Hydrochloric Acid → 6-(1H-Indol-4-yl)-4-{5-[(methylsulfonyl)methyl]-1,3,4-oxadiazol-2-yl}-1H-indazole

HRID 38877

反応式

HRID 38877 の反応式
Cl[CH2:2][C:3]1[O:7][C:6]([C:8]2[CH:16]=[C:15]([C:17]3[CH:25]=[CH:24][CH:23]=[C:22]4[C:18]=3[CH:19]=[CH:20][NH:21]4)[CH:14]=[C:13]3[C:9]=2[CH:10]=[N:11][N:12]3S(C2C=CC=CC=2)(=O)=O)=[N:5][N:4]=1.[CH3:35][S:36]([O-:38])=[O:37].[Na+].[OH-].[Na+].Cl>C(O)C.C(O)(C)C>[NH:21]1[C:22]2[C:18](=[C:17]([C:15]3[CH:14]=[C:13]4[C:9]([CH:10]=[N:11][NH:12]4)=[C:8]([C:6]4[O:7][C:3]([CH2:2][S:36]([CH3:35])(=[O:38])=[O:37])=[N:4][N:5]=4)[CH:16]=3)[CH:25]=[CH:24][CH:23]=2)[CH:19]=[CH:20]1

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 2733271Sodium methanesulfinate2 回HCID 667769544-[5-(Chloromethyl)-1,3,4-oxadiazol-2-yl]-6-(1H-indol-4-yl)-1-(phenylsulfonyl)-1H-indazole

生成物 1

HCID 666937816-(1H-Indol-4-yl)-4-{5-[(methylsulfonyl)methyl]-1,3,4-oxadiazol-2-yl}-1H-indazole収率 12.5%

試薬・触媒・溶媒 2

HCID 702Ethanol溶媒HCID 3776Isopropanol溶媒

反応条件

温度
150 °C

実験手順

4-[5-(Chloromethyl)-1,3,4-oxadiazol-2-yl]-6-(1H-indol-4-yl)-1-(phenylsulfonyl)-1H-indazole (50 mg, 0.102 mmol) and sodium methanesulfinate (10.42 mg, 0.102 mmol) in ethanol (0.8 ml) were heated under microwave irradiation to 100° C. for 30 mins then 150° C. for 30 min, followed by 150° C. for a further 30 mins. Additional sodium methanesulfinate (10.42 mg, 0.102 mmol) was added and the reaction heated to 150° C. for a further 30 mins. The solvent was removed and the resultant beige solid treated with isopropanol (1 ml) and 2M aqueous sodium hydroxide (1.003 ml, 2.006 mmol) and stirred at 20° C. for 20 h. The mixture was neutralised with 2M aqueous hydrogen chloride, evaporated to dryness and azeotroped with isopropanol (2 ml). The residue was partitioned between dichloromethane (5 ml) and water (5 ml) and shaken vigorously. The aqueous phase was pipetted off, then the heterogeneous solution was treated with methanol (5 ml), absorbed onto Florisil and the solvents removed. The Florisil was placed on top of a silica cartridge (10 g) and eluted with 0-3% methanol/dichloromethane. Appropriate fractions were combined and concentrated to give a beige solid, 16 mg. Further purification by Mass Directed Automated Preparative HPLC afforded the title compound as a white solid (5 mg).

後処理

  1. waitfollowed by 150° C. for a further 30 mins
  2. customThe solvent was removed
  3. customevaporated to dryness
  4. customazeotroped with isopropanol (2 ml)
  5. customThe residue was partitioned between dichloromethane (5 ml) and water (5 ml)
  6. stirringshaken vigorously
  7. additionthe heterogeneous solution was treated with methanol (5 ml)
  8. customabsorbed onto Florisil
  9. customthe solvents removed
  10. washeluted with 0-3% methanol/dichloromethane
  11. concentrationconcentrated
  12. customto give a beige solid, 16 mg
  13. customFurther purification by Mass Directed Automated Preparative HPLC

出典と根拠

ORDレコード
ord-6361ad6759fb492eac10bac7ce879ccf
出典データセット
uspto-grants-2013_09
特許番号
US08524751B2

関連ノート

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