Sodium hydride → 1-(2,6-Dimethyl-1-phenyl-1,2,3,4-tetrahydro-beta-carbolin-9-yl)-2-pyridin-3-yl-propan-2-ol

HRID 2408704Notes

Reaction equation

HRID 2408704 reaction equation
[CH3:1][N:2]1[CH2:14][CH2:13][C:12]2[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([CH3:15])[CH:10]=3)[NH:5][C:4]=2[CH:3]1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[H-].[Na+].[CH3:24][C:25]1([C:28]2[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=2)[CH2:27][O:26]1>CN(C=O)C>[CH3:1][N:2]1[CH2:14][CH2:13][C:12]2[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([CH3:15])[CH:10]=3)[N:5]([CH2:24][C:25]([C:28]3[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=3)([OH:26])[CH3:27])[C:4]=2[CH:3]1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 230811803-(2-Methyloxiran-2-yl)pyridineHCID 66911787HCID 66911787, compound

Product 1

HCID 710078811-(2,6-Dimethyl-1-phenyl-1,2,3,4-tetrahydro-beta-carbolin-9-yl)-2-pyridin-3-yl-propan-2-olYield 27%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

2,6-Dimethyl-1-phenyl-2,3,4,9-tetrahydro-1H-β-carboline (300 mg, 1.08 mmol) was dissolved in DMF (4 mL). Sodium hydride (172 mg, 4.32 mmol) was added and the mixture was stirred at RT for 30 min. 3-(2-Methyl-oxiranyl)-pyridine (733 mg, 5.43 mmol) in 1 mL DMF was added dropwise into the reaction mixture, which was stirred for 5 h at RT. The reaction was monitored by TLC and LCMS. After consumption of starting material, the reaction was quenched with ice and extracted with EtOAc (2×100 mL). The organic layer was washed with water (2×100 mL), dried over anhydrous sodium sulfate and concentrated to obtain the crude that was purified by column chromatography (silica gel 100-200 mesh, Eluent: 6% MeOH in DCM) to obtain 120 mg of 1-(2,6-dimethyl-1-phenyl-1,2,3,4-tetrahydro-β-carbolin-9-yl)-2-pyridin-3-yl-propan-2-ol (racemate) and followed by chiral separation. 1H NMR (CD3OD, TFA salt) δ (ppm): 8.25 (s, 1H), 8.2 (d, 1H), 7.6 (d, 1H), 7.4 (m, 3H), 7.2 (s, 1H), 7.19 (m, 3H), 6.65 (d, 1H), 6.4 (d, 1H), 5.5 (s, 1H), 4.0 (d, 1H), 3.43 (d, 1H), 3.2 (m, 1H), 3.0 (m, 3H), 2.6 (s, 3H), 2.3 (s, 3H), 1.6 (s, 3H). Separation by chiral HPLC provided diastereomers II-112a-b.

Workup

  1. stirringwas stirred for 5 h at RT
  2. customAfter consumption of starting material
  3. customthe reaction was quenched with ice
  4. extractionextracted with EtOAc (2×100 mL)
  5. washThe organic layer was washed with water (2×100 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. customto obtain the crude that
  9. customwas purified by column chromatography (silica gel 100-200 mesh, Eluent: 6% MeOH in DCM)

Sources & evidence

ORD record
ord-5d0340535e36493282a3bc9d83ad360c
Source dataset
uspto-grants-2014_08
Patent number
US08815843B2

Reaction notes

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