Triethylamine → 5-{(5-Fluoro-8-methoxychroman-6-yl)-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-2-pyrimidin-2-yl-2,4-dihydro-[1,2,4]triazol-3-one

HRID 1698693Notes

Reaction equation

HRID 1698693 reaction equation
[NH:1]([C:3]1[N:8]=[CH:7][CH:6]=[CH:5][N:4]=1)[NH2:2].C(N(CC)CC)C.C[O:17][C:18](=O)[N:19]=[C:20](SC)[C:21]([C:35]1[C:36]([F:47])=[C:37]2[C:42](=[C:43]([O:45][CH3:46])[CH:44]=1)[O:41][CH2:40][CH2:39][CH2:38]2)=[N:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]2[N:33]=[C:32]([CH3:34])[O:31][N:30]=2)=[CH:25][CH:24]=1>CN(C=O)C>[F:47][C:36]1[C:35]([CH:21]([NH:22][C:23]2[CH:28]=[CH:27][C:26]([C:29]3[N:33]=[C:32]([CH3:34])[O:31][N:30]=3)=[CH:25][CH:24]=2)[C:20]2[NH:19][C:18](=[O:17])[N:1]([C:3]3[N:8]=[CH:7][CH:6]=[CH:5][N:4]=3)[N:2]=2)=[CH:44][C:43]([O:45][CH3:46])=[C:42]2[C:37]=1[CH2:38][CH2:39][CH2:40][O:41]2

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 3465582-HydrazinylpyrimidineHCID 72312734[2-(5-Fluoro-8-methoxychroman-6-yl)-2-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylimino]-1-methylsulfanylethylidene]carbamic acid methyl ester

Product 1

HCID 1363664735-{(5-Fluoro-8-methoxychroman-6-yl)-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-2-pyrimidin-2-yl-2,4-dihydro-[1,2,4]triazol-3-oneYield 74%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

After adding 23 mg of 2-hydrazinopyrimidine and 35 μl of triethylamine to a solution of 113 mg of [2-(5-fluoro-8-methoxychroman-6-yl)-2-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylimino]-1-methylsulfanylethylidene]carbamic acid methyl ester in 2 ml of DMF, the mixture was stirred overnight at 85° C. under a nitrogen atmosphere. The reaction mixture was concentrated, and the residue was dissolved in 5 ml of methanol and 0.5 ml of acetic acid. After adding 100 mg of sodium cyanotrihydroborate to the reaction mixture it was stirred at room temperature for 1 hour. Water was added to the reaction mixture and extraction was performed with ethyl acetate. The organic layer was 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) to give 5-{(5-fluoro-8-methoxychroman-6-yl)-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-2-pyrimidin-2-yl-2,4-dihydro-[1,2,4]triazol-3-one (82 mg) as a light brown solid.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionthe residue was dissolved in 5 ml of methanol
  3. additionAfter adding 100 mg of sodium cyanotrihydroborate to the reaction mixture it
  4. stirringwas stirred at room temperature for 1 hour
  5. additionWater was added to the reaction mixture and extraction
  6. dry with materialThe organic layer was dried 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 NAM silica gel column chromatography (methanol-ethyl acetate)

Sources & evidence

ORD record
ord-67e570aabc41446b97ae92e5b34e3581
Source dataset
uspto-grants-2012_04
Patent number
US08163787B2

Reaction notes

Loading…