Water → methyl 1-methyl-3-({[1-(triphenylmethyl)imidazol-2-yl]amino}methyl)-1H-indazole-6-carboxylate

HRID 1007679Notes

Reaction equation

HRID 1007679 reaction equation
[CH:1]([C:3]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:9][CH:10]=2)[N:5]([CH3:16])[N:4]=1)=O.[C:17]([N:36]1[CH:40]=[CH:39][N:38]=[C:37]1[NH2:41])([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].O>C1(C)C=CC=CC=1>[CH3:16][N:5]1[C:6]2[C:11](=[CH:10][CH:9]=[C:8]([C:12]([O:14][CH3:15])=[O:13])[CH:7]=2)[C:3]([CH2:1][NH:41][C:37]2[N:36]([C:17]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)([C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=3)[C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH:40]=[CH:39][N:38]=2)=[N:4]1

Participants

6

Reactant 4

HCID 962WaterHCID 5049666Sodium triacetoxyborohydrideHCID 103589742-Amino-1-trityl-imidazoleHCID 22598959methyl 3-formyl-1-methyl-1H-indazole-6-carboxylate

Product 1

HCID 22598985methyl 1-methyl-3-({[1-(triphenylmethyl)imidazol-2-yl]amino}methyl)-1H-indazole-6-carboxylate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

The product of Step A (204 mg, 1 mmol) is dissolved in toluene (10 mL) with N-trityl-2-aminoimidazole (357 mg, 1.1 mmol) and heated to reflux with a Dean-Stark trap. Four aliquots of toluene (3 mL each) are removed via distillation at 1.5 hour intervals, being replaced by dry toluene each time, and then the solution is left to reflux for 18 hours. The reaction is cooled to room temperature and sodium triacetoxyborohydride (1 gram, 5 mmol) is added in one portion. The reaction is stirred at room temperature for 24 hours, poured into water, and the layers separated. The aqueous layer is extracted with ethyl acetate and the combined organic layers are washed with saturated bicarbonate, water, and brine, dried over magnesium sulfate, concentrated, and purified by flash chromatography to afford the product.

Workup

  1. temperatureheated
  2. temperatureto reflux with a Dean-Stark trap
  3. customFour aliquots of toluene (3 mL each) are removed via distillation at 1.5 hour intervals
  4. waitthe solution is left
  5. temperatureto reflux for 18 hours
  6. customthe layers separated
  7. extractionThe aqueous layer is extracted with ethyl acetate
  8. washthe combined organic layers are washed with saturated bicarbonate, water, and brine
  9. dry with materialdried over magnesium sulfate
  10. concentrationconcentrated
  11. custompurified by flash chromatography
  12. customto afford the product

Sources & evidence

ORD record
ord-25e31b6c5cb94088aa97b310481ec7dd
Source dataset
uspto-grants-2004_09
Patent number
US06794518B1

Reaction notes

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