1-Methylpiperazine → [5-amino-1-(2-methyl-1H-benzimidazol-5-yl)-1H-pyrazol-4-yl]-[6-(4-methyl-piperazin-1-ylmethyl)-1-(toluene-4-sulfonyl)-1H-indol-2-yl]-methanone

HRID 74449Notes

Reaction equation

HRID 74449 reaction equation
[NH2:1][C:2]1[N:6]([C:7]2[CH:16]=[CH:15][C:10]3[NH:11][C:12]([CH3:14])=[N:13][C:9]=3[CH:8]=2)[N:5]=[CH:4][C:3]=1[C:17]([C:19]1[N:20]([S:30]([C:33]2[CH:38]=[CH:37][C:36]([CH3:39])=[CH:35][CH:34]=2)(=[O:32])=[O:31])[C:21]2[C:26]([CH:27]=1)=[CH:25][CH:24]=[C:23]([CH:28]=O)[CH:22]=2)=[O:18].[CH3:40][N:41]1[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>ClCCl>[NH2:1][C:2]1[N:6]([C:7]2[CH:16]=[CH:15][C:10]3[NH:11][C:12]([CH3:14])=[N:13][C:9]=3[CH:8]=2)[N:5]=[CH:4][C:3]=1[C:17]([C:19]1[N:20]([S:30]([C:33]2[CH:34]=[CH:35][C:36]([CH3:39])=[CH:37][CH:38]=2)(=[O:32])=[O:31])[C:21]2[C:26]([CH:27]=1)=[CH:25][CH:24]=[C:23]([CH2:28][N:44]1[CH2:45][CH2:46][N:41]([CH3:40])[CH2:42][CH2:43]1)[CH:22]=2)=[O:18]

Participants

6

Reactant 4

HCID 531671-MethylpiperazineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 178427387HCID 178427387, compound

Product 1

HCID 178427386[5-amino-1-(2-methyl-1H-benzimidazol-5-yl)-1H-pyrazol-4-yl]-[6-(4-methyl-piperazin-1-ylmethyl)-1-(toluene-4-sulfonyl)-1H-indol-2-yl]-methanoneYield 86.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-[5-Amino-1-(2-methyl-1H-benzimidazol-5-yl)-1H-pyrazole-4-carbonyl]-1-(toluene-4-sulfonyl)-1H-indole-6-carbaldehyde (29 mg, 0.054 mmol), 1-methylpiperazine (7 μl, 0.066 mmol), and sodium triacetoxyborohydride (17 mg, 0.083 mmol) were dissolved in anhydrous dichloromethane (0.5 ml) and stirred at room temperature under a nitrogen atmosphere for 14 hours. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture. Then, the mixture was extracted with ethyl acetate. The organic layer was isolated, washed with a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate. The desiccant was removed by filtration. The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (dichloromethane/methanol=100/15) to give [5-amino-1-(2-methyl-1H-benzimidazol-5-yl)-1H-pyrazol-4-yl]-[6-(4-methyl-piperazin-1-ylmethyl)-1-(toluene-4-sulfonyl)-1H-indol-2-yl]-methanone as a yellow solid (29 mg, 86%).

Workup

  1. extractionThen, the mixture was extracted with ethyl acetate
  2. customThe organic layer was isolated
  3. washwashed with a saturated aqueous solution of sodium chloride
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe desiccant was removed by filtration
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customThe resulting residue was purified by silica gel column chromatography (dichloromethane/methanol=100/15)

Sources & evidence

ORD record
ord-db57066d0bbf4d3f92d14990db6e1399
Source dataset
uspto-grants-2014_09
Patent number
US08829199B2

Reaction notes

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