Potassium Carbonate → tert-butyl 2-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenoxy)ethylcarbamate

HRID 1958663

반응식

HRID 1958663 반응식
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[NH:10][C:11]([C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([CH3:30])[N:25]=3)=[C:12]([C:14]3[CH:15]=[C:16]4[C:21](=[CH:22][CH:23]=3)[N:20]=[CH:19][CH:18]=[CH:17]4)[N:13]=2)=[CH:4][C:3]=1[OH:31].Br[CH2:33][CH2:34][NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39].C([O-])([O-])=O.[K+].[K+]>CC(C)=O.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[NH:10][C:11]([C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([CH3:30])[N:25]=3)=[C:12]([C:14]3[CH:15]=[C:16]4[C:21](=[CH:22][CH:23]=3)[N:20]=[CH:19][CH:18]=[CH:17]4)[N:13]=2)=[CH:4][C:3]=1[O:31][CH2:33][CH2:34][NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39]

참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 4103526tert-Butyl N-(2-bromoethyl)carbamateHCID 445460652-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenol

생성물 1

HCID 68539825tert-butyl 2-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenoxy)ethylcarbamate수율 91.4%

시약·촉매·용매 2

HCID 180Acetone용매HCID 962Water용매

반응 조건

온도
60 °C

실험 절차

To a stirred solution of 2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenol (Example 81) (100 mg, 0.244 mmol) in acetone (5 mL) were added tert-butyl 2-bromoethylcarbamate (109 mg, 0.488 mmol) and K2CO3 (67 mg, 0.488 mmol) and the mixture was stirred at 60° C. for 20 hours. The reaction mixture was cooled to room temperature, diluted with H2O (20 mL), and extracted with CH2Cl2 (5 mL, 3 times). The organic layer was dried over Na2SO4, filtered, and evaporated under reduced pressure. The residue was purified by MPLC on NH silica gel (MeOH:CH2Cl2=1:50 (v/v)) to give tert-butyl 2-(2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenoxy)ethylcarbamate (123.5 mg, 91%). This compound was dissolved in CH2Cl2 (5 mL), and p-anisole (224 uL, 2.23 mmol) and trifluoroacetic acid (1 mL) were added. The mixture was stirred for 1 hour, then concentrated, diluted with H2O (10 mL), and neutralized by addition of aqueous NH4OH solution to pH 7˜8. The aqueous solution was saturated with NH4Cl solid, extracted with CH2Cl2 (5 mL, 3 times), and then the organic layer was dried over Na2SO4, filtered, and evaporated under reduced pressure. The residue was purified by MPLC on NH silica gel (MeOH:CH2Cl2=3:100 (v/v)) to afford the title compound (70.2 mg, 69%). 1H NMR (300 MHz, CDCl3) δ 2.50 (3H, s), 3.09 (2H, t), 4.04 (2H, t), 4.16 (2H, s), 6.85-6.90 (1H, m), 6.95-7.07 (3H, m), 7.24 (1H, s), 7.36 (1H, d), 7.41 (1H, dd), 7.97 (1H, dd), 8.09-8.18 (3H, m), 8.92 (1H, dd), 10.40 (1H, bs). MS (ESI) m/z 454 (MH+).

후처리

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionextracted with CH2Cl2 (5 mL, 3 times)
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. customevaporated under reduced pressure
  6. customThe residue was purified by MPLC on NH silica gel (MeOH:CH2Cl2=1:50 (v/v))

출처 및 근거

ORD 기록
ord-277c7877d2c34e258db9f48817fde4a9
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08410146B2

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