Potassium Carbonate → 5-chloro-6-((3,5-difluoropyridin-2-yl)methoxy)-3-(5-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-2-methylphenyl)-2-methylpyrimidin-4(3H)-one

HRID 2172638노트

반응식

HRID 2172638 반응식
[Cl:1][C:2]1[C:3](=[O:27])[N:4]([C:10]2[CH:15]=[C:14]([C:16]3[CH:21]=[CH:20][N:19]=[C:18]([C:22]([OH:25])([CH3:24])[CH3:23])[N:17]=3)[CH:13]=[CH:12][C:11]=2[CH3:26])[C:5]([CH3:9])=[N:6][C:7]=1[OH:8].Cl[CH2:29][C:30]1[C:35]([F:36])=[CH:34][C:33]([F:37])=[CH:32][N:31]=1.C(=O)([O-])[O-].[K+].[K+].C1OCCOCCOCCOCCOCCOC1>CN(C)C=O>[Cl:1][C:2]1[C:3](=[O:27])[N:4]([C:10]2[CH:15]=[C:14]([C:16]3[CH:21]=[CH:20][N:19]=[C:18]([C:22]([OH:25])([CH3:23])[CH3:24])[N:17]=3)[CH:13]=[CH:12][C:11]=2[CH3:26])[C:5]([CH3:9])=[N:6][C:7]=1[O:8][CH2:29][C:30]1[C:35]([F:36])=[CH:34][C:33]([F:37])=[CH:32][N:31]=1

참가 물질

6

반응물 4

HCID 11430Potassium CarbonateHCID 2855718-Crown-6HCID 534037442-(Chloromethyl)-3,5-difluoropyridineHCID 1363878065-Chloro-6-hydroxy-3-{5-[2-(1-hydroxy-1-methyl-ethyl)-pyrimidin-4-yl]-2-methyl-phenyl}-2-methyl-3H-pyrimidin-4-one

생성물 1

HCID 715824105-chloro-6-((3,5-difluoropyridin-2-yl)methoxy)-3-(5-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-2-methylphenyl)-2-methylpyrimidin-4(3H)-one수율 37.1%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
60 °C

실험 절차

To a solution of Intermediate 1 (505 mg, 1.31 mmol) in N,N-dimethylformamide (3 mL) was added 2-chloromethyl-3,5-difluoro-pyridine from Step C (214 mg, 1.31 mmol), potassium carbonate (452 mg, 3.27 mmol) and 18-crown-6 (40 mg). The slurry was heated at 60° C. for eighteen hours. After cooling the reaction was partitioned between ethyl acetate and water. The organic layer was washed with water and brine and dried over magnesium sulfate. The slurry was filtered and concentrated in vacuo. The crude material was purified using normal phase chromatography (ethyl acetate/heptane) to provide the title compound as a colorless oil (250 mg, 37% yield). MS (M+H): 514; 1H NMR (400 MHz, chloroform-d) δ ppm, 1.64 (s, 6H), 2.16 (s, 3H), 2.21 (s, 3H), 5.62-5.72 (m, 2H), 7.28-7.30 (m, 1H), 7.54-7.58 (m, 2H), 7.92 (s, 1H), 8.14 (d, J=8.21 Hz, 1H), 8.40 (s, 1H), 8.78 (d, J=5.47, 1H).

후처리

  1. temperatureAfter cooling the reaction
  2. customwas partitioned between ethyl acetate and water
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationThe slurry was filtered
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified

출처 및 근거

ORD 기록
ord-daf0779548d34156a3ca0d5685fe8cb0
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09056110B2

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