Azetidine → 2-Fluoro-4-(3-(1-(7-fluoroquinolin-2-YL)azetidin-3-YL)pyrazin-2-YL)-N-methylbenzamide

HRID 624524ノート

反応式

HRID 624524 の反応式
FC(F)(F)C(O)=O.FC(F)(F)C(O)=O.FC(F)(F)C(O)=O.[NH:22]1[CH2:25][CH:24]([C:26]2[C:27]([C:32]3[CH:41]=[CH:40][C:35]([C:36]([NH:38][CH3:39])=[O:37])=[C:34]([F:42])[CH:33]=3)=[N:28][CH:29]=[CH:30][N:31]=2)[CH2:23]1.C(=O)([O-])[O-].[K+].[K+].FC(F)(F)S(O[C:55]1[CH:64]=[CH:63][C:62]2[C:57](=[CH:58][C:59]([F:65])=[CH:60][CH:61]=2)[N:56]=1)(=O)=O.N1CCC1>O.CS(C)=O>[F:42][C:34]1[CH:33]=[C:32]([C:27]2[C:26]([CH:24]3[CH2:23][N:22]([C:55]4[CH:64]=[CH:63][C:62]5[C:57](=[CH:58][C:59]([F:65])=[CH:60][CH:61]=5)[N:56]=4)[CH2:25]3)=[N:31][CH:30]=[CH:29][N:28]=2)[CH:41]=[CH:40][C:35]=1[C:36]([NH:38][CH3:39])=[O:37]

参加物

7

反応物 4

HCID 10422AzetidineHCID 11430Potassium CarbonateHCID 866941337-Fluoroquinolin-2-yl trifluoromethanesulfonateHCID 867054064-(3-(Azetidin-3-YL)pyrazin-2-YL)-2-fluoro-N-methylbenzamide tris(2,2,2-trifluoroacetate)

生成物 1

HCID 726942252-Fluoro-4-(3-(1-(7-fluoroquinolin-2-YL)azetidin-3-YL)pyrazin-2-YL)-N-methylbenzamide収率 78%

試薬・触媒・溶媒 2

HCID 679Dimethyl Sulfoxide溶媒HCID 962Water溶媒

反応条件

温度
50 °C

実験手順

A mixture of 4-(3-(azetidin-3-yl)pyrazin-2-yl)-2-fluoro-N-methylbenzamide tris(2,2,2-trifluoroacetate) (0.953 g, 1.517 mmol), potassium carbonate (0.839 g, 6.070 mmol), 7-fluoroquinolin-2-yl trifluoromethanesulfonate (0.537 g, 1.821 mmol, prepared according to Step 3 of Example 2), and DMSO (10 mL) was stirred at 50° C. for 1 h. LCMS showed the product and no more azetidine starting material. The mixture was diluted with water and extracted with CH2Cl2 three times. The organic layer was dried over Na2SO4 and concentrated in vacuo. The crude was purified by silica gel chromatography: 40 g, 5-100% EtOAc-hexane. The impurity 2-hydroxyquinoline was further removed by trituration with CH2Cl2 and hexane twice. The product was obtained as a white solid (510 mg, 78%). 1H NMR (400 MHz, chloroFORM-d) δ ppm 3.09 (d, J=4.50 Hz, 3 H) 4.33-4.50 (m, 5 H) 6.56 (d, J=9.00 Hz, 1 H) 6.81 (d, J=7.04 Hz, 1 H) 6.98 (td, J=8.61, 2.54 Hz, 1 H) 7.31-7.45 (m, 3 H) 7.56 (dd, J=8.71, 6.36 Hz, 1 H) 7.84 (d, J=9.00 Hz, 1 H) 8.28 (t, J=8.02 Hz, 1 H) 8.57 (d, J=2.15 Hz, 1 H) 8.64 (d, J=2.35 Hz, 1 H). m/z=432 (M+1 ).

後処理

  1. extractionextracted with CH2Cl2 three times
  2. dry with materialThe organic layer was dried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customThe crude was purified by silica gel chromatography
  5. customThe impurity 2-hydroxyquinoline was further removed by trituration with CH2Cl2 and hexane twice

出典と根拠

ORDレコード
ord-43bc2685674a42e2835200e360db6156
出典データセット
uspto-grants-2016_04
特許番号
US09303028B2

反応ノート

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