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 1174864ノート

反応式

HRID 1174864 の反応式
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]

参加物

4

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
60 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-d2e47b2d004a4cc3b43a7533115493a1
出典データセット
uspto-grants-2010_11
特許番号
US07838524B2

反応ノート

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