Ammonium Hydroxide → 2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenol

HRID 1958658

反応式

HRID 1958658 の反応式
[F:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][C:7]2[NH:8][C:9]([C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([CH3:28])[N:23]=3)=[C:10]([C:12]3[CH:13]=[C:14]4[C:19](=[CH:20][CH:21]=3)[N:18]=[CH:17][CH:16]=[CH:15]4)[N:11]=2)=[CH:4][C:3]=1[O:31]C.Cl.N1C=CC=CC=1.[NH4+].[OH-]>O>[F:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][C:7]2[NH:8][C:9]([C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([CH3:28])[N:23]=3)=[C:10]([C:12]3[CH:13]=[C:14]4[C:19](=[CH:20][CH:21]=3)[N:18]=[CH:17][CH:16]=[CH:15]4)[N:11]=2)=[CH:4][C:3]=1[OH:31]

参加物

5

反応物 3

HCID 14923Ammonium HydroxideHCID 10176127Pyridinium chlorideHCID 445458706-(2-(4-fluoro-3-methoxybenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline

生成物 1

HCID 445460652-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenol収率 69%

試薬・触媒・溶媒 1

HCID 962Water溶媒

反応条件

温度
190 °C

実験手順

A mixture of 6-(2-(4-fluoro-3-methoxybenzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline (Example 80, prepared according to the method described in US 2008/0319012 A1) (948 mg, 2.23 mmol) and pyridine hydrochloride (95 g) was stirred at 190° C. for 80 min. Then the hot reaction mixture was poured into H2O (60 mL) and added NH4OH solution to pH 5. The aqueous solution was extracted with CH2Cl2 (30 mL, 7 times) and then the organic layer was dried over MgSO4, filtered, and evaporated under reduced pressure. The residue was purified by MPLC (MeOH:CH2Cl2=1:30 (v/v) to 1:15 (v/v)) to afford the solid, which was recrystallized from CH2Cl2/Et2O to give the title compound (635 mg, 69%). 1H NMR (300 MHz, CDCl3) δ 2.34 (3H, s), 3.95 (2H, s), 6.50 (1H, d), 6.56-6.57 (1H, m), 6.79 (1H, dd), 6.91 (1H, d), 7.25-7.33 (2H, m), 7.78 (1H, m), 7.91-7.97 (2H, m), 8.03 (1H, s), 8.81 (1H, d), 10.80 (1H, bs), 11.48 (1H, bs). MS (ESI) m/z 411 (MH+).

後処理

  1. customprepared
  2. extractionThe aqueous solution was extracted with CH2Cl2 (30 mL, 7 times)
  3. dry with materialthe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. customevaporated under reduced pressure
  6. customThe residue was purified by MPLC (MeOH:CH2Cl2=1:30 (v/v) to 1:15 (v/v))
  7. customto afford the solid, which
  8. customwas recrystallized from CH2Cl2/Et2O

出典と根拠

ORDレコード
ord-5ccf97d2471a4c128d600e93f5450140
出典データセット
uspto-grants-2013_04
特許番号
US08410146B2

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