Sodium hydride → HCID 71268830, compound

HRID 1469437Notes

Reaction equation

HRID 1469437 reaction equation
[CH3:1][N:2]1[CH2:17][CH2:16][C:5]2[NH:6][C:7]3[CH:8]=[CH:9][C:10]([C:13](=[O:15])[CH3:14])=[CH:11][C:12]=3[C:4]=2[CH2:3]1.[H-].[Na+].[O:20]1[CH2:22][CH:21]1[C:23]1[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=1>CN(C=O)C>[OH:20][CH:21]([C:23]1[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=1)[CH2:22][N:6]1[C:7]2[CH:8]=[CH:9][C:10]([C:13](=[O:15])[CH3:14])=[CH:11][C:12]=2[C:4]2[CH2:3][N:2]([CH3:1])[CH2:17][CH2:16][C:5]1=2

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 109534834-(Oxiran-2-yl)pyridineHCID 71268754HCID 71268754, compound

Product 1

HCID 71268830HCID 71268830, compoundYield 4.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a stirred solution of 1-(2,3,4,5-tetrahydro-2-methyl-1H-pyrido[4,3-b]indol-8-yl)ethanone (80 mg, 0.35 mmol) in DMF (2 mL) was added sodium hydride (60%, 42 mg, 1.05 mmol). After stirring for 10 min, a solution of 4-(oxiran-2-yl)pyridine (62 mg, 0.51 mmol) in DMF (1 mL) was added into the reaction mixture, and stirred at RT for 4 h. The reaction mixture was quenched with ice water and extracted with EtOAc. The organic layer was washed with water, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue obtain was purified by crystallization with ether to yield 1-(2,3,4,5-tetrahydro-5-(2-hydroxy-2-(pyridin-4-yl)ethyl)-2-methyl-1H-pyrido[4,3-b]indol-8-yl)ethanone (6 mg). 1H NMR (CDCl3, freebase) δ (ppm): 8.5 (d, 2H), 7.95 (s, 1H), 7.73 (d, 1H), 7.26 (d, 2H), 7.12 (d, 1H), 4.78 (t, 1H), 4.8 (d, 2H), 3.49 (m, 2H), 2.90 (m, 1H), 2.8 (q, 2H), 2.79 (s, 3H), 2.6 (m, 1H), 2.37 (s, 3H). Separation by chiral HPLC provided enantiomers 49a and 49b.

Workup

  1. stirringstirred at RT for 4 h
  2. customThe reaction mixture was quenched with ice water
  3. extractionextracted with EtOAc
  4. washThe organic layer was washed with water
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue obtain
  8. customwas purified by crystallization with ether

Sources & evidence

ORD record
ord-a9a26880468c447abd9b0c933c40c2af
Source dataset
uspto-grants-2015_04
Patent number
US09006263B2

Reaction notes

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