Sodium Carbonate → 5-[2-(2-Chloro-pyridin-4-yl)-quinazolin-4-yl]-(1S,4S)-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester

HRID 729532

Reaktionsgleichung

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]2[CH2:14][CH:9]1[CH2:10][N:11]2[C:15]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[N:18]=[C:17](Cl)[N:16]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.[Cl:48][C:49]1[CH:54]=[C:53](B2OC(C)(C)C(C)(C)O2)[CH:52]=[CH:51][N:50]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.C(Cl)Cl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][C@@H:12]2[CH2:14][C@H:9]1[CH2:10][N:11]2[C:15]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[N:18]=[C:17]([C:53]2[CH:52]=[CH:51][N:50]=[C:49]([Cl:48])[CH:54]=2)[N:16]=1)=[O:7])([CH3:3])([CH3:4])[CH3:2]

Komponenten

Reaktionsbedingungen

Temperatur: 80 °C

Versuchsvorschrift

A solution of 5-(2-chloro-quinazolin-4-yl)-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (0.145 g, 0.4 mmol) in DME (2 mL) under nitrogen were added palladium acetate (0.0045 g, 0.02 mmol), tri-o-tolylphosphine (0.015 g, 0.048 mmol), and 2-chloro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)pyridine (0.19 g, 0.8 mmol), followed by 2M Na2CO3 (0.6 mL, 1.2 mmol). The resulting mixture was heated at 80° C. for 20 h. The reaction was diluted with methylene chloride and washed with saturated sodium bicarbonate and brine and dried (MgSO4). Flash chromatography of the crude product mixture with 25:10:65, 35:10:55, and 50:10:40 EtOAc-CH2Cl2-Hexane gave the title compound. MS (ES+): 438.2 [M+H]+.

Aufarbeitung

washwashed with saturated sodium bicarbonate and brine
dry with materialdried (MgSO4)

Quellen und Nachweise

ORD-Eintrag: ord-bcdf025d864e487690ea336c7565ef18
Quelldatensatz: uspto-grants-2009_09
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US07582631B2

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