Methyl iodide → HCID 57950425, compound

HRID 1020577Notes

Reaction equation

HRID 1020577 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]1[CH2:11][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:13][CH2:14][C:5]2=1.[H-].[Na+].[CH3:24]I>CN(C=O)C.C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH3:24])[C:6]1[CH2:11][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:13][CH2:14][C:5]2=1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 57950460tert-Butyl 6-bromo-3,4-dihydro-1H-pyrido[3,4-b]indole-2(9H)-carboxylate

Product 1

HCID 57950425HCID 57950425, compoundYield 62.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

tert-Butyl 6-bromo-3,4-dihydro-1H-pyrido[3,4-b]indole-2(9H)-carboxylate (1.15 g, 3.26 mmol) was dissolved in DMF (20 mL) and sodium hydride (60% weight dispersion in mineral oil, 196 mg, 4.89 mmol) was added. After 1 h, methyl iodide (0.30 mL, 4.9 mmol) was added and the reaction mixture was stirred for a further 30 min. The mixture was diluted with methylene chloride and washed with 5% lithium chloride solution (5×), dried over Na2SO4 and concentrated. Purification by flash column chromatography (silica gel, hexanes/ethyl acetate, 97:3 to 75:25) gave the title compound (740 mg, 36%) as a yellow solid: 1H NMR (500 MHz, CDCl3) δ 7.58 (s, 1H), 7.24 (d overlapped by solvent, J=8.5, 1H), 7.14 (d, J=8.5, 1H), 4.67-4.53 (br m, 2H), 3.79-3.67 (br m, 2H), 3.60 (s, 3H), 2.78-2.66 (br m, 2H), 1.51 (s, 9H).

Workup

  1. washwashed with 5% lithium chloride solution (5×)
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated
  4. customPurification by flash column chromatography (silica gel, hexanes/ethyl acetate, 97:3 to 75:25)

Sources & evidence

ORD record
ord-0b3adf500e054f3cac5700809455e02b
Source dataset
uspto-grants-2014_05
Patent number
US08716308B2

Reaction notes

Loading…