Triethylamine → 5-{(9-methoxy-3,4-dihydro-2H-benzo[b][1,4]dioxepin-7-yl)-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl]-2-(3-nitropyridin-2-yl)-2,4-dihydro-[1,2,4]triazol-3-one

HRID 1161444Notes

Reaction equation

HRID 1161444 reaction equation
[N+:1]([C:4]1[C:5]([NH:10][NH2:11])=[N:6][CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].C(N(CC)CC)C.C[O:20][C:21](=O)[N:22]=[C:23](SC)[C:24]([C:38]1[CH:48]=[C:47]([O:49][CH3:50])[C:41]2[O:42][CH2:43][CH2:44][CH2:45][O:46][C:40]=2[CH:39]=1)=[N:25][C:26]1[CH:31]=[CH:30][C:29]([C:32]2[N:36]=[C:35]([CH3:37])[O:34][N:33]=2)=[CH:28][CH:27]=1>CN(C=O)C>[CH3:50][O:49][C:47]1[C:41]2[O:42][CH2:43][CH2:44][CH2:45][O:46][C:40]=2[CH:39]=[C:38]([CH:24]([NH:25][C:26]2[CH:31]=[CH:30][C:29]([C:32]3[N:36]=[C:35]([CH3:37])[O:34][N:33]=3)=[CH:28][CH:27]=2)[C:23]2[NH:22][C:21](=[O:20])[N:10]([C:5]3[C:4]([N+:1]([O-:3])=[O:2])=[CH:9][CH:8]=[CH:7][N:6]=3)[N:11]=2)[CH:48]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 35789352-Hydrazinyl-3-nitropyridineHCID 72312720[2-(9-methoxy-3,4-dihydro-2H-benzo[b][1,4]dioxepin-7-yl)-2-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylimino]-1-methylsulfanylethylidene]carbamic acid methyl ester

Product 1

HCID 1363663155-{(9-methoxy-3,4-dihydro-2H-benzo[b][1,4]dioxepin-7-yl)-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl]-2-(3-nitropyridin-2-yl)-2,4-dihydro-[1,2,4]triazol-3-oneYield 46.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

After adding 37.3 mg of (3-nitropyridin-2-yl)hydrazine and 37 μl of triethylamine to a solution of 109 mg of [2-(9-methoxy-3,4-dihydro-2H-benzo[b][1,4]dioxepin-7-yl)-2-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylimino]-1-methylsulfanylethylidene]carbamic acid methyl ester (Example (30c)) in 5 ml of DMF under a nitrogen atmosphere, the mixture was heated at 85° C. for 20 hours. The reaction mixture was concentrated under reduced pressure, the residue was dissolved in 20 ml of a methanol:THF=1:1 mixed solvent, 83 mg of sodium cyanotrihydroborate and 32 μl of acetic acid were added and the mixture was stirred at room temperature for 24 hours. After adding 100 ml of ethyl acetate and 50 ml of water, filtration was performed with celite. The aqueous layer was extracted with 50 ml of ethyl acetate, and then the organic layers were combined and dried over anhydrous magnesium sulfate, the desiccating agent was filtered off and the filtrate was concentrated under reduced pressure. The residue was purified by NAM silica gel column chromatography (methanol-ethyl acetate (1:40)) to give the title compound (59 mg) as a light yellow solid.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionthe residue was dissolved in 20 ml of a methanol
  3. additionTHF=1:1 mixed solvent, 83 mg of sodium cyanotrihydroborate and 32 μl of acetic acid were added
  4. additionAfter adding
  5. filtration100 ml of ethyl acetate and 50 ml of water, filtration
  6. extractionThe aqueous layer was extracted with 50 ml of ethyl acetate
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationthe desiccating agent was filtered off
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. customThe residue was purified by NAM silica gel column chromatography (methanol-ethyl acetate (1:40))

Sources & evidence

ORD record
ord-5f3b17128aec434d8915809115adafd9
Source dataset
uspto-grants-2010_10
Patent number
US07816522B2

Reaction notes

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