4-(Pyridin-4-yloxy)aniline → 1-{5-tert-butyl-2-[3-(3-hydroxy-propoxy)-phenyl]-2H-pyrazol-3-yl}-3-[4-(pyridin-4-yloxy)-phenyl]-urea

HRID 1174864노트

반응식

HRID 1174864 반응식
C1(O[C:8](=[O:30])[NH:9][C:10]2[N:11]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([O:25][CH2:26][CH2:27][CH2:28][OH:29])[CH:20]=3)[N:12]=[C:13]([C:15]([CH3:18])([CH3:17])[CH3:16])[CH:14]=2)C=CC=CC=1.[N:31]1[CH:36]=[CH:35][C:34]([O:37][C:38]2[CH:43]=[CH:42][C:41]([NH2:44])=[CH:40][CH:39]=2)=[CH:33][CH:32]=1>C1COCC1>[C:15]([C:13]1[CH:14]=[C:10]([NH:9][C:8]([NH:44][C:41]2[CH:40]=[CH:39][C:38]([O:37][C:34]3[CH:35]=[CH:36][N:31]=[CH:32][CH:33]=3)=[CH:43][CH:42]=2)=[O:30])[N:11]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([O:25][CH2:26][CH2:27][CH2:28][OH:29])[CH:20]=2)[N:12]=1)([CH3:17])([CH3:18])[CH3:16]

참가 물질

4

반응물 2

HCID 115645894-(Pyridin-4-yloxy)anilineHCID 53630193{5-tert-butyl-2-[3-(3-hydroxy-propoxy)-phenyl]-2H-pyrazol-3-yl}-carbamic acid phenyl ester

생성물 1

HCID 115042801-{5-tert-butyl-2-[3-(3-hydroxy-propoxy)-phenyl]-2H-pyrazol-3-yl}-3-[4-(pyridin-4-yloxy)-phenyl]-urea

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
60 °C

실험 절차

To a solution of 3-[3-(5-amino-3-tert-butyl-pyrazol-1-yl)-phenoxy]-propan-1-ol (400 mg, 1.38 mmol) and phenyl chloroformate (324 mg, 2.07 mmol) in THF (14 mL) was added cesium carbonate (673 mg, 2.07 mmol). The mixture was stirred at room temperature for 4 h, additional phenyl chloroformate (108 mg, 0.69 mmol) was added, and then the mixture was stirred for an additional two hours. The reaction mixture was washed with saturated NaHCO3 (3×30 mL), water, brine, dried (Na2SO4), and evaporated at reduced pressure to give the crude carbamate intermediate {5-tert-butyl-2-[3-(3-hydroxy-propoxy)-phenyl]-2H-pyrazol-3-yl}-carbamic acid phenyl ester (500 mg). Step 2. To a solution of {5-tert-butyl-2-[3-(3-hydroxy-propoxy)-phenyl]-2H-pyrazol-3-yl}-carbamic acid phenyl ester (200 mg, 0.49 mmol) in THF was added 4-(pyridin-4-yloxy)-phenylamine (109 mg, 0.59 mmol). The reaction mixture was heated at 60° C. for 16 h. The reaction mixture was cooled to room temperature, concentrated at reduced pressure, and the residue was dissolved in DMF and methanol. The product was isolated by preparative HPLC, and the HPLC fraction containing the desired product was concentrated at reduced pressure and then partitioned between EtOAc (20 mL) and saturated aq Na2CO3 (10 mL). The organic layer was dried over Na2SO4 and evaporated to give 1-{5-tert-butyl-2-[3-(3-hydroxy-propoxy)-phenyl]-2H-pyrazol-3-yl}-3-[4-(pyridin-4-yloxy)-phenyl]-urea (51.3 mg, 21%). 1H-NMR (DMSO-d6) δ 7.50 (d, 2H), 7.10 (m, 5H), 6.90 (d, 2H), 6.70 (m, 3H), 6.40 (s, 1H), 4.0 (t, 2H), 3.60 (t, 3H), 1.80 (m, 2H), 1.30 (s, 9H); MS LC-MS [M+H]+=502.1, RT=2.36 min.

후처리

  1. temperatureThe reaction mixture was cooled to room temperature
  2. concentrationconcentrated at reduced pressure
  3. dissolutionthe residue was dissolved in DMF
  4. customThe product was isolated by preparative HPLC

출처 및 근거

ORD 기록
ord-d2e47b2d004a4cc3b43a7533115493a1
출처 데이터셋
uspto-grants-2010_11
특허 번호
US07838524B2

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