Potassium Carbonate → 6-(2-(4-fluoro-3-(2-(pyrrolidin-1-yl)ethoxy)benzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline

HRID 1958659

반응식

HRID 1958659 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].Cl.Cl[CH2:34][CH2:35][N:36]1[CH2:40][CH2:39][CH2:38][CH2:37]1.C([O-])([O-])=O.[K+].[K+]>CC(C)=O.CN(C=O)C.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][CH2:34][CH2:35][N:36]1[CH2:40][CH2:39][CH2:38][CH2:37]1

참가 물질

7

반응물 3

HCID 11430Potassium CarbonateHCID 816681-(2-Chloroethyl)pyrrolidine hydrochlorideHCID 445460652-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)phenol

생성물 1

HCID 445460666-(2-(4-fluoro-3-(2-(pyrrolidin-1-yl)ethoxy)benzyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoline수율 53.2%

시약·촉매·용매 3

HCID 180Acetone용매HCID 962Water용매HCID 6228Dimethylformamide용매

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) (80 mg, 0.195 mmol) in acetone (6 mL) and DMF (3 mL) were added 1-(2-chloroethyl)pyrrolidine hydrochloride (50 mg, 0.292 mmol) and K2CO3 (81 mg, 0.585 mmol). The mixture was stirred at 60° C. for 6 hours, cooled to room temperature, and diluted with H2O (10 mL). The mixture was extracted with CH2Cl2 (25 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=1:50 (v/v) to 1:20 (v/v)) to afford the title compound (52.7 mg, 53%). 1H NMR (300 MHz, CDCl3) δ 1.78 (4H, pentet), 2.51 (3H, s), 2.63 (4, td), 2.93 (2H, t), 4.16 (2H, s), 7.18 (2H, t), 6.85-6.90 (1H, m), 6.94-7.07 (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), 10.01 (1H, bs). MS (ESI) m/z 508 (MH+).

후처리

  1. temperaturecooled to room temperature
  2. extractionThe mixture was extracted with CH2Cl2 (25 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) to 1:20 (v/v))

출처 및 근거

ORD 기록
ord-571fb05e4ef9481093446ab8e45e9c08
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08410146B2

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