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

HRID 1362084Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1362084
Br[C:2]1[CH:23]=[N:22][C:5]2[NH:6][C:7](=[O:21])[CH2:8][N:9]([CH2:11][C:12]([N:14]3[CH2:19][CH2:18][N:17]([CH3:20])[CH2:16][CH2:15]3)=[O:13])[CH2:10][C:4]=2[CH:3]=1.[C:24]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])(=[O:27])[CH:25]=[CH2:26].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.C(Cl)Cl.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:29]([O:28][C:24](=[O:27])/[CH:25]=[CH:26]/[C:2]1[CH:23]=[N:22][C:5]2[NH:6][C:7](=[O:21])[CH2:8][N:9]([CH2:11][C:12]([N:14]3[CH2:19][CH2:18][N:17]([CH3:20])[CH2:16][CH2:15]3)=[O:13])[CH2:10][C:4]=2[CH:3]=1)([CH3:32])([CH3:31])[CH3:30]

Komponenten

9

Edukt 4

HCID 15458tert-Butyl acrylateHCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 594569067-Bromo-4-[2-(4-methyl-piperazin-1-yl)-2-oxo-ethyl]-1,3,4,5-tetrahydro-pyrido[2,3-e][1,4]diazepin-2-one

Produkt 1

HCID 59456905(E)-3-{4-[2-(4-Methyl-piperazin-1-yl)-2-oxo-ethyl]-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl}acrylic acid tert-butyl esterAusbeute 72,3 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 167845palladium(II) acetateKatalysatorHCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 7854PropionitrileLösungsmittel

Versuchsvorschrift

A suspension of 7-Bromo-4-[2-(4-methyl-piperazin-1-yl)-2-oxo-ethyl]-1,3,4,5-tetrahydro-pyrido[2,3-e][1,4]diazepin-2-one (1.39 g, 3.64 mmol) in propionitrile (32 mL) and DMF (8 mL) was de-oxygenated with Ar for 15 min. The mixture was treated with tert-butyl acrylate (2.1 mL, 14 mmol) and (i-Pr)2EtN (1.3 mL, 7.4 mmol) and then was de-oxygenated with Ar for 10 min. Pd(OAc)2 (83 mg, 0.37 mmol) and P(o-tol)3 (0.22 g, 0.73 mmol) were added simultaneously, and the mixture was de-oxygenated a third time for 10 min. The mixture was heated to reflux overnight, then allowed to cool. The resulting precipitate was isolated by filtration and dissolved in CH2Cl2. The solution was filtered through Celite and the solvent was removed in vacuo to give the title compound (1.13 g, 72%) as an off-white solid: MS (ESI) m/e 430 (M+H)+.

Aufarbeitung

  1. waitwas de-oxygenated with Ar for 10 min
  2. customfor 10 min
  3. temperatureThe mixture was heated
  4. temperatureto reflux overnight
  5. temperatureto cool
  6. customThe resulting precipitate was isolated by filtration
  7. filtrationThe solution was filtered through Celite
  8. customthe solvent was removed in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-c3260f92111c456db2e2af82a5703582
Quelldatensatz
uspto-grants-2011_02
Patentnummer
US07879872B2

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