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 633985노트

반응식

HRID 633985 반응식
[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

참가 물질

8

반응물 5

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

생성물 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)acrylate수율 56%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 6228Dimethylformamide용매

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-a29d9d2055394102a7ce547cfa5cd8c1
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09321769B2

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