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Ethyl Acetate → 4-(3-Tert-butyl-5-{3-[4-(pyridin-4-yloxy)phenyl]ureido}-pyrazol-1-yl)benzoic acid methyl ester

HRID 221880
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HRID 221880 반응식
[CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:9]=[CH:8][C:7]([N:10]2[C:14]([NH2:15])=[CH:13][C:12]([C:16]([CH3:19])([CH3:18])[CH3:17])=[N:11]2)=[CH:6][CH:5]=1.C1N=CN([C:26]([N:28]2C=N[CH:30]=[CH:29]2)=[O:27])C=1.[N:33]1[CH:38]=[CH:37][C:36]([O:39][C:40]2[CH:45]=CC(N)=[CH:42][CH:41]=2)=[CH:35][CH:34]=1.CCOC(C)=O>ClCCCl>[CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:5]=[CH:6][C:7]([N:10]2[C:14]([NH:15][C:26]([NH:28][C:29]3[CH:30]=[CH:45][C:40]([O:39][C:36]4[CH:37]=[CH:38][N:33]=[CH:34][CH:35]=4)=[CH:41][CH:42]=3)=[O:27])=[CH:13][C:12]([C:16]([CH3:17])([CH3:19])[CH3:18])=[N:11]2)=[CH:8][CH:9]=1
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참가 물질

6

반응물 4

HCID 8857Ethyl AcetateHCID 682631,1'-CarbonyldiimidazoleHCID 2973426methyl 4-(5-amino-3-tert-butyl-1H-pyrazol-1-yl)benzoateHCID 115645894-(Pyridin-4-yloxy)aniline

생성물 1

HCID 536301834-(3-Tert-butyl-5-{3-[4-(pyridin-4-yloxy)phenyl]ureido}-pyrazol-1-yl)benzoic acid methyl ester수율 68.4%

시약·촉매·용매 1

HCID 111,2-Dichloroethane용매2회

실험 절차

To a suspension of 4-(5-amino-3-tert-butyl-pyrazol-1-yl)benzoic acid methyl ester (1.89 g, 6.93 mmol) in anhydrous DCE (10 mL) was added CDI (1.24 g, 7.62 mmol), and the mixture was stirred at room temperature for 16 h. A suspension of 4-(pyridin-4-yloxy)phenylamine (1.29 g, 6.93 mmol; Dumas et al., U.S. pat. appl. US2002065296 (2002)) in DCE was then added, and the mixture was stirred at room temperature for 4 h. The reaction was diluted into EtOAc. The organic layer was washed with water and brine, dried over MgSO4, filtered, and concentrated at reduced pressure. The crude product was purified by MPLC (15% EtOAc/hexane) to give 2.3 g (68%) of the title compound as a white solid. 1H-NMR (acetone-d6) δ 8.64 (s, 1H), 8.44 (d, J=9.0 Hz, 2H), 8.12 (d, J=9.0 Hz, 2H), 8.01 (s, 1H), 7.61 (d, J=9.0 Hz, 2H), 7.81 (d, J=9.0 Hz, 2H), 7.09 (d, J=9.0 Hz, 2H), 6.86 (d, J=6.0 Hz, 2H), 6.48 (s, 1H), 3.91 (s, 3H), 1.34 (s, 9H); MS LC-MS [M+H]+=486, RT=2.50 min.

후처리

  1. additionwas then added
  2. stirringthe mixture was stirred at room temperature for 4 h
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated at reduced pressure
  7. customThe crude product was purified by MPLC (15% EtOAc/hexane)

출처 및 근거

ORD 기록
ord-3205fd7a3500433e95cce6fdc42d248e
출처 데이터셋
uspto-grants-2012_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08207166B2

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