Cesium carbonate → tert-butyl 5-(3-((tert-butoxycarbonyl)amino)-2-chloro-5-cyanophenyl)octahydro-1H-pyrrolo[3,2-c]pyridine-1-carboxylate

HRID 921810Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 921810
Br[C:2]1[C:3]([Cl:18])=[C:4]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH:5]=[C:6]([C:8]#[N:9])[CH:7]=1.[N:19]1([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH:27]2[CH:22]([CH2:23][NH:24][CH2:25][CH2:26]2)[CH2:21][CH2:20]1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=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]>[C:13]([O:12][C:11]([NH:10][C:4]1[C:3]([Cl:18])=[C:2]([N:24]2[CH2:25][CH2:26][CH:27]3[N:19]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:20][CH2:21][CH:22]3[CH2:23]2)[CH:7]=[C:6]([C:8]#[N:9])[CH:5]=1)=[O:17])([CH3:16])([CH3:15])[CH3:14]

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 49761056(3aR,7aS)-rel-tert-Butyl octahydro-1H-pyrrolo[3,2-c]pyridine-1-carboxylateHCID 86708481Tert-butyl (3-bromo-2-chloro-5-cyanophenyl)carbamate

Produkt 1

HCID 89923255tert-butyl 5-(3-((tert-butoxycarbonyl)amino)-2-chloro-5-cyanophenyl)octahydro-1H-pyrrolo[3,2-c]pyridine-1-carboxylateAusbeute 56,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

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

Reaktionsbedingungen

Temperatur
105 °C

Versuchsvorschrift

A mixture of tert-butyl (3-bromo-2-chloro-5-cyanophenyl)carbamate (440 mg, 1.326 mmol), tert-butyl octahydro-1H-pyrrolo[3,2-c]pyridine-1-carboxylate (300 mg, 1.326 mmol), Pd2dba3 (121 mg, 0.133 mmol), BINAP (248 mg, 0.398 mmol), and cesium carbonate (1296 mg, 3.98 mmol) in Dioxane (12 mL) was evacuated and back filled with nitrogen 3× and heated at 105° C. overnight. The reaction mixture was filtered through a plug of celite and the filtrate was concentrated. The crude product was purified by flash chromatography on silica gel using an automated ISCO system (80 g column, eluting with 5-35% ethyl acetate/hexanes), tert-butyl 5-(3-((tert-butoxycarbonyl)amino)-2-chloro-5-cyanophenyl)octahydro-1H-pyrrolo[3,2-c]pyridine-1-carboxylate (358 mg) was obtained as a foaming solid.

Aufarbeitung

  1. customwas evacuated
  2. additionback filled with nitrogen 3×
  3. filtrationThe reaction mixture was filtered through a plug of celite
  4. concentrationthe filtrate was concentrated
  5. customThe crude product was purified by flash chromatography on silica gel using
  6. washan automated ISCO system (80 g column, eluting with 5-35% ethyl acetate/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-827a6eded83a41359efbbd9ed9305cb2
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09273057B2

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