Propionitrile → (E)-tert-Butyl 3-(3-(2-(4-methylpiperazin-1-yl)ethyl)-2-oxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-6-yl)acrylate

HRID 83031ノート

反応式

HRID 83031 の反応式
[C:1]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])(=[O:4])[CH:2]=[CH2:3].[CH:10]([N:13]([CH:16]([CH3:18])C)[CH2:14][CH3:15])([CH3:12])C.[CH3:19]C1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.Br[C:42]1[CH:43]=[C:44]2[NH:50][C:49](=[O:51])[NH:48][C:45]2=[N:46][CH:47]=1.[C:52](#[N:55])CC>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:52][N:55]1[CH2:15][CH2:14][N:13]([CH2:10][CH2:12][N:50]2[CH2:19][C:44]3[CH:43]=[C:42](/[CH:3]=[CH:2]/[C:1]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4])[CH:47]=[N:46][C:45]=3[NH:48][C:49]2=[O:51])[CH2:16][CH2:18]1

参加物

8

反応物 5

HCID 7854PropionitrileHCID 15458tert-Butyl acrylateHCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 19244136-bromo-3H-imidazo[4,5-b]pyridin-2-ol

生成物 1

HCID 68338119(E)-tert-Butyl 3-(3-(2-(4-methylpiperazin-1-yl)ethyl)-2-oxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-6-yl)acrylate収率 56%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 6228Dimethylformamide溶媒

実験手順

tert-Butyl acrylate (2.74 mL, 18.6 mmol), diisopropylethylamine (1.6 mL, 9.8 mmol) and P(o-tolyl)3 (272 mg, 0.89 mmol) were successively added to a suspension of 6-bromo-1H-imidazo[4,5-b]pyridin-2(3H)-one (1.0 g, 4.67 mmol) in propionitrile (27 mL) and dimethylformamide (7 mL) at room temperature. The resulting mixture was purged with argon prior to the addition of palladium acetate (100 mg, 0.44 mmol). The mixture was then purged with argon a second time and refluxed overnight. The reaction mixture was filtered on Celite® and the filtrate was concentrated to dryness. The residue was partitioned between ethyl acetate (20 mL) and water (30 mL). The organic phase was washed with a saturated solution of sodium chloride (2×30 mL), dried over sodium sulfate, filtered and concentrated to dryness. The residue was triturated in diethyl ether to give the title product as a brown solid (667 mg, 56%).

後処理

  1. customThe resulting mixture was purged with argon
  2. customThe mixture was then purged with argon a second time
  3. temperaturerefluxed overnight
  4. filtrationThe reaction mixture was filtered on Celite®
  5. concentrationthe filtrate was concentrated to dryness
  6. customThe residue was partitioned between ethyl acetate (20 mL) and water (30 mL)
  7. washThe organic phase was washed with a saturated solution of sodium chloride (2×30 mL)
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated to dryness
  11. customThe residue was triturated in diethyl ether

出典と根拠

ORDレコード
ord-90639de35b084243b9cda134fefce179
出典データセット
uspto-grants-2014_09
特許番号
US08846711B2

反応ノート

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