4-Chloro-6-methyl-1,3,5-triazin-2-amine → 4-(2-Fluoro-5-(morpholinomethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine

HRID 1812356ノート

反応式

HRID 1812356 の反応式
[F:1][C:2]1[C:7](B(O)O)=[CH:6][C:5]([CH2:11][N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)=[CH:4][N:3]=1.Cl[C:19]1[N:24]=[C:23]([CH3:25])[N:22]=[C:21]([NH2:26])[N:20]=1.C([O-])(=O)C.[K+]>CCO.O>[F:1][C:2]1[C:7]([C:19]2[N:24]=[C:23]([CH3:25])[N:22]=[C:21]([NH2:26])[N:20]=2)=[CH:6][C:5]([CH2:11][N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)=[CH:4][N:3]=1

参加物

6

反応物 3

HCID 305914-Chloro-6-methyl-1,3,5-triazin-2-amineHCID 517044Potassium AcetateHCID 66600372HCID 66600372、化合物

生成物 1

HCID 666112724-(2-Fluoro-5-(morpholinomethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine収率 26%

試薬・触媒・溶媒 2

HCID 702Ethanol溶媒HCID 962Water溶媒

反応条件

温度
100 °C

実験手順

To a 20 mL microwave reaction tube was added 2-fluoro-5-(morpholinomethyl)pyridin-3-ylboronic acid (Example 129, Step 3) (2.00 g, 8.33 mmol), 4-chloro-6-methyl-1,3,5-triazin-2-amine (Example 9, 0.501 g, 3.47 mmol), Am-Phos (Aldrich, 0.124 g, 0.175 mmol) and potassium acetate (Aldrich, 1.14 g, 11.6 mmol) in EtOH (10 mL) and water (1 mL). The mixture was degassed by bubbling argon through for 10 min. The tube was heated in a microwave reactor (Biotage) at 100° C. for 20 min. After the reaction mixture was cooled to room temperature, insoluble material was removed via filtration. The filtrate was partitioned between saturated aqueous sodium chloride (60 mL) and 10% isopropanol in chloroform (60 mL). The aqueous phase was extracted with 10% isopropanol in chloroform (2×60 mL). The combined organic phases were dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by silica gel column chromatography (100 g, eluent: iPrOH in CHCl3 0% to 25%) to afford 4-(2-fluoro-5-(morpholinomethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (0.27 g, 26% yield) as a white foam. 1H NMR (400 MHz, CDCl3) δ ppm 8.46 (dd, J=9.00, 2.35 Hz, 1H) 8.27 (s, 1H) 5.83 (br. s., 2H) 3.70-3.75 (m, 4H) 3.56 (s, 2H) 2.54 (s, 3H) 2.44-2.50 (m, 4H). m/z (ESI, positive ion): 305.0 (M+H)+.

後処理

  1. customThe mixture was degassed
  2. customby bubbling argon through for 10 min
  3. temperatureAfter the reaction mixture was cooled to room temperature
  4. custominsoluble material was removed via filtration
  5. customThe filtrate was partitioned between saturated aqueous sodium chloride (60 mL) and 10% isopropanol in chloroform (60 mL)
  6. extractionThe aqueous phase was extracted with 10% isopropanol in chloroform (2×60 mL)
  7. dry with materialThe combined organic phases were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude product was purified by silica gel column chromatography (100 g, eluent: iPrOH in CHCl3 0% to 25%)

出典と根拠

ORDレコード
ord-9e2aeee63e664262ac5008df1a488b89
出典データセット
uspto-grants-2013_01
特許番号
US08362241B2

反応ノート

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