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tert-Butyl acrylate → (E)-3-[4-(3-Morpholin-4-yl-propyl)-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl]acrylic acid tert-butyl ester

HRID 1362089
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1362089
Br[C:2]1[CH:22]=[N:21][C:5]2[NH:6][C:7](=[O:20])[CH2:8][N:9]([CH2:11][CH2:12][CH2:13][N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[CH2:10][C:4]=2[CH:3]=1.[C:23]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])(=[O:26])[CH:24]=[CH2:25].C(N(C(C)C)C(C)C)C.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(#N)CC.CN(C=O)C.CCOCC.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:28]([O:27][C:23](=[O:26])/[CH:24]=[CH:25]/[C:2]1[CH:22]=[N:21][C:5]2[NH:6][C:7](=[O:20])[CH2:8][N:9]([CH2:11][CH2:12][CH2:13][N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[CH2:10][C:4]=2[CH:3]=1)([CH3:31])([CH3:30])[CH3:29]
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Komponenten

9

Edukt 4

HCID 15458tert-Butyl acrylateHCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 594569707-Bromo-4-(3-morpholin-4-yl-propyl)-1,3,4,5-tetrahydro-pyrido[2,3-e][1,4]diazepin-2-one

Produkt 1

HCID 59456935(E)-3-[4-(3-Morpholin-4-yl-propyl)-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl]acrylic acid tert-butyl ester
Ausbeute 55 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 167845palladium(II) acetateKatalysatorHCID 3283Diethyl EtherLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 7854PropionitrileLösungsmittel

Versuchsvorschrift

A suspension of 7-bromo-4-(3-morpholin-4-yl-propyl)-1,3,4,5-tetrahydro-pyrido[2,3-e][1,4]diazepin-2-one (5.70 g, 15.4 mmol) in propionitrile (120 mL) and DMF (30 mL) was de-oxygenated with Ar for 15 min. The mixture was treated with tert-butyl acrylate (9.0 mL, 61 mmol) and (i-Pr)2EtN (5.7 mL, 33 mmol) and was de-oxygenated with Ar for 10 min. Pd(OAc)2 (0.35 g, 1.6 mmol) and P(o-tol)3 (0.94 g, 3.1 mmol) were added simultaneously, and the mixture was de-oxygenated a third time for 5 min. The mixture was heated to reflux overnight, then allowed to cool. The mixture was diluted with Et2O (200 mL). The organic solution was filtered through Celite, washed with H2O (200 mL), dried over Na2SO4, filtered and then concentrated in vacuo. Purification by flash column chromatography (silica gel, CH2Cl2/MeOH, 97:3 to 96:4) gave the title compound (3.49 g, 55%) as a tan solid: MS (ESI) m/e 417 (M+H)+.

Aufarbeitung

  1. waitwas de-oxygenated with Ar for 10 min
  2. customfor 5 min
  3. temperatureThe mixture was heated
  4. temperatureto reflux overnight
  5. temperatureto cool
  6. filtrationThe organic solution was filtered through Celite
  7. washwashed with H2O (200 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customPurification by flash column chromatography (silica gel, CH2Cl2/MeOH, 97:3 to 96:4)

Quellen und Nachweise

ORD-Eintrag
ord-cd01d18806ed4f2f9384f65e99f88456
Quelldatensatz
uspto-grants-2011_02
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US07879872B2

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