m, 3H), 7.10 (d, 1H), 6.95 (m, 3H), 4.20 (m, 1H), 4.0 (m, 1H), 3.62 (m, 2H), 2.70 (m, 3H), 2.50 (s, 3H), 2.20 (m, 1H), 2.0 (m, 1H), 1.80 (m, 1H), 1.22 (m, 3H), 1.0 (m, 1H), 0.80 (t, 3H).

Workup

  1. customAfter completion, reaction mixture
  2. extractionextracted with EtOAc
  3. washThe organic layer was washed with water
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customto afford crude material, which
  7. customwas purified by silica gel (100-200 mesh) column chromatography

Sources & evidence

ORD record
ord-dc5383b49f42431ba785d36879ef1df7
Source dataset
uspto-grants-2016_02
Patent number
US09255094B2

Reaction notes

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