Dimethylformamide → 4-(3-{(5-Ethoxy-6-methoxypyridin-3-yl)-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-5-oxo-4,5-dihydro-[1,2,4]triazol-1-yl)thiazole-5-carboxylic acid ethyl ester

HRID 1161549Notes

Reaction equation

HRID 1161549 reaction equation
CN(C=O)C.C[O:7][C:8](=O)[N:9]=[C:10](SC)[C:11]([C:25]1[CH:26]=[N:27][C:28]([O:34][CH3:35])=[C:29]([O:31][CH2:32][CH3:33])[CH:30]=1)=[N:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[N:23]=[C:22]([CH3:24])[O:21][N:20]=2)=[CH:15][CH:14]=1.[CH2:39]([O:41][C:42]([C:44]1[S:48][CH:47]=[N:46][C:45]=1[NH:49][NH2:50])=[O:43])[CH3:40]>C(N(CC)CC)C>[CH2:39]([O:41][C:42]([C:44]1[S:48][CH:47]=[N:46][C:45]=1[N:49]1[C:8](=[O:7])[NH:9][C:10]([CH:11]([C:25]2[CH:26]=[N:27][C:28]([O:34][CH3:35])=[C:29]([O:31][CH2:32][CH3:33])[CH:30]=2)[NH:12][C:13]2[CH:14]=[CH:15][C:16]([C:19]3[N:23]=[C:22]([CH3:24])[O:21][N:20]=3)=[CH:17][CH:18]=2)=[N:50]1)=[O:43])[CH3:40]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 595170574-Hydrazinothiazole-5-carboxylic acid ethyl esterHCID 72312848{2-(5-Ethoxy-6-methoxypyridin-3-yl)-2-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylimino]-1-methylsulfanylethylidene}carbamic acid methyl ester

Product 1

HCID 1359821304-(3-{(5-Ethoxy-6-methoxypyridin-3-yl)-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-5-oxo-4,5-dihydro-[1,2,4]triazol-1-yl)thiazole-5-carboxylic acid ethyl esterYield 45.1%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Conditions

Temperature
85 °C

Procedure

To 4 ml of a DMF solution containing 117 mg of {2-(5-ethoxy-6-methoxypyridin-3-yl)-2-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylimino]-1-methylsulfanylethylidene}carbamic acid methyl ester (Example 160a), 52 mg of 4-hydrazinothiazole-5-carboxylic acid ethyl ester and 0.038 ml of triethylamine were added. The mixture was stirred at 85° C. for 16 hours under a nitrogen atmosphere. The reaction mixture was concentrated. The residue was dissolved in 10 ml of methanol and 0.05 ml of acetic acid, and then 125 mg of sodium cyanotrihydroborate was further added thereto. The mixture was stirred at room temperature for 15 hours, and then 100 ml of ethyl acetate and 50 ml of water were added thereto. The organic layer was washed with 50 ml of water and then with 50 ml of saturated brine and then dried over anhydrous magnesium sulfate. The desiccating agent was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by NAM silica gel column chromatography (methanol-ethyl acetate) to give the title compound (65 mg).

Workup

  1. additionwere added
  2. concentrationThe reaction mixture was concentrated
  3. dissolutionThe residue was dissolved in 10 ml of methanol
  4. addition0.05 ml of acetic acid, and then 125 mg of sodium cyanotrihydroborate was further added
  5. stirringThe mixture was stirred at room temperature for 15 hours
  6. addition100 ml of ethyl acetate and 50 ml of water were added
  7. washThe organic layer was washed with 50 ml of water
  8. dry with materialwith 50 ml of saturated brine and then dried over anhydrous magnesium sulfate
  9. customThe desiccating agent was removed by filtration
  10. concentrationthe filtrate was concentrated under reduced pressure
  11. customThe residue was purified by NAM silica gel column chromatography (methanol-ethyl acetate)

Sources & evidence

ORD record
ord-ad50f8b3c02042828c1d0334bcb1efd4
Source dataset
uspto-grants-2010_10
Patent number
US07816522B2

Reaction notes

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