Phosphorus oxide (P4O10) → 6-Bromo-4-(5-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3,4-oxadiazol-2-yl)-1-[(4-methylphenyl)sulfonyl]-1H-indazole

HRID 520550ノート

反応式

HRID 520550 の反応式
[Br:1][C:2]1[CH:3]=[C:4]([C:21]([NH:23][NH:24][C:25](=[O:35])[CH2:26][N:27]2[CH2:32][C@H:31]([CH3:33])[O:30][C@H:29]([CH3:34])[CH2:28]2)=O)[C:5]2[CH:6]=[N:7][N:8]([S:11]([C:14]3[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=3)(=[O:13])=[O:12])[C:9]=2[CH:10]=1.O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.[OH-].C([NH+](CC)CC)C>O1CCCC1>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[S:11]([C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=2)(=[O:12])=[O:13])=[C:4]([C:21]2[O:35][C:25]([CH2:26][N:27]3[CH2:32][C@H:31]([CH3:33])[O:30][C@H:29]([CH3:34])[CH2:28]3)=[N:24][N:23]=2)[CH:3]=1

参加物

5

反応物 3

HCID 14812Phosphorus oxide (P4O10)HCID 21903323Triethylammonium hydroxideHCID 666915176-Bromo-N'-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]acetyl}-1-[(4-methylphenyl)sulfonyl]-1H-indazole-4-carbohydrazide2 回

生成物 1

HCID 666957066-Bromo-4-(5-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3,4-oxadiazol-2-yl)-1-[(4-methylphenyl)sulfonyl]-1H-indazole収率 73.9%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
75 °C

実験手順

6-Bromo-N′-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]acetyl}-1-[(4-methylphenyl)sulfonyl]-1H-indazole-4-carbohydrazide (950 mg, 1.683 mmol) was dried over phosphorus pentoxide in a desicator overnight. 6-bromo-N′-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]acetyl}-1-[(4-methylphenyl)sulfonyl]-1H-indazole-4-carbohydrazide (950 mg, 1.683 mmol) and methoxycarbonylsulfamoyl)triethylammonium hydroxide (602 mg, 2.52 mmol) were suspended in anhydrous tetrahydrofuran (20 ml) and heated to 75° C. for 2 h. The solvent was removed in vacuo and the residue partitioned between dichloromethane (15 ml) and saturated sodium bicarbonate solution (15 ml). The layers were separated (hydrophobic frit), the aqueous washed with further dichloromethane (5 ml) and the combined organics concentrated in vacuo to give a yellow solid. This was purified by column chromatography, loading in dichloromethane onto a silica cartridge 50 g, using a 0-100% ethyl acetate-cyclohexane over 40 mins. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a white solid (680 mg).

後処理

  1. customThe solvent was removed in vacuo
  2. customthe residue partitioned between dichloromethane (15 ml) and saturated sodium bicarbonate solution (15 ml)
  3. customThe layers were separated (hydrophobic frit)
  4. washthe aqueous washed with further dichloromethane (5 ml)
  5. concentrationthe combined organics concentrated in vacuo
  6. customto give a yellow solid
  7. customThis was purified by column chromatography, loading in dichloromethane onto a silica cartridge 50 g
  8. customover 40 mins
  9. customevaporated in vacuo

出典と根拠

ORDレコード
ord-10672c6d9f094e9ab17beb6eb7a74786
出典データセット
uspto-grants-2016_05
特許番号
US09326987B2

反応ノート

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