Dimethylformamide → 5-(3-{(5-Fluoro-8-methoxychroman-6-yl)-[4-(5-trifluoromethyl-[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 1161554Notes

Reaction equation

HRID 1161554 reaction equation
CN(C=O)C.CO[C:8](=[O:43])[N:9]=[C:10](SC)[C:11]([C:28]1[C:29]([F:40])=[C:30]2[C:35](=[C:36]([O:38][CH3:39])[CH:37]=1)[O:34][CH2:33][CH2:32][CH2:31]2)=[N:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[N:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[O:21][N:20]=2)=[CH:15][CH:14]=1.Cl.Cl.[CH2:46]([O:48][C:49]([C:51]1[C:52]([NH:56][NH2:57])=[N:53][NH:54][CH:55]=1)=[O:50])[CH3:47]>C(N(CC)CC)C>[CH2:46]([O:48][C:49]([C:51]1[CH:55]=[N:54][NH:53][C:52]=1[N:56]1[C:8](=[O:43])[NH:9][C:10]([CH:11]([C:28]2[C:29]([F:40])=[C:30]3[C:35](=[C:36]([O:38][CH3:39])[CH:37]=2)[O:34][CH2:33][CH2:32][CH2:31]3)[NH:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]3[N:23]=[C:22]([C:24]([F:27])([F:25])[F:26])[O:21][N:20]=3)=[CH:15][CH:14]=2)=[N:57]1)=[O:50])[CH3:47]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 72312756[2-(5-Fluoro-8-methoxychroman-6-yl)-2-[4-(5-trifluoromethyl-[1,2,4]oxadiazol-3-yl)phenylimino]-1-methylsulfanylethylidene]carbamic acid methyl esterHCID 178469938HCID 178469938, compound

Product 1

HCID 1359821775-(3-{(5-Fluoro-8-methoxychroman-6-yl)-[4-(5-trifluoromethyl-[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 20.9%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Conditions

Temperature
85 °C

Procedure

To 5 ml of a DMF solution containing 160 mg of [2-(5-fluoro-8-methoxychroman-6-yl)-2-[4-(5-trifluoromethyl-[1,2,4]oxadiazol-3-yl)phenylimino]-1-methylsulfanylethylidene]carbamic acid methyl ester, 87 mg of 3-hydrazino-1H-pyrazole-4-carboxylic acid ethyl ester bishydrochloride (Example (157b)) and 0.124 ml of triethylamine were added. The resulting mixture was stirred at 85° C. for 16 hours under a nitrogen atmosphere. The reaction mixture was concentrated. The residue was dissolved in 8 ml of methanol and 0.068 ml of acetic acid, and then 187 mg of sodium cyanotrihydroborate was 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 was 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 (39 mg).

Workup

  1. additionwere added
  2. concentrationThe reaction mixture was concentrated
  3. dissolutionThe residue was dissolved in 8 ml of methanol
  4. addition0.068 ml of acetic acid, and then 187 mg of sodium cyanotrihydroborate was 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 was 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-dbd671742f9c4c15aac4537a5f5ad92f
Source dataset
uspto-grants-2010_10
Patent number
US07816522B2

Reaction notes

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