Pyrazole → HCID 70147913, compound

HRID 2230717Notes

Reaction equation

HRID 2230717 reaction equation
[NH:1]1[CH:5]=[CH:4][CH:3]=[N:2]1.CN(C)C=O.[H-].[Na+].[C:13]([O:17][C:18]([N:20]1[CH2:26][CH2:25][CH2:24][N:23]([C:27]2[N:31]([CH2:32][CH2:33]OS(C)(=O)=O)[C:30]3[CH:39]=[CH:40][CH:41]=[CH:42][C:29]=3[N:28]=2)[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14]>ClCCl>[C:13]([O:17][C:18]([N:20]1[CH2:26][CH2:25][CH2:24][N:23]([C:27]2[N:31]([CH2:32][CH2:33][N:1]3[CH:5]=[CH:4][CH:3]=[N:2]3)[C:30]3[CH:39]=[CH:40][CH:41]=[CH:42][C:29]=3[N:28]=2)[CH2:22][CH2:21]1)=[O:19])([CH3:14])([CH3:15])[CH3:16]

Participants

6

Reactant 4

HCID 1048PyrazoleHCID 6228Dimethylformamide2×HCID 24758Sodium hydrideHCID 18464661HCID 18464661, compound

Product 1

HCID 70147913HCID 70147913, compoundYield 81.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
75 °C

Procedure

Treat a stirred solution of pyrazole (0.22 g, 3.18 mmol, Aldrich Chemical Company) and dimethylformamide (5 mL) at room temperature portionwise with sodium hydride (0.15 g, 3.18 mmol). After 30 minutes, slowly add a solution of 1-(t-butoxycarbonyl)-4-(1-(2-methanesulfonyloxyethyl)-1H-benzimidazol-2-yl)-[1,4]diazepane (0.93 g, 2.12 mmol, Preparation 28) and dimethylformamide, and then heat at 75° C. for 12 hours. Cool, add dichloromethane (100 mL) and wash with water (2×20 mL). Dry (Na2SO4) the organic phase, filter and concentrate. Dry the residue under high vacuum at 100° C. to remove residual dimethylformamide. Purify the residue by radial chromatography (silica gel, ethyl acetate:hexane, 1:1) to afford 4-[1-(2-pyrazol-1-yl-ethyl)-1H-benzoimidazol-2-yl]-[1,4]diazepane-1-carboxylic acid tert-butyl ester (0.71 g), Rf=0.44 (silica gel, ethyl acetate).

Workup

  1. temperatureCool
  2. washwash with water (2×20 mL)
  3. dry with materialDry (Na2SO4) the organic phase
  4. filtrationfilter
  5. concentrationconcentrate
  6. customDry the residue under high vacuum at 100° C.
  7. customto remove residual dimethylformamide
  8. customPurify the residue by radial chromatography (silica gel, ethyl acetate:hexane, 1:1)

Sources & evidence

ORD record
ord-c2a81fef86d64d29993e62915f04cb0d
Source dataset
uspto-grants-2002_07
Patent number
US06423704B1

Reaction notes

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