Hydrazine hydrate (1:1) → 1-(1-(Cyano(4-(trifluoromethoxy)phenyl)methyl)piperidin-4-yloxy)-3-(4-fluorophenyl)urea

HRID 1895944노트

반응식

HRID 1895944 반응식
O.NN.O=C1C2C(=CC=CC=2)[C:7](=[O:14])[N:6]1[O:15][CH:16]1[CH2:21][CH2:20][N:19]([CH:22]([C:25]2[CH:30]=[CH:29][C:28]([O:31][C:32]([F:35])([F:34])[F:33])=[CH:27][CH:26]=2)[C:23]#[N:24])[CH2:18][CH2:17]1.[F:36][C:37]1[CH:42]=[CH:41][C:40]([N:43]=C=O)=[CH:39][CH:38]=1>C(Cl)Cl>[C:23]([CH:22]([C:25]1[CH:26]=[CH:27][C:28]([O:31][C:32]([F:35])([F:33])[F:34])=[CH:29][CH:30]=1)[N:19]1[CH2:20][CH2:21][CH:16]([O:15][NH:6][C:7]([NH:43][C:40]2[CH:41]=[CH:42][C:37]([F:36])=[CH:38][CH:39]=2)=[O:14])[CH2:17][CH2:18]1)#[N:24]

참가 물질

5

반응물 3

HCID 24654Hydrazine hydrate (1:1)HCID 709554-Fluorophenyl isocyanateHCID 671184582-(4-(1,3-Dioxoisoindolin-2-yloxy)piperidin-1-yl)-2-(4-(trifluoromethoxy)phenyl)acetonitrile

생성물 1

HCID 866527401-(1-(Cyano(4-(trifluoromethoxy)phenyl)methyl)piperidin-4-yloxy)-3-(4-fluorophenyl)urea수율 121.6%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

Hydrazine monohydrate (0.063 ml, 1.303 mmol) was added to a solution of 2-(4-(1,3-dioxoisoindolin-2-yloxy)piperidin-1-yl)-2-(4-(trifluoromethoxy)phenyl)acetonitrile (258 mg, 0.434 mmol) in CH2Cl2 (5 ml) and the whole was stirred at room temperature for 16 hours. The resulting solid was filtered off and the filtrate was concentrated in vacuo. The residue was dissolved in tetrahydrofuran (5 ml), treated with 4-fluorophenyl isocyanate (0.023 ml, 0.200 mmol) and stirred at room temperature for 14 hours. The reaction mixture was concentrated in vauo and the residue was purified by column chromatography (ethyl acetate/hexane: 50/50 to 0/100) and the resulting solid was triturated with ethyl acetate/hexane to give 1-(1-(cyano(4-(trifluoromethoxy)phenyl)methyl)piperidin-4-yloxy)-3-(4-fluorophenyl)urea (110 mg, 56%) as a white solid: LCMS: 442 [M+1]+. 1H NMR (DMSO-d6) δ: 1.67 (m, 1H), 1.81 (m, 1H), 1.94 (m, 2H), 2.33 (m, 2H), 2.58 (m, 1H), 2.88 (m, 1H), 3.76 (m, 1H), 5.47 (s, 1H), 7.10 (m, 2H), 7.46-7.60 (m, 6H), 8.62 (s, 1H), 9.43 (s, 1H).

후처리

  1. filtrationThe resulting solid was filtered off
  2. concentrationthe filtrate was concentrated in vacuo
  3. dissolutionThe residue was dissolved in tetrahydrofuran (5 ml)
  4. stirringstirred at room temperature for 14 hours
  5. concentrationThe reaction mixture was concentrated in vauo
  6. customthe residue was purified by column chromatography (ethyl acetate/hexane: 50/50 to 0/100)
  7. customthe resulting solid was triturated with ethyl acetate/hexane

출처 및 근거

ORD 기록
ord-428d2c8307964228889cd7075521af19
출처 데이터셋
uspto-grants-2013_08
특허 번호
US08518934B2

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