Methyl iodide → 2-(4-Chlorobenzoyl)-9-methyl-1,2,3,4-tetrahydro-pyrido[3,4-b]indole-3-carboxylic acid

HRID 2369345Notes

Reaction equation

HRID 2369345 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:28]=[CH:27][C:7]([C:8]([N:10]2[CH:22]([C:23]([O:25]C)=[O:24])[CH2:21][C:20]3[C:19]4[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=4)[NH:13][C:12]=3[CH2:11]2)=[O:9])=[CH:6][CH:5]=1.I[CH3:30].[H-]>CN(C=O)C.CO>[Cl:3][C:4]1[CH:5]=[CH:6][C:7]([C:8]([N:10]2[CH:22]([C:23]([OH:25])=[O:24])[CH2:21][C:20]3[C:19]4[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=4)[N:13]([CH3:30])[C:12]=3[CH2:11]2)=[O:9])=[CH:27][CH:28]=1

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 166653HydrideHCID 15626677methyl 2-(4-chlorobenzoyl)-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylate

Product 1

HCID 715748272-(4-Chlorobenzoyl)-9-methyl-1,2,3,4-tetrahydro-pyrido[3,4-b]indole-3-carboxylic acid

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

To a suspension of NaH (0.96 g, 40.0 mmol) in dry DMF (150 ml) was added portionwise methyl 2-(4-chlorobenzoyl)-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylate (7.3 g, 20.0 mmol) at 0° C. to 5° C. After being stirred for 15 min, iodomethane (2.8 g, 20.0 mmol) was added and the reaction mixture was stirred for additional 1 h in an ice bath. The mixture was then stirred at room temperature for 9 h. The excess of hydride was decomposed with methanol and the reaction mixture was then evaporated to dryness in vacuo. The residue was recrystallized from MeOH to give 2-(4-chlorobenzoyl)-9-methyl-1,2,3,4-tetrahydro-pyrido[3,4-b]indole-3-carboxylic acid, 5.4 g (74%); mp 262-263° C. 1H NMR (Acetic acid-d4) δ 3.18 (1H, m, CH2), 3.56 (1H, m, CH2), 3.45 and 3.68 (3H, s, NMe), 4.64 and 5.40 (1H, d, J=15.8 Hz, NCH2), 4.70 and 4.93 (1H, d, J=17.1 Hz, NCH2), 5.02 and 6.12 (1H, d, J=5.4 Hz, CH), 7.04-7.07 (1H, m, ArH), 7.15-7.18 (1H, m, ArH), 7.31-7.33 (1H, m, ArH), 7.45-7.47 (1H, m, ArH), 7.50-7.55 (3H, m, 3×ArH), 7.59-7.61 (1H, m, ArH). Anal. Calcd for (C20H17ClN2O3): C, 65.13; H, 4.65; N, 7.60. Found: C, 64.77; H, 4.79; N, 7.68.

Workup

  1. stirringthe reaction mixture was stirred for additional 1 h in an ice bath
  2. stirringThe mixture was then stirred at room temperature for 9 h
  3. customthe reaction mixture was then evaporated to dryness in vacuo
  4. customThe residue was recrystallized from MeOH

Sources & evidence

ORD record
ord-b0ef6220ab944bb09de24ae41f75f04d
Source dataset
uspto-grants-2014_04
Patent number
US08703951B2

Reaction notes

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