Sodium hydride → (+)-(S)-2,4-dihydro-4-[4-[4-(4-methoxyphenyl)-1-piperazinyl]-phenyl]-2-(1-methylpropyl)-3H-1,2,4-triazol-3-one (S)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptane-1-methanesulfonate

HRID 609582

반응식

HRID 609582 반응식
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][N:12]([C:15]3[CH:20]=[CH:19][C:18]([N:21]4[CH:25]=[N:24][NH:23][C:22]4=[O:26])=[CH:17][CH:16]=3)[CH2:11][CH2:10]2)=[CH:5][CH:4]=1.[H-].[Na+].[CH3:29][C@@H:30](O)[CH2:31]C.Br[C:35]1[CH:40]=C[C:38]([S:41]([O-:44])(=[O:43])=[O:42])=[CH:37][CH:36]=1>CN(C)C=O>[CH3:29][C:30]1([CH3:31])[CH:5]2[CH2:6][CH2:7][C@@:8]1([CH2:38][S:41]([OH:44])(=[O:43])=[O:42])[C:3](=[O:2])[CH2:4]2.[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:10][CH2:11][N:12]([C:15]3[CH:20]=[CH:19][C:18]([N:21]4[CH:25]=[N:24][N:23]([C@@H:35]([CH3:40])[CH2:36][CH3:37])[C:22]4=[O:26])=[CH:17][CH:16]=3)[CH2:13][CH2:14]2)=[CH:5][CH:4]=1

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 42465972,4-Dihydro-4-(4-(4-(4-methoxyphenyl)piperazin-1-yl)phenyl)-3H-1,2,4-triazol-3-oneHCID 131721473(R)-2-butanol 4-bromobenzenesulfonate2회

생성물 1

HCID 131721474(+)-(S)-2,4-dihydro-4-[4-[4-(4-methoxyphenyl)-1-piperazinyl]-phenyl]-2-(1-methylpropyl)-3H-1,2,4-triazol-3-one (S)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptane-1-methanesulfonate수율 13.7%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
80 °C

실험 절차

A mixture of 3.5 g of (2,4-dihydro-4-[4-[4-(4-methoxyphenyl)-1-piperazinyl]-phenyl]-3H-1,2,4-triazol-3-one, 0.6 g of a sodium hydride dispersion 50% and 100 ml of N,N-dimethylformamide was stirred for 3 hours at 80° C. After the addition of 3.5 g of (R)-2-butanol 4-bromobenzenesulfonate (ester) (intermediate (3)), stirring was continued for 6 hours at this temperature. After cooling, waster was added. The crystallized product was filtered off and taken up in trichloromethane. The undissolved part was filtered off. The remaining solution was dried and purified by column chromatography over silica gel using trichloromethane as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from 4-methyl-2-pentanone. The product was filtered off and converted into the (S)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptane-1-methanesulfonate salt in 2-propanone. The salt was filtered off and recrystallized from 1-butanol. The product was filtered off and dried, yielding 1.2 g (13.7%) of (+)-(S)-2,4-dihydro-4-[4-[4-(4-methoxyphenyl)-1-piperazinyl]-phenyl]-2-(1-methylpropyl)-3H-1,2,4-triazol-3-one (S)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptane-1-methanesulfonate (1:2); mp. 192.0° C.; [α]D20 =+28.41° (conc.=1% in ethanol) (interm. 5).

후처리

  1. stirringstirring
  2. waitwas continued for 6 hours at this temperature
  3. temperatureAfter cooling
  4. additionwaster was added
  5. filtrationThe crystallized product was filtered off
  6. filtrationThe undissolved part was filtered off
  7. customThe remaining solution was dried
  8. custompurified by column chromatography over silica gel
  9. customThe pure fractions were collected
  10. customthe eluent was evaporated
  11. customThe residue was crystallized from 4-methyl-2-pentanone
  12. filtrationThe product was filtered off
  13. filtrationThe salt was filtered off
  14. customrecrystallized from 1-butanol
  15. filtrationThe product was filtered off
  16. customdried

출처 및 근거

ORD 기록
ord-ff3d1fb40ea24d85a6e21c6e0437136d
출처 데이터셋
uspto-grants-1999_12
특허 번호
US05998413

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