Dimethylformamide → 4-[1-(2-methyl-thiazol-4-ylmethyl)-1H-benzoimidazol-2-yl]-[1,4]diazepane-1-carboxylic acid tert-butyl ester

HRID 2230703Notes

Reaction equation

HRID 2230703 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[NH:19][C:18]3[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=3[N:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C)C=O.[H-].[Na+].Cl.Cl[CH2:33][C:34]1[N:35]=[C:36]([CH3:39])[S:37][CH:38]=1>O>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[N:16]([CH2:33][C:34]3[N:35]=[C:36]([CH3:39])[S:37][CH:38]=3)[C:17]3[CH:23]=[CH:22][CH:21]=[CH:20][C:18]=3[N:19]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 6228Dimethylformamide2×HCID 24758Sodium hydrideHCID 27342034-(Chloromethyl)-2-methyl-1,3-thiazole--hydrogen chloride (1/1)HCID 184646551-t-butoxycarbonyl-4-(1H-benzimidazol-2-yl)[1,4]diazepane

Product 1

HCID 701494834-[1-(2-methyl-thiazol-4-ylmethyl)-1H-benzoimidazol-2-yl]-[1,4]diazepane-1-carboxylic acid tert-butyl esterYield 86.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Treat a solution of 1-(t-butoxycarbonyl)-4-(1H-benzimidazol-2-yl)[1,4]diazepan (0.89 g, 2.77 mmol, Preparation 9) and dimethylformamide (10 mL) with sodium hydride (0.15 g, 3.05 mmol, 49% dispersion in oil ) at room temperature. After 15 minutes, add slowly a solution of 4-chloromethyl-2-methylthiazole hydrochloride (0.56 g, 3.05 mmol, Lancaster Synthesis) and dimethylformamide (10 mL). After stirring 12 hours at room temperature, add water (10 mL) slowly and extract with dichloromethane.(150 mL). Wash the organic phase with water (3×10 mL), dry (Na2SO4) the organic layer, filter, concentrate the filtrate to remove the solvent and purify the residue by chromatography on silica gel eluting with 5% methanol in dichloromethane. Concentrate the desired fractions to afford 1.02 g of 4-[1-(2-methyl-thiazol-4-ylmethyl)-1H-benzoimidazol-2-yl]-[1,4]diazepane-1-carboxylic acid tert-butyl ester.

Workup

  1. extractionextract with dichloromethane
  2. washWash the organic phase with water (3×10 mL)
  3. dry with materialdry (Na2SO4) the organic layer
  4. filtrationfilter
  5. concentrationconcentrate the filtrate
  6. customto remove the solvent
  7. custompurify the residue by chromatography on silica gel eluting with 5% methanol in dichloromethane
  8. concentrationConcentrate the desired fractions

Sources & evidence

ORD record
ord-f32c47b5558042d2ad1a9b03e68b43c6
Source dataset
uspto-grants-2002_07
Patent number
US06423704B1

Reaction notes

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