Hydrochloric Acid → HCID 178522243、化合物

HRID 660134ノート

反応式

HRID 660134 の反応式
[NH:1]([C:3](=[O:25])[C:4]([NH:6][C:7]1[CH:24]=[CH:23][C:10]([O:11][C@H:12]2[CH2:17][CH2:16][C@H:15]([C:18]([O:20]CC)=[O:19])[CH2:14][CH2:13]2)=[CH:9][CH:8]=1)=[O:5])[NH2:2].[F:26][CH:27]([F:38])[O:28][C:29]1[CH:34]=[CH:33][C:32]([N:35]=[C:36]=S)=[CH:31][CH:30]=1.CCN=C=NCCCN(C)C.[OH-].[Na+].Cl>CN(C=O)C.CO.C1COCC1.O>[F:26][CH:27]([F:38])[O:28][C:29]1[CH:30]=[CH:31][C:32]([NH:35][C:36]2[O:25][C:3]([C:4]([NH:6][C:7]3[CH:8]=[CH:9][C:10]([O:11][C@H:12]4[CH2:13][CH2:14][C@H:15]([C:18]([OH:20])=[O:19])[CH2:16][CH2:17]4)=[CH:23][CH:24]=3)=[O:5])=[N:1][N:2]=2)=[CH:33][CH:34]=1

参加物

10

反応物 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 20634951-(Difluoromethoxy)-4-isothiocyanatobenzeneHCID 178472470HCID 178472470、化合物2 回

生成物 1

HCID 178522243HCID 178522243、化合物収率 40.1%

試薬・触媒・溶媒 4

HCID 887Methanol溶媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
65 °C

実験手順

Ethyl trans-4-(4-{[hydrazino(oxo)acetyl]amino}phenoxy)cyclohexanecarboxylate (Intermediate 3, 698 mg, 2.00 mmol) was added in one portion to a stirred solution of 4-(difluoromethoxy)phenyl isothiocyanate (483 mg, 2.40 mmol) in DMF (10 mL) and the reaction mixture was stirred at 65° C. for 30 mins. EDCI (461 mg, 2.40 mmol) was added in one portion and the reaction mixture was heated to 85° C. for 3 h. The mixture was cooled to ambient temperature and water (15 mL) was added and the resulting suspension was filtered to provide a cream solid. The solid was taken up in a mixture of MeOH (8 mL) and THF (4 mL) and a 2N aqueous solution of NaOH (4 mL) was added in one portion and the reaction mixture was stirred at ambient temperature for 16 h. The reaction mixture was acidified by the addition of a 2M aqueous solution of HCl and the resulting precipitate was filtered, washed with water (10 mL) and dried under high vacuum to leave a solid. The solid was recrystallised from refluxing glacial acetic acid to give the title compound as a white solid (392 mg, 40%).

後処理

  1. temperaturethe reaction mixture was heated to 85° C. for 3 h
  2. temperatureThe mixture was cooled to ambient temperature
  3. filtrationthe resulting suspension was filtered
  4. customto provide a cream solid
  5. stirringthe reaction mixture was stirred at ambient temperature for 16 h
  6. filtrationthe resulting precipitate was filtered
  7. washwashed with water (10 mL)
  8. customdried under high vacuum
  9. customto leave a solid
  10. customThe solid was recrystallised
  11. temperaturefrom refluxing glacial acetic acid

出典と根拠

ORDレコード
ord-263b6328794344e499e16c292450fa79
出典データセット
uspto-grants-2011_12
特許番号
US08084478B2

反応ノート

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