Sodium hydride → HCID 68387746, compound

HRID 1630490Notes

Reaction equation

HRID 1630490 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[CH2:3]1.[H-].[Na+].[CH3:18][C:19]1([C:22]2[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=2)[CH2:21][O:20]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]([CH2:18][C:19]([C:22]3[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=3)([OH:20])[CH3:21])[C:4]=2[CH2:3]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 7571332,3,4,9-Tetrahydro-2,6-dimethyl-1H-pyrido[3,4-b]indoleHCID 123953864-(2-Methyloxiran-2-yl)pyridine

Product 1

HCID 68387746HCID 68387746, compoundYield 20.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

2,6-Dimethyl-2,3,4,9-tetrahydro-1H-β-carboline (500 mg, 2.5 mmol) was dissolved in 10 mL DMF and stirred for 10 min at 0° C. Sodium hydride (300 mg, 7.5 mmol) was added portionwise at RT and stirred for 10 min. 4-(2-Methyl-oxiranyl)-pyridine (472 mg, 3.5 mmol) was added dropwise at the same temperature and stirred for 4 h at RT. The reaction was monitored by TLC & LCMS. After consumption of starting material, the reaction mixture was quenched with ice water and extracted with EtOAc (2×60 mL). The combined organic layer was washed with water (5×75 mL), dried over anhydrous sodium sulfate and concentrated and the residue was crystallized in EtOH and hexane to obtain 175 mg of 1-(2,6-dimethyl-1,2,3,4-tetrahydro-β-carbolin-9-yl)-2-pyridin-4-yl-propan-2-ol. 1H NMR (CDCl3, Free base) δ (ppm): 8.58 (d, 2H), 7.40 (d, 2H), 7.25 (s, 1H), 7.16 (d, 1H), 6.92 (d, 1H), 4.18-4.0 (dd, 2H), 3.50-3.38 (dd, 2H), 2.80 (m, 2H), 2.70 (m, 2H), 2.44 (s, 3H), 2.42 (s, 3H), 1.58 (s, 3H). Separation by chiral HPLC provided enantiomers 19a and 19b. Optical rotations: Compound 19a, (+)22.35 (c 0.58, Chloroform, 98.36% HPLC purity); Compound 19b, (−)22.43 (c 0.55, Chloroform, 99.09% HPLC purity).

Workup

  1. stirringstirred for 10 min
  2. stirringstirred for 4 h at RT
  3. customAfter consumption of starting material
  4. customthe reaction mixture was quenched with ice water
  5. extractionextracted with EtOAc (2×60 mL)
  6. washThe combined organic layer was washed with water (5×75 mL)
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated
  9. customthe residue was crystallized in EtOH

Sources & evidence

ORD record
ord-16dcaf6a2132469aaa44d18a912d7b78
Source dataset
uspto-grants-2014_07
Patent number
US08791132B2

Reaction notes

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