Benzeneethanamine, alpha-methyl-, phosphate (1:1) → 6-(2-Fluoropyridin-3-yl)-2-methylpyrimidin-4-amine

HRID 1622017

反応式

HRID 1622017 の反応式
[NH2:1][C:2]1[CH:7]=[C:6](Cl)[N:5]=[C:4]([CH3:9])[N:3]=1.[F:10][C:11]1[C:16](B(O)O)=[CH:15][CH:14]=[CH:13][N:12]=1.CC(N)CC1C=CC=CC=1.OP(O)(O)=O.C([O-])(=O)C.[K+]>O.CCO>[F:10][C:11]1[C:16]([C:6]2[N:5]=[C:4]([CH3:9])[N:3]=[C:2]([NH2:1])[CH:7]=2)=[CH:15][CH:14]=[CH:13][N:12]=1

参加物

7

反応物 4

HCID 62885Benzeneethanamine, alpha-methyl-, phosphate (1:1)HCID 2867546-Chloro-2-methylpyrimidin-4-amineHCID 517044Potassium AcetateHCID 27832702-Fluoropyridine-3-boronic acid

生成物 1

HCID 665999906-(2-Fluoropyridin-3-yl)-2-methylpyrimidin-4-amine収率 84.4%

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 vials was added 4-Amino-6-chloro-2-methylpyrimidine (SynChem) (0.500 g, 3.48 mmol), 2-fluoro-3-pyridineboronic acid (Aldrich) (0.687 g, 4.88 mmol), Amphos (Aldrich) (0.123 g, 0.174 mmol), potassium acetate (Aldrich) (0.653 mL, 10.45 mmol), EtOH (12 mL), and water (1.2 mL). The vial was degassed by bubbling N2 for 5 min then sealed off and microwave heated at 100° C. for 20 min. The reaction mixture was partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc (2×10 mL). The combined organic layers were dried over MgSO4 and concentrated. The crude product was purified by column chromatography (80 g, 20% to 40% acetone in hexanes) to afford the desired product as a yellow solid (600 mg). MS (ESI pos. ion) m/z: 205.1. 1H NMR (300 MHz, CDCl3) δ ppm 2.59 (s, 3H) 4.96 (br. s., 2H) 6.89 (s, 1H) 7.34 (ddd, J=7.34, 4.93, 1.90 Hz, 1H) 8.27 (dd, J=3.00, 1.53 Hz, 1H) 8.66 (ddd, J=9.76, 7.64, 2.05 Hz, 1H).

後処理

  1. customThe vial was degassed
  2. customby bubbling N2 for 5 min
  3. customthen sealed off
  4. customThe reaction mixture was partitioned between EtOAc and water
  5. extractionThe aqueous layer was extracted with EtOAc (2×10 mL)
  6. dry with materialThe combined organic layers were dried over MgSO4
  7. concentrationconcentrated
  8. customThe crude product was purified by column chromatography (80 g, 20% to 40% acetone in hexanes)

出典と根拠

ORDレコード
ord-6514806d4af54291b8b02ecae42b4d5b
出典データセット
uspto-grants-2014_07
特許番号
US08772480B2

関連ノート

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