Cesium carbonate → (3aR,6aR)-tert-butyl 1-(5-(3,5-difluorophenylcarbamoyl)pyridin-3-yl)hexahydropyrrolo[3,2-c]pyrrole-5(1H)-carboxylate

HRID 240526

Reaktionsgleichung

Reaktionsgleichung von HRID 240526
[NH:1]1[CH2:5][CH2:4][C@@H:3]2[CH2:6][N:7]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:8][C@H:2]12.Br[C:17]1[CH:18]=[N:19][CH:20]=[C:21]([CH:33]=1)[C:22]([NH:24][C:25]1[CH:30]=[C:29]([F:31])[CH:28]=[C:27]([F:32])[CH:26]=1)=[O:23].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:32][C:27]1[CH:26]=[C:25]([NH:24][C:22]([C:21]2[CH:33]=[C:17]([N:1]3[C@@H:2]4[C@@H:3]([CH2:6][N:7]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:8]4)[CH2:4][CH2:5]3)[CH:18]=[N:19][CH:20]=2)=[O:23])[CH:30]=[C:29]([F:31])[CH:28]=1

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 37818785tert-butyl (3aR,6aR)-2,3,3a,4,6,6a-hexahydro-1H-pyrrolo[2,3-c]pyrrole-5-carboxylateHCID 416011495-bromo-N-(3,5-difluorophenyl)nicotinamide

Produkt 1

HCID 67265787(3aR,6aR)-tert-butyl 1-(5-(3,5-difluorophenylcarbamoyl)pyridin-3-yl)hexahydropyrrolo[3,2-c]pyrrole-5(1H)-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

A suspension of (3aR,6aR)-tert-butyl hexahydropyrrolo[3,4-b]pyrrole-5(1H)-carboxylate (85 mg, 0.40 mmol, prepared as described in WO2001081347), the product from Example 53A (97 mg, 0.37 mmol), tris(dibenzylideneacetone)dipalladium(0) (13.4 mg, 0.015 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (25 mg, 0.044 mmol) and cesium carbonate (190 mg, 0.58 mmol) in anhydrous dioxane (4 mL) was heated at 90° C. for 18 hours. The reaction mixture was cooled and filtered through a glass frit. The filtrate was concentrated and the residue was purified by silica gel chromatography (EtOAc, Rf=0.4) to afford the title compound. MS (APCI) m/z=445 (M+H)+.

Aufarbeitung

  1. temperatureThe reaction mixture was cooled
  2. filtrationfiltered through a glass frit
  3. concentrationThe filtrate was concentrated
  4. customthe residue was purified by silica gel chromatography (EtOAc, Rf=0.4)

Quellen und Nachweise

ORD-Eintrag
ord-164d96d3bf3f4625ba5fcad317a66c98
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08648084B2

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