Water → tert-butyl 8-carbamoyl-6-chloro-7-(3-cyanophenyl)-3,4-dihydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylate

HRID 1630014

Reaktionsgleichung

Reaktionsgleichung von HRID 1630014
Br[C:2]1[C:3]([C:19](=[O:21])[NH2:20])=[C:4]2[CH2:9][N:8]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:7][CH2:6][N:5]2[C:17]=1[Cl:18].[C:22]([C:24]1[CH:25]=[C:26](B(O)O)[CH:27]=[CH:28][CH:29]=1)#[N:23].O.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].ClCCl>[C:19]([C:3]1[C:2]([C:28]2[CH:27]=[CH:26][CH:25]=[C:24]([C:22]#[N:23])[CH:29]=2)=[C:17]([Cl:18])[N:5]2[CH2:6][CH2:7][N:8]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:9][C:4]=12)(=[O:21])[NH2:20]

Komponenten

8

Edukt 4

HCID 962WaterHCID 10796Cesium carbonateHCID 27343253-Cyanophenylboronic acidHCID 66585083tert-butyl 7-bromo-8-carbamoyl-6-chloro-3,4-dihydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylate

Produkt 1

HCID 66584843tert-butyl 8-carbamoyl-6-chloro-7-(3-cyanophenyl)-3,4-dihydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylateAusbeute 53,5 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a solution under nitrogen of 6.50 g (17.2 mmol) of tert-butyl 7-bromo-8-carbamoyl-6-chloro-3,4-dihydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylate in 200 ml of tetrahydrofuran are added 2.52 g (17.2 mmol) of 3-cyanophenylboronic acid (CAS 150255-96-2), 10 ml of water, 16.8 g (52.4 mmol) of caesium carbonate and 1.68 g (2.06 mmol) of a complex of 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium (II) and dichloromethane (PdCl2(dppf).CH2Cl2—CAS 95464-05-4). The mixture is stirred for 6 hours at 100° C. and then for 15 hours at 80° C., then cooled to room temperature and filtered through Celite™. The Celite is rinsed with 200 ml of ethyl acetate and 30 ml of water are added to the combined filtrates. The organic phase is separated out by settling, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue obtained is chromatographed on a column of silica gel, eluting with a mixture of 2 to 50% ethyl acetate in dichloromethane, to give 3.69 g of tert-butyl 8-carbamoyl-6-chloro-7-(3-cyanophenyl)-3,4-dihydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylate in the form of a white solid after recrystallization from ethyl acetate and drying at 60° C. under reduced pressure.

Aufarbeitung

  1. waitfor 15 hours at 80° C.
  2. temperaturecooled to room temperature
  3. filtrationfiltered through Celite™
  4. washThe Celite is rinsed with 200 ml of ethyl acetate and 30 ml of water
  5. additionare added to the combined filtrates
  6. customThe organic phase is separated out
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue obtained
  11. customis chromatographed on a column of silica gel
  12. washeluting with a mixture of 2 to 50% ethyl acetate in dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-8822920961144761b42de7575688c324
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08791119B2

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