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 2172638ノート

反応式

HRID 2172638 の反応式
[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

参加物

6

反応物 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

生成物 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)-one収率 37.1%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
60 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-daf0779548d34156a3ca0d5685fe8cb0
出典データセット
uspto-grants-2015_06
特許番号
US09056110B2

反応ノート

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