Phosphorus oxychloride → HCID 71534484、化合物

HRID 1523734ノート

反応式

HRID 1523734 の反応式
[CH:1]([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([C:13]([NH:15][NH2:16])=[O:14])=[N:5]1)([CH3:3])[CH3:2].Cl.[CH:18]1([N:22]2[CH2:27][CH2:26][CH:25]([CH2:28][C:29](O)=O)[CH2:24][CH2:23]2)[CH2:21][CH2:20][CH2:19]1.P(Cl)(Cl)(Cl)=O>>[CH:18]1([N:22]2[CH2:23][CH2:24][CH:25]([CH2:28][C:29]3[O:14][C:13]([C:6]4[C:7]5[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=5)[N:4]([CH:1]([CH3:3])[CH3:2])[N:5]=4)=[N:15][N:16]=3)[CH2:26][CH2:27]2)[CH2:19][CH2:20][CH2:21]1

参加物

4

反応物 3

HCID 24813Phosphorus oxychlorideHCID 86724908HCID 86724908、化合物HCID 86724919HCID 86724919、化合物

生成物 1

HCID 71534484HCID 71534484、化合物収率 30%

反応条件

温度
0 °C

実験手順

To the mixture of 1-isopropyl-1H-indazole-3-carboxylic acid hydrazide (120 mg, 0.55 mmol) and (1-cyclobutyl piperidin-4-yl) acetic acid hydrochloride (147 mg, 0.74 mmol, obtained in preparation 6) cooled at 0° C., was added phosphoryl chloride (1.5 mL). The reaction temperature was gradually raised to 100° C. and stirred was 2 hours. Upon completion of the reaction, it was cooled to 0° C. and triturated with hexanes (3×25 mL). The crude product was cooled to 0° C., basified with aqueous sodium hydroxide solution and extracted with 5% methanol in dichloromethane. The combined organic layer was dried over anhydrous sodium sulphate and the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography to obtain 3-[5-(1-cyclobutyl piperidin-4-yl methyl)-[1,3,4]oxadiazol-2-yl]-1-isopropyl-1H-indazole (62 mg)

後処理

  1. temperatureThe reaction temperature was gradually raised to 100° C.
  2. customUpon completion of the reaction, it
  3. temperaturewas cooled to 0° C.
  4. customtriturated with hexanes (3×25 mL)
  5. temperatureThe crude product was cooled to 0° C.
  6. extractionextracted with 5% methanol in dichloromethane
  7. dry with materialThe combined organic layer was dried over anhydrous sodium sulphate
  8. customthe solvent was removed under reduced pressure
  9. customThe crude product was purified by silica gel column chromatography

出典と根拠

ORDレコード
ord-8a8c841d850245b3a9871b4159ef359a
出典データセット
uspto-grants-2015_07
特許番号
US09079894B2

反応ノート

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