Thionyl Chloride → 6-Bromo-N'-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]acetyl}-1-[(4-methylphenyl)sulfonyl]-1H-indazole-4-carbohydrazide

HRID 520549ノート

反応式

HRID 520549 の反応式
[Br:1][C:2]1[CH:3]=[C:4]([C:21](O)=[O:22])[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.S(Cl)(Cl)=O.[CH3:28][C@H:29]1[O:34][C@@H:33]([CH3:35])[CH2:32][N:31]([CH2:36][C:37]([NH:39][NH2:40])=[O:38])[CH2:30]1.CCN(C(C)C)C(C)C>O1CCCC1>[Br:1][C:2]1[CH:3]=[C:4]([C:21]([NH:40][NH:39][C:37](=[O:38])[CH2:36][N:31]2[CH2:32][C@H:33]([CH3:35])[O:34][C@H:29]([CH3:28])[CH2:30]2)=[O:22])[C:5]2[CH:6]=[N:7][N:8]([S:11]([C:14]3[CH:15]=[CH:16][C:17]([CH3:20])=[CH:18][CH:19]=3)(=[O:12])=[O:13])[C:9]=2[CH:10]=1

参加物

6

反応物 4

HCID 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 304034132-[(2R,6S)-2,6-Dimethyl-4-morpholinyl]acetohydrazideHCID 666917216-Bromo-1-[(4-methylphenyl)sulfonyl]-1H-indazole-4-carboxylic acid

生成物 1

HCID 666915176-Bromo-N'-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]acetyl}-1-[(4-methylphenyl)sulfonyl]-1H-indazole-4-carbohydrazide収率 44.3%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
100 °C

実験手順

6-Bromo-1-[(4-methylphenyl)sulfonyl]-1H-indazole-4-carboxylic acid (1.5 g, 3.80 mmol) was suspended in thionyl chloride (8.31 ml, 114 mmol) and heated to 100° C. for 30 mins. The thionyl chloride was removed in vacuo and excess aziotroped with dry diethyl ether to give a yellow solid. This was dissolved in dry tetrahydrofuran (40 ml) and 2-[(2R,6S)-2,6-dimethyl-4-morpholinyl]acetohydrazide (1.066 g, 5.69 mmol) and DIPEA (2.65 ml, 15.18 mmol) added. The reaction mixture was heated to 60° C. for 20 mins. The solvent was removed in vacuo and the residue partitioned between dichloromethane (50 ml) and water (50 ml). The layers were separated and the organic concentrated in vacuo to give a yellow foam. This was purified by column chromatography, loading in dichloromethane onto a silica cartridge (50 g), eluting with 0-100% ethyl acetate-cyclohexane over 30 mins. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a yellow solid (950 mg).

後処理

  1. customThe thionyl chloride was removed in vacuo and excess aziotroped with dry diethyl ether
  2. customto give a yellow solid
  3. temperatureThe reaction mixture was heated to 60° C. for 20 mins
  4. customThe solvent was removed in vacuo
  5. customthe residue partitioned between dichloromethane (50 ml) and water (50 ml)
  6. customThe layers were separated
  7. concentrationthe organic concentrated in vacuo
  8. customto give a yellow foam
  9. customThis was purified by column chromatography, loading in dichloromethane onto a silica cartridge (50 g)
  10. washeluting with 0-100% ethyl acetate-cyclohexane over 30 mins
  11. customevaporated in vacuo

出典と根拠

ORDレコード
ord-bdce572f03044fe28d52346a1561441a
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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