Triethylamine → 5-(3-{(2-fluoro-4,5-dimethoxyphenyl)-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-5-oxo-4,5-dihydro-[1,2,4]triazol-1-yl)-1H-pyrazole-4-carboxylic acid ethyl ester

HRID 1161505Notes

Reaction equation

HRID 1161505 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:7]([NH:11][NH2:12])=[N:8][NH:9][CH:10]=1)=[O:5])[CH3:2].C[O:14][C:15](=O)[N:16]=[C:17](SC)[C:18]([C:32]1[CH:37]=[C:36]([O:38][CH3:39])[C:35]([O:40][CH3:41])=[CH:34][C:33]=1[F:42])=[N:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[N:30]=[C:29]([CH3:31])[O:28][N:27]=2)=[CH:22][CH:21]=1.C(N(CC)CC)C>CN(C=O)C>[CH2:1]([O:3][C:4]([C:6]1[CH:10]=[N:9][NH:8][C:7]=1[N:11]1[C:15](=[O:14])[NH:16][C:17]([CH:18]([C:32]2[CH:37]=[C:36]([O:38][CH3:39])[C:35]([O:40][CH3:41])=[CH:34][C:33]=2[F:42])[NH:19][C:20]2[CH:25]=[CH:24][C:23]([C:26]3[N:30]=[C:29]([CH3:31])[O:28][N:27]=3)=[CH:22][CH:21]=2)=[N:12]1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 72312823[2-(2-Fluoro-4,5-dimethoxyphenyl)-2-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylimino]-1-methylsulfanylethylidene]carbamic acid methyl esterHCID 178469936HCID 178469936, compound

Product 1

HCID 1359821385-(3-{(2-fluoro-4,5-dimethoxyphenyl)-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-5-oxo-4,5-dihydro-[1,2,4]triazol-1-yl)-1H-pyrazole-4-carboxylic acid ethyl esterYield 53.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 0.140 g of 3-hydrazino-1H-pyrazole-4-carboxylic acid ethyl ester, 0.236 g of [2-(2-fluoro-4,5-dimethoxyphenyl)-2-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylimino]-1-methylsulfanylethylidene]carbamic acid methyl ester (Example 1d) and 0.209 ml of triethylamine in 6 ml of DMF was heated at 85° C. for 15 hours under a nitrogen atmosphere. After cooling the reaction mixture to room temperature, the solvent was removed under reduced pressure, the residue was dissolved in 7 ml of methanol, and then 0.251 g of sodium cyanotrihydroborate, 0.086 ml of acetic acid and 0.5 g of MS3A were added and the mixture was stirred at room temperature for 20 hours. Next, 100 ml of ethyl acetate and 50 ml of water were added, and the organic layer was washed with 50 ml of water and 50 ml of saturated brine in that order and then dried over anhydrous magnesium sulfate. The desiccating agent was filtered off, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate-methanol) to give the title compound (0.152 g) as a light green solid.

Workup

  1. customthe solvent was removed under reduced pressure
  2. dissolutionthe residue was dissolved in 7 ml of methanol
  3. addition0.251 g of sodium cyanotrihydroborate, 0.086 ml of acetic acid and 0.5 g of MS3A were added
  4. additionNext, 100 ml of ethyl acetate and 50 ml of water were added
  5. washthe organic layer was washed with 50 ml of water and 50 ml of saturated brine in that order
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationThe desiccating agent was filtered off
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customthe residue was purified by silica gel column chromatography (ethyl acetate-methanol)

Sources & evidence

ORD record
ord-c4edf173fca64e37972f805fb28ee18d
Source dataset
uspto-grants-2010_10
Patent number
US07816522B2

Reaction notes

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