Hydrochloric Acid → 1-(2-Fluoro-phenyl)-3-(piperidin-4-yloxy)-1h-indazole hydrochloride

HRID 1723855

反応式

HRID 1723855 の反応式
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[N:17]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[F:30])[N:16]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.[ClH:31]>C(OCC)(=O)C.O1CCOCC1>[ClH:31].[F:30][C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=1[N:17]1[C:18]2[C:23](=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:15]([O:14][CH:11]2[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]2)=[N:16]1

参加物

5

反応物 2

HCID 313Hydrochloric AcidHCID 685310084-[1-(2-Fluoro-phenyl)-1h-indazol-3-yloxy]-piperidine-1-carboxylic acid tert-butyl ester

生成物 1

HCID 574205491-(2-Fluoro-phenyl)-3-(piperidin-4-yloxy)-1h-indazole hydrochloride収率 55%

試薬・触媒・溶媒 2

HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

実験手順

To a stirred solution of 187 g (0.456 mole) of 4-[1-(2-fluoro-phenyl)-1H-indazol-3-yloxy]-piperidine-1-carboxylic acid tert-butyl ester in 600 mL of ethyl acetate was added 300 mL of 4M hydrogen chloride in dioxane dropwise over a 30 minute period. The temperature rose to 24° C. from 21° C. during the addition. When the addition was complete, gas evolution was observed and the temperature rose to 28° C. A cold water bath was used to lower the temperature to 18° C. After stirring for approximately 40 min, a solid began separating. Stirring was continued at 18-20° C. for 3 hours and then at −10° C. (ice-acetone bath) for 1 hour. The solid was collected by filtration, rinsed with 60 mL of ethyl acetate and pressed dry under suction. Further drying in vacuo at 30° C. for 16 hours afforded 87.3 g (55%) of product. The combined filtrate and washing was concentrated in vacuo to near dryness. The residue was taken up in 250 mL of ethyl acetate and the suspension was stirred at −10° C. for 2 hours. The solid was collected by filtration, rinsed with 30 mL of ethyl acetate and pressed dry under suction. Further drying in vacuo at 30° C. for 16 hours provided an additional 23.2 g (15%) of product. Total yield=110.5 g (70%). 1H NMR (CD3OD) δ ppm: 7.7 (d, 1H), 7.6 (t, 1H), 7.5-7.6 (m, 2H), 7.3-7.5 (m, 2H), 7.25 (m, 1H), 7.2 (t, 1H), 5.2 (m, 1H), 3.4-3.5 (m, 2H), 3.2-3.3 (m, 2H), 2.3-2.4 (m, 2H), 2.2-2.3 (m, 2H).

後処理

  1. additionThe temperature rose to 24° C. from 21° C. during the addition
  2. additionWhen the addition
  3. customrose to 28° C
  4. customA cold water bath was used
  5. customto 18° C
  6. customa solid began separating
  7. stirringStirring
  8. waitwas continued at 18-20° C. for 3 hours
  9. waitat −10° C. (ice-acetone bath) for 1 hour
  10. filtrationThe solid was collected by filtration
  11. washrinsed with 60 mL of ethyl acetate
  12. custompressed dry under suction
  13. customFurther drying in vacuo at 30° C. for 16 hours

出典と根拠

ORDレコード
ord-5cfef87baebc4395b5712709a9373e4f
出典データセット
uspto-grants-2009_02
特許番号
US07485636B2

関連ノート

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