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

反応式

HRID 609582 の反応式
[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

参加物

5

反応物 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-bromobenzenesulfonate2 回

生成物 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-methanesulfonate収率 13.7%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
80 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-ff3d1fb40ea24d85a6e21c6e0437136d
出典データセット
uspto-grants-1999_12
特許番号
US05998413

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