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Potassium Carbonate → 4-(3-(1-(7-Chloroquinazolin-2-YL)azetidin-3-YL)pyrazin-2-YL)-2-fluoro-N-methylbenzamide

HRID 624530
ノート
印刷プレビュー

反応式

HRID 624530 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.Cl[C:44]1[N:53]=[CH:52][C:51]2[C:46](=[CH:47][C:48]([Cl:54])=[CH:49][CH:50]=2)[N:45]=1.C(=O)([O-])[O-].[K+].[K+]>C(O)CCC.O>[Cl:54][C:48]1[CH:47]=[C:46]2[C:51]([CH:52]=[N:53][C:44]([N:22]3[CH2:23][CH:24]([C:26]4[C:27]([C:32]5[CH:41]=[CH:40][C:35]([C:36]([NH:38][CH3:39])=[O:37])=[C:34]([F:42])[CH:33]=5)=[N:28][CH:29]=[CH:30][N:31]=4)[CH2:25]3)=[N:45]2)=[CH:50][CH:49]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 11430Potassium CarbonateHCID 124139292,7-DichloroquinazolineHCID 867054064-(3-(Azetidin-3-YL)pyrazin-2-YL)-2-fluoro-N-methylbenzamide tris(2,2,2-trifluoroacetate)

生成物 1

HCID 727148524-(3-(1-(7-Chloroquinazolin-2-YL)azetidin-3-YL)pyrazin-2-YL)-2-fluoro-N-methylbenzamide収率 92.3%

試薬・触媒・溶媒 2

HCID 263
1-Butanol
溶媒
HCID 962Water溶媒

反応条件

温度
110 °C

実験手順

4-(3-(Azetidin-3-yl)pyrazin-2-yl)-2-fluoro-N-methylbenzamide tris(2,2,2-trifluoroacetate) (0.150 g, 0.239 mmol), 2,7-dichloroquinazoline (0.062 g, 0.310 mmol), and potassium carbonate (0.165 g, 1.19 mmol, Aldrich) were mixed in butan-1-ol (2 mL) in a sealed tube. The reaction mixture was stirred at 110° C. for 18 h. The reaction mixture was cooled to room temperature, diluted with water, and extracted with EtOAc. The organic layer was separated, washed with saturated sodium chloride, dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting crude mixture was purified via silica gel flash column chromatography eluting with 50% to 100% EtOAc in hexanes to yield give 99 mg (92%) of a light yellow solid. 1H NMR (400 MHz, chloroFORM-d) δ ppm 3.09 (d, J=4.50 Hz, 3 H) 4.29-4.38 (m, 1 H) 4.46-4.58 (m, 4 H) 6.75-6.85 (br. m., 1 H) 7.18 (dd, J=8.61, 1.56 Hz, 1 H) 7.36 (d, J=12.32 Hz, 1 H) 7.40 (dd, J=8.12, 1.27 Hz, 1 H) 7.60 (d, J=8.41 Hz, 1 H) 7.63 (br. s., 1 H) 8.27 (t, J=8.02 Hz, 1 H) 8.57 (d, J=2.15 Hz, 1 H) 8.65 (d, J=2.15 Hz, 1 H) 8.97 (s, 1 H). m/z=449 (M+1).

後処理

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionextracted with EtOAc
  3. customThe organic layer was separated
  4. washwashed with saturated sodium chloride
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe resulting crude mixture was purified via silica gel flash column chromatography
  9. washeluting with 50% to 100% EtOAc in hexanes
  10. customto yield

出典と根拠

ORDレコード
ord-246e60ab0f7d421695077e09d1843c49
出典データセット
uspto-grants-2016_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09303028B2

反応ノート

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