Dimethylformamide → 4-{1-[2-(5-methyl-tetrazol-1-yl)-ethyl]-1H-benzoimidazol-2-yl}-[1,4]diazepane-1-carboxylic acid tert-butyl ester

HRID 2230720Notes

Reaction equation

HRID 2230720 reaction equation
[CH3:1][C:2]1[NH:6][N:5]=[N:4][N:3]=1.CN(C)C=O.[H-].[Na+].[C:14]([O:18][C:19]([N:21]1[CH2:27][CH2:26][CH2:25][N:24]([C:28]2[N:32]([CH2:33][CH2:34]OS(C)(=O)=O)[C:31]3[CH:40]=[CH:41][CH:42]=[CH:43][C:30]=3[N:29]=2)[CH2:23][CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15]>C(OCC)(=O)C>[C:14]([O:18][C:19]([N:21]1[CH2:27][CH2:26][CH2:25][N:24]([C:28]2[N:32]([CH2:33][CH2:34][N:3]3[C:2]([CH3:1])=[N:6][N:5]=[N:4]3)[C:31]3[CH:40]=[CH:41][CH:42]=[CH:43][C:30]=3[N:29]=2)[CH2:23][CH2:22]1)=[O:20])([CH3:15])([CH3:16])[CH3:17]

Participants

6

Reactant 4

HCID 6228Dimethylformamide2×HCID 24758Sodium hydrideHCID 18464661HCID 18464661, compoundHCID 178434708HCID 178434708, compound

Product 1

HCID 701476184-{1-[2-(5-methyl-tetrazol-1-yl)-ethyl]-1H-benzoimidazol-2-yl}-[1,4]diazepane-1-carboxylic acid tert-butyl esterYield 34.8%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Treat a stirred solution of 5-methyltetrazole (0.38 g, 4.52 mmol, obtained from TCI US) and dimethylformamide (7 mL) at 0° C. portionwise with sodium hydride (0.19 g, 4.75 mmol, 60% dispersion in oil). Allow to warm to room temperature over one hour and add a solution of 1-(t-butoxycarbonyl)-4-(1-(2-methanesulfonyloxyethyl)-1H-benzimidazol-2-yl)-[1,4]diazepane (0.1.33 g, 3.03 mmol, Preparation 28) and dimethylformamide (7 mL). Heat at 100° C. for 6 hours. Cool, add ethyl acetate (50 mL) and wash with saturated NaHCO3 (3×25 mL) and brine (3×50 mL). Dry (MgSO4) the organic phase, filter and concentrate in vacuo. Purify the residue by chromatography (silica gel, 3.5×50 cm) eluting with ethyl acetate:hexane (1:1) to afford 4-{1-[2-(5-methyl-tetrazol-1-yl}-ethyl]-1H-benzoimidazol-2-yl}-[1,4]diazepane-1-carboxylic acid tert-butyl ester (0.45 g), Rf=0.21 (silica gel, methanol:dichloromethane, 1:1).

Workup

  1. temperatureHeat at 100° C. for 6 hours
  2. temperatureCool
  3. washwash with saturated NaHCO3 (3×25 mL) and brine (3×50 mL)
  4. dry with materialDry (MgSO4) the organic phase
  5. filtrationfilter
  6. concentrationconcentrate in vacuo
  7. customPurify the residue by chromatography (silica gel, 3.5×50 cm)
  8. washeluting with ethyl acetate:hexane (1:1)

Sources & evidence

ORD record
ord-ed1a182d53c74fb2a3f8794f7d9cf790
Source dataset
uspto-grants-2002_07
Patent number
US06423704B1

Reaction notes

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