Sodium hydride → 1-methyl-2-[N-(4-cyanophenyl)aminomethyl]benzimidazol-5-yl-carboxylic acid-N-(2-pyridyl)-N-[2-(methanesulfonylaminocarbonyl)ethyl]amide

HRID 2288540Notes

Reaction equation

HRID 2288540 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[N:7]([CH2:30][CH2:31][C:32]([OH:34])=O)[C:8]([C:10]1[CH:29]=[CH:28][C:13]2[N:14]([CH3:27])[C:15]([CH2:17][NH:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]#[N:26])=[CH:21][CH:20]=3)=[N:16][C:12]=2[CH:11]=1)=[O:9].C(N1C=CN=C1)(N1C=CN=C1)=O.[CH3:47][S:48]([NH2:51])(=[O:50])=[O:49].[H-].[Na+]>O1CCCC1.CN(C)C=O.O>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[N:7]([CH2:30][CH2:31][C:32]([NH:51][S:48]([CH3:47])(=[O:50])=[O:49])=[O:34])[C:8]([C:10]1[CH:29]=[CH:28][C:13]2[N:14]([CH3:27])[C:15]([CH2:17][NH:18][C:19]3[CH:20]=[CH:21][C:22]([C:25]#[N:26])=[CH:23][CH:24]=3)=[N:16][C:12]=2[CH:11]=1)=[O:9]

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 682631,1'-CarbonyldiimidazoleHCID 72879MethanesulfonamideHCID 18412686N-[[2-[[(4-Cyanophenyl)amino]methyl]-1-methyl-1H-benzimidazol-5-yl]carbonyl]-N-2-pyridinyl-beta-alanine

Product 1

HCID 184125901-methyl-2-[N-(4-cyanophenyl)aminomethyl]benzimidazol-5-yl-carboxylic acid-N-(2-pyridyl)-N-[2-(methanesulfonylaminocarbonyl)ethyl]amide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent2×

Procedure

2.0 g (4.5 mmol) of 1-methyl-2-[N-(4-cyanophenyl)-aminomethyl]-benzimidazol-5-yl-carboxylic acid-N-(2-pyridyl)-N-(2-hydroxycarbonylethyl)-amide and 0.73 g (4.7 mmol) of carbonyldiimidazole were dissolved in 80 ml of tetrahydrofuran and 5 ml of dimethylformamide and stirred for 30 minutes at ambient temperature and for 2 hours at 90° C. In parallel 0.55 g (5.8 mmol) of methansulphonic acid amide and 0.28 g (5.8 mmol) of sodium hydride were suspended in 15 ml of dimethylformamide and stirred for 2 hours at ambient temperature. Then this suspension was added at ambient temperature to the tetrahydrofuran solution. After 12 hours at ambient temperature 50 ml of water were added and the pH value was adjusted to 6.8. The solution was extracted 4× with methylene chloride, the combined organic phases were dried over sodium sulphate and evaporated down. The crude product was chromatographed on silica gel (methylene chloride/ethanol (40:1)). The desired fractions were combined and evaporated down. Yield: 1.05 g (44% of theory), C26H25N7O4S (531.6) Rf value: 0.72 (silica gel; dichloromethane/methanol=9:1)

Workup

  1. extractionThe solution was extracted 4× with methylene chloride
  2. dry with materialthe combined organic phases were dried over sodium sulphate
  3. customevaporated down
  4. customThe crude product was chromatographed on silica gel (methylene chloride/ethanol (40:1))
  5. customevaporated down

Sources & evidence

ORD record
ord-be00532dd9b6445da95e1558e2c4b9c7
Source dataset
uspto-grants-2000_07
Patent number
US06087380

Reaction notes

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