1-Pentanesulfonamide → 1-(Isoquinolin-3-ylmethyl)-2-methyl-6-(1-pentane-sulfonylcarbamoyl)benzimidazole

HRID 2229459

Reaction equation

HRID 2229459 reaction equation
[C:1]([C:4]1[CH:5]=[CH:6][C:7]2[N:11]=[C:10]([CH3:12])[N:9]([CH2:13][C:14]3[N:15]=[CH:16][C:17]4[C:22]([CH:23]=3)=[CH:21][CH:20]=[CH:19][CH:18]=4)[C:8]=2[CH:24]=1)(O)=[O:2].[CH2:25]([S:30]([NH2:33])(=[O:32])=[O:31])[CH2:26][CH2:27][CH2:28][CH3:29]>CN(C)C=O>[CH:16]1[C:17]2[C:22](=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:23]=[C:14]([CH2:13][N:9]2[C:8]3[CH:24]=[C:4]([C:1](=[O:2])[NH:33][S:30]([CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])(=[O:32])=[O:31])[CH:5]=[CH:6][C:7]=3[N:11]=[C:10]2[CH3:12])[N:15]=1

Participants

4

Reactant 2

HCID 109206961-PentanesulfonamideHCID 120517556-Carboxy-1-(isoquinolin-3-ylmethyl)-2-methylbenzimidazole

Product 1

HCID 98465941-(Isoquinolin-3-ylmethyl)-2-methyl-6-(1-pentane-sulfonylcarbamoyl)benzimidazoleYield 24.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N,N′-carbonyldiimidazole (0.324 g) was added to a solution of 6-carboxy-1-(isoquinolin-3-ylmethyl)-2-methylbenzimidazole (0.413 g) as obtained in Production Example 5 in N,N-dimethylformamide (10 ml) all at once and the mixture was stirred at room temperature for 1.5 hour. Then, 1-pentanesulfonamide (0.302 g) and diazabicyclo-undecene (0.304 g) were added thereto, and the resulting mixture was stirred at 100° C. for 6.5 hour. The reaction solution was concentrated, brine was added to the concentrate, and the mixture was extracted with chloroform. The organic layer was concentrated and the residue was purified by silica gel column chromatography (eluate: methanol/chloroform=1/19) followed by recrystallization from hexane/ethyl acetate (2/3) to yield the desired compound, 1-(isoquinolin-3-ylmethyl)-2-methyl-6-(1-pentanesulfonyl-carbamoyl)benzimidazole (13) (0.142 g).

Workup

  1. stirringthe resulting mixture was stirred at 100° C. for 6.5 hour
  2. concentrationThe reaction solution was concentrated
  3. additionbrine was added to the concentrate
  4. extractionthe mixture was extracted with chloroform
  5. concentrationThe organic layer was concentrated
  6. customthe residue was purified by silica gel column chromatography (eluate: methanol/chloroform=1/19)
  7. customfollowed by recrystallization from hexane/ethyl acetate (2/3)

Sources & evidence

ORD record
ord-2c97d0e2135741fa895f5966314f5042
Source dataset
uspto-grants-2002_07
Patent number
US06420409B1

Linked notes

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