Dimethylformamide → HCID 22100849, compound

HRID 1458419Notes

Reaction equation

HRID 1458419 reaction equation
[CH:1]([C:4]1[NH:5][C:6]2[C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][C:10]([N:17]([CH:25]3[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]3)[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[CH:9][C:7]=2[N:8]=1)([CH3:3])[CH3:2].[H-].[Na+].BrC[C:35]1[CH:44]=[C:43]2[C:38]([CH:39]=[CH:40][C:41](C#N)=[CH:42]2)=[CH:37][CH:36]=1.[C:47](O[CH2:51][CH3:52])(=O)C.[CH3:53][N:54]([CH:56]=O)C>O>[C:53]([C:39]1[C:38]2[C:43](=[CH:44][CH:35]=[CH:36][CH:37]=2)[C:42]([CH2:47][N:8]2[C:7]3[CH:9]=[C:10]([N:17]([CH:25]4[CH2:26][CH2:27][NH:28][CH2:29][CH2:30]4)[C:18]([O:20][C:21]([CH3:24])([CH3:22])[CH3:23])=[O:19])[CH:11]=[C:12]([C:13]([O:15][CH3:16])=[O:14])[C:6]=3[N:5]=[C:4]2[CH:1]([CH3:3])[CH3:2])=[CH:41][CH:40]=1)#[N:54].[C:56]([C:39]1[C:38]2[C:37](=[CH:36][CH:35]=[CH:44][CH:43]=2)[C:51]([CH2:52][N:5]2[C:6]3[C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][C:10]([N:17]([CH:25]4[CH2:26][CH2:27][NH:28][CH2:29][CH2:30]4)[C:18]([O:20][C:21]([CH3:24])([CH3:22])[CH3:23])=[O:19])=[CH:9][C:7]=3[N:8]=[C:4]2[CH:1]([CH3:3])[CH3:2])=[CH:41][CH:40]=1)#[N:54]

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 98377487-(Bromomethyl)-2-naphthonitrileHCID 178498449HCID 178498449, compound

Product 2

HCID 22100849HCID 22100849, compoundHCID 54030373HCID 54030373, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To 2-isopropyl-4-methoxycarbonyl-6-(N-(tert-butoxycarbonyl)piperidin-4-ylamino)benzimidazole (3.3 g) in DMF (200 mL) was added NaH (0.35 g) at ambient temperature. After stirring at ambient temperature for 30 minutes, the reaction flask was cooled to -10° C. and 7-bromomethyl-2-naphthonitrile (2.2 g) was added. The reaction was allowed to warm to ambient temperature and stirred at ambient temperature for 15 hours. The reaction was worked up between ethyl acetate and H2O. The organic layer was dried, concentrated and purified by silica gel chromatography (hexane/ethyl acetate/CH2Cl2 /methanol, gradient) to afford 1-(4-cyanonaphth-1-yl)methyl-2-isopropyl-4-methoxycarbonyl-6-(N-(tert-butoxycarbonyl)piperidin-4-ylamino)benzimidazole, and 1-(4-cyanonaphth-1-yl)methyl-2-isopropyl-7-methoxycarbonyl-5-(N-(tert-butoxycarbonyl)-piperidin-4-ylamino)benzimidazole.

Workup

  1. temperaturethe reaction flask was cooled to -10° C.
  2. temperatureto warm to ambient temperature
  3. stirringstirred at ambient temperature for 15 hours
  4. customThe organic layer was dried
  5. concentrationconcentrated
  6. custompurified by silica gel chromatography (hexane/ethyl acetate/CH2Cl2 /methanol, gradient)

Sources & evidence

ORD record
ord-ea350aa2182e49299acdeb8144e442db
Source dataset
uspto-grants-1998_12
Patent number
US05849759

Reaction notes

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