N,N-Dimethylglycine → 6-((5-chloropyridin-3-yl)oxy)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

HRID 60426

反応式

HRID 60426 の反応式
[OH:1][C:2]1[CH:24]=[N:23][C:5]2[N:6]([CH3:22])[C:7](=[O:21])[N:8]([CH2:11][CH2:12][CH2:13][O:14][CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][O:16]3)[C:9](=[O:10])[C:4]=2[CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].CN(C)CC(O)=O.Br[C:39]1[CH:40]=[N:41][CH:42]=[C:43]([Cl:45])[CH:44]=1>O1CCOCC1.CC(=O)OCC.O.[Cu]I>[Cl:45][C:43]1[CH:44]=[C:39]([O:1][C:2]2[CH:24]=[N:23][C:5]3[N:6]([CH3:22])[C:7](=[O:21])[N:8]([CH2:11][CH2:12][CH2:13][O:14][CH:15]4[CH2:20][CH2:19][CH2:18][CH2:17][O:16]4)[C:9](=[O:10])[C:4]=3[CH:3]=2)[CH:40]=[N:41][CH:42]=1

参加物

9

反応物 4

HCID 673N,N-DimethylglycineHCID 10796Cesium carbonateHCID 6062563-Bromo-5-chloropyridineHCID 1188754886-hydroxy-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione2 回

生成物 1

HCID 1188754876-((5-chloropyridin-3-yl)oxy)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione収率 78.8%

試薬・触媒・溶媒 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
135 °C

実験手順

To a mixture of 6-hydroxy-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (See Compound 36, step 2, 500 mg, 1.49 mmol), CuI (85.2 mg, 0.45 mmol), Cs2CO3 (971.6 mg, 2.98 mmol) and 2-(dimethylamino)acetic acid (76.87 mg, 0.75 mmol) in dioxane (20 mL) was added 3-bromo-5-chloropyridine (717.3 mg, 3.73 mmol). The reaction was heated at 135° C. for 5 h followed by heating at 100° C. for 18 h, cooled to RT then diluted with EA (25 mL) and water (10 mL). The organic layer was washed with water (20 mL) and brine (20 mL), dried over Na2SO4 and concentrated to a residue which was purified by chromatography eluted with PE/EA (10:1 to 1:1) to give 6-((5-chloropyridin-3-yl)oxy)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (525 mg, 78.8% yield) as a yellow oil. LCMS [MH+-THP] 363 and TR=1.403 min.

後処理

  1. temperatureby heating at 100° C. for 18 h
  2. temperaturecooled to RT
  3. washThe organic layer was washed with water (20 mL) and brine (20 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated to a residue which
  6. customwas purified by chromatography
  7. washeluted with PE/EA (10:1 to 1:1)

出典と根拠

ORDレコード
ord-2944545b1f1949acb305312f1f68db17
出典データセット
uspto-grants-2016_09
特許番号
US09440972B2

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