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

HRID 2408593Notes

Reaction equation

HRID 2408593 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][CH:25]=[CH:24][N: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][CH:25]=[CH:24][N: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 10261140Pyridine, 2-(2-methyloxiranyl)- (9CI)

Product 1

HCID 710079251-(2,6-Dimethyl-1,2,3,4-tetrahydro-beta-carbolin-9-yl)-2-pyridin-2-yl-propan-2-olYield 13.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2,6-Dimethyl-2,3,4,9-tetrahydro-1H-β-carboline (500 mg, 2.5 mmol) was dissolved in 20 mL DMF and stirred for 10 min at RT. Sodium hydride (180 mg, 7.5 mmol) was added portionwise at RT and the mixture stirred for 10 min. 2-(2-Methyl-oxiranyl)-pyridine (472 mg, 3.5 mmol) was added dropwise at the same temperature and stirred for 12 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 (3×100 mL). The combined organic layer was washed with water (3×100 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated and the residue was crystallized in hexane to obtain 115 mg of 1-(2,6-dimethyl-1,2,3,4-tetrahydro-β-carbolin-9-yl)-2-pyridin-2-yl-propan-2-ol. 1HNMR (CDCl3, freebase) δ (ppm): 8.51 (d, 1H), 7.65 (t, 1H), 7.29 (d, 1H), 7.22 (d, 1H), 7.20 (s, 1H), 6.95 (d, 1H), 6.85 (d, 1H), 4.9 (bs, 1H), 4.18 (s, 2H), 3.21 (dd, 2H), 2.77 (m, 2H), 2.69 (m, 2H), 2.42 (d, 6H), 1.63 (s, 3H). Separation by chiral HPLC provided enantiomers 16a and 16b. Optical rotations: Compound No. 16a, (−) 5.77 (c 0.52, Chloroform, 98.11% HPLC purity); Compound No. 16b, (+) 5.85 (c 0.51, Chloroform, 98.06% HPLC purity).

Workup

  1. stirringthe mixture stirred for 10 min
  2. stirringstirred for 12 h at RT
  3. customAfter consumption of starting material
  4. customthe reaction mixture was quenched with ice water
  5. extractionextracted with EtOAc (3×100 mL)
  6. washThe combined organic layer was washed with water (3×100 mL)
  7. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  8. concentrationconcentrated
  9. customthe residue was crystallized in hexane

Sources & evidence

ORD record
ord-1b07ee1ad0384cd5887f7296e2c5b74e
Source dataset
uspto-grants-2014_08
Patent number
US08815843B2

Reaction notes

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