8-chloro-2-methyl-1H,2H,3H,4H,5H-pyrido(4,3-b)indole → HCID 49779594, compound

HRID 1773264Notes

Reaction equation

HRID 1773264 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=O)C>[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 49779594HCID 49779594, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

8-Chloro-2,3,4,5-tetrahydro-2-methyl-1H-pyrido[4,3-b]indole (1.3 g, 5 mmol) was dissolved in DMF (10 mL) and stirred for 5 min. Sodium hydride (709 mg, 17.7 mmol) was then added to it portionwise under nitrogen. This was followed by addition of 2-butyl-2-(4-fluorophenyl)oxirane (3.4 g, 17.7 mmol) at RT and the reaction mixture was stirred for 18 h. After completion of reaction, the reaction mixture was poured into ice water and the product extracted with EtOAc. The organic layer was washed with water, dried over sodium sulfate and concentrated under reduced pressure to give the crude product which was purified by silica gel (#100-200 mesh) column chromatography using 1% MeOH in DCM as eluent. The pure compound was converted into the oxalate salt. Separation of the (R) and (S) enantiomers was performed by chiral HPLC. 1HNMR (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. stirringthe reaction mixture was stirred for 18 h
  2. customAfter completion of reaction
  3. extractionthe product extracted with EtOAc
  4. washThe organic layer was washed with water
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b200953bde6740d2be583d7db6ae7ad4
Source dataset
uspto-grants-2016_02
Patent number
US09255094B2

Reaction notes

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