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

HRID 1622017

반응식

HRID 1622017 반응식
[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

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 702Ethanol용매HCID 962Water용매

반응 조건

온도
100 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-6514806d4af54291b8b02ecae42b4d5b
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08772480B2

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