Triethylamine → 3-(3-{{3-[2-(t-Butyldimethylsilanyloxy)ethoxy]-2-fluoro-5-methoxyphenyl}-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-5-oxo-4,5-dihydro-1H-[1,2,4]triazol-1-yl)-1H-pyrazin-2-one

HRID 1161562Notes

Reaction equation

HRID 1161562 reaction equation
Cl.[NH:2]([C:4]1[C:5](=[O:10])[NH:6][CH:7]=[CH:8][N:9]=1)[NH2:3].C(N(CC)CC)C.C[O:19][C:20](=O)[N:21]=[C:22](SC)[C:23]([C:37]1[CH:42]=[C:41]([O:43][CH3:44])[CH:40]=[C:39]([O:45][CH2:46][CH2:47][O:48][Si:49]([C:52]([CH3:55])([CH3:54])[CH3:53])([CH3:51])[CH3:50])[C:38]=1[F:56])=[N:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]2[N:35]=[C:34]([CH3:36])[O:33][N:32]=2)=[CH:27][CH:26]=1>CN(C=O)C>[Si:49]([O:48][CH2:47][CH2:46][O:45][C:39]1[C:38]([F:56])=[C:37]([CH:23]([NH:24][C:25]2[CH:26]=[CH:27][C:28]([C:31]3[N:35]=[C:34]([CH3:36])[O:33][N:32]=3)=[CH:29][CH:30]=2)[C:22]2[NH:21][C:20](=[O:19])[N:2]([C:4]3[C:5](=[O:10])[NH:6][CH:7]=[CH:8][N:9]=3)[N:3]=2)[CH:42]=[C:41]([O:43][CH3:44])[CH:40]=1)([C:52]([CH3:55])([CH3:54])[CH3:53])([CH3:51])[CH3:50]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 675039343-Hydrazinylpyrazin-2(1H)-one hydrochlorideHCID 72312769(2-{3-[2-(t-Butyldimethylsilanyloxy)ethoxy]-2-fluoro-5-methoxyphenyl}-2-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylimino]-1-methylsulfanylethylidene)carbamic acid methyl ester

Product 1

HCID 1359820683-(3-{{3-[2-(t-Butyldimethylsilanyloxy)ethoxy]-2-fluoro-5-methoxyphenyl}-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-5-oxo-4,5-dihydro-1H-[1,2,4]triazol-1-yl)-1H-pyrazin-2-oneYield 45.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

3-Hydrazino-1H-pyrazin-2-one hydrochloride (24 mg) and triethylamine (0.033 ml) were added to 3 ml of a DMF solution containing 70 mg of (2-{3-[2-(t-butyldimethylsilanyloxy)ethoxy]-2-fluoro-5-methoxyphenyl}-2-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylimino]-1-methylsulfanylethylidene)carbamic acid methyl ester (Example (200a)). The resulting mixture was stirred at 85° C. for 16 hours and then concentrated under reduced pressure. The residue was dissolved in 5 ml of methanol, and 58 mg of sodium cyanotrihydroborate and 0.056 ml of acetic acid were further added thereto. The mixture was stirred at room temperature for 15 hours. To this reaction mixture, 40 ml of ethyl acetate and 20 ml of water were added. The organic layer was washed with 20 ml of water and then with 20 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 (34 mg).

Workup

  1. concentrationconcentrated under reduced pressure
  2. dissolutionThe residue was dissolved in 5 ml of methanol
  3. addition58 mg of sodium cyanotrihydroborate and 0.056 ml of acetic acid were further added
  4. stirringThe mixture was stirred at room temperature for 15 hours
  5. additionTo this reaction mixture, 40 ml of ethyl acetate and 20 ml of water were added
  6. washThe organic layer was washed with 20 ml of water
  7. dry with materialwith 20 ml of saturated brine and then dried over anhydrous magnesium sulfate
  8. customThe desiccating agent was removed by filtration
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. customThe residue was purified by NAM silica gel column chromatography (methanol-ethyl acetate)

Sources & evidence

ORD record
ord-5a40751f5996455991c95a2434114c54
Source dataset
uspto-grants-2010_10
Patent number
US07816522B2

Reaction notes

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