HCID 54164551, compound → HCID 22100648, compound

HRID 1458416Notes

Reaction equation

HRID 1458416 reaction equation
C(OC([N:8]1[C:12]2[CH:13]=[C:14]([O:21][CH:22]3[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24][CH2:23]3)[C:15]([C:17]([O:19][CH3:20])=[O:18])=[CH:16][C:11]=2[N:10]=[C:9]1[CH3:35])=O)(C)(C)C.C(OC(N1C2C=C(C(OC)=O)C(OC3CCN(C(OC(C)(C)C)=O)CC3)=CC=2N=C1C)=O)(C)(C)C>CO>[CH3:35][C:9]1[NH:10][C:11]2[CH:16]=[C:15]([C:17]([O:19][CH3:20])=[O:18])[C:14]([O:21][CH:22]3[CH2:23][CH2:24][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:26][CH2:27]3)=[CH:13][C:12]=2[N:8]=1

Participants

4

Reactant 2

HCID 54164551HCID 54164551, compoundHCID 54531072HCID 54531072, compound

Product 1

HCID 22100648HCID 22100648, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a mixture of 1-tert-butoxycarbonyl-2-methyl-5-methoxycarbonyl-6-(N-(tert-butoxycarbonyl)piperidin-4-yloxy)benzimidazole and 1-tert-butoxycarbonyl-2-methyl-6-methoxycarbonyl-5-(N-(tert-butoxycarbonyl)piperidin-4-yloxy)benzimidazole (2.5 g) in methanol (200 mL) was bubbled in ammonia at 0° C. After stirring for 2 hours at ambient temperature the reaction mixture was concentrated. The resulting residue was purified by silica gel chromatography (hexane/ethyl acetate/CH2 Cl2 /methanol, gradient) to afford 2-methyl-5-methoxycarbonyl-6-(N-(tert-butoxycarbonyl)piperidin-4-yloxy)benzimidazole. To this product (0.66 g) in DMF (20 mL) was added NaH (0.075 g) at ambient temperature. After stirring at ambient temperature for 30 minutes 7-bromomethyl-2-naphthonitrile (0.5 g) was added at 0° C. The reaction mixture was stirred at ambient temperature for 0.5 hours. The reaction was worked up between ethyl acetate and H2O. The organic layer was dried and concentrated to afford a mixture of 1-(4-cyanonaphth-1-yl)methyl-2-methyl-5-methoxycarbonyl-6-(N-(tert-butoxycarbonyl)piperidin-4-yloxy)benzimidazole and 1-(4-cyanonaphth-1-yl)methyl-2-methyl-6-methoxycarbonyl-5-(N-(tert-butoxycarbonyl)piperidin-4-yloxy)benzimidazole in a ratio of 2 to 1, respectively.

Workup

  1. customwas bubbled in ammonia at 0° C
  2. concentrationwas concentrated
  3. customThe resulting residue was purified by silica gel chromatography (hexane/ethyl acetate/CH2 Cl2 /methanol, gradient)

Sources & evidence

ORD record
ord-b19f355ae8f2498bb8089f1d288b7a99
Source dataset
uspto-grants-1998_12
Patent number
US05849759

Reaction notes

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