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 1161562노트

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HRID 1161562 반응식
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]

참가 물질

5

반응물 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

생성물 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-one수율 45.1%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
85 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-5a40751f5996455991c95a2434114c54
출처 데이터셋
uspto-grants-2010_10
특허 번호
US07816522B2

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