Sodium bis(trimethylsilyl)amide → N-cyclohexyl-N-methyl-4-(1H-imidazo[4,5-c]pyridinylmethyl)benzamide

HRID 1646496Notes

Reaction equation

HRID 1646496 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[NH:11]1[C:19]2[CH:18]=[CH:17][N:16]=[CH:15][C:14]=2[N:13]=[CH:12]1.[CH:20]1([N:26]([CH3:37])[C:27](=[O:36])[C:28]2[CH:33]=[CH:32][C:31]([CH2:34]Br)=[CH:30][CH:29]=2)[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1>C1COCC1.C(OCC)(=O)C.CO.O>[CH:20]1([N:26]([CH3:37])[C:27](=[O:36])[C:28]2[CH:33]=[CH:32][C:31]([CH2:34][N:11]3[C:19]4[CH:18]=[CH:17][N:16]=[CH:15][C:14]=4[N:13]=[CH:12]3)=[CH:30][CH:29]=2)[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1

Participants

8

Reactant 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 14797401N-cyclohexyl-N-methyl-4-bromomethylbenzamideHCID 178419860HCID 178419860, compound

Product 1

HCID 14369772N-cyclohexyl-N-methyl-4-(1H-imidazo[4,5-c]pyridinylmethyl)benzamideYield 5.6%

Reagents, catalysts & solvents 4

HCID 887MethanolSolvent2×HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Sodium bis(trimethylsilyl)amide (22 ml of 1 M solution in THF) was added to a stirred solution of imidazo[4,5-c]pyridine (2.60 g, 0.02 mol) in dry THF (200 ml) under argon. A fine white precipitate formed. After 90 m the mixture was treated with purified N-cyclohexyl-N-methyl 4-bromomethylbenzamide (6.20 g, 0.02 mol) dissolved in dry THF (50 ml). The mixture was allowed to warm to ambient temperature and stirred overnight. Methanol (1 ml) was added, followed by water and the product extracted using ethyl acetate (3×150 ml). The combined organic layers were washed with water (2×100 ml), dried over K2CO3 and the solvent removed to give the crude product. Flash chromatography (flash silica: 10% methanol in ethyl acetate) followed by repeated fractional crystallization (6 times from ethyl acetate/DIPE) gave the desired regioisomer N-cyclohexyl-N-methyl 4-(lH-imidazo[4,5-c]pyridin-1-ylmethyl)benzamide (0.39 g, 5%) as an off white crystalline solid.

Workup

  1. customA fine white precipitate formed
  2. extractionthe product extracted
  3. washThe combined organic layers were washed with water (2×100 ml)
  4. dry with materialdried over K2CO3
  5. customthe solvent removed
  6. customto give the crude product
  7. customcrystallization (6 times from ethyl acetate/DIPE)

Sources & evidence

ORD record
ord-7d674723ee174efaa9fd369bc473f6e4
Source dataset
uspto-grants-1993_01
Patent number
US05180724

Reaction notes

Loading…