Dimethylformamide → N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-6-cyanopyrrolo[1,2-a]pyrazine-3-carboxamide Tartrate

HRID 25165

Reaktionsgleichung

[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[C@@H:3]([NH:9][C:10]([C:12]1[N:13]=[CH:14][C:15]3[N:16]([C:18](Br)=[CH:19][CH:20]=3)[CH:17]=1)=[O:11])[CH2:2]2.[C:22]([OH:31])(=[O:30])[C@H:23]([C@@H:25]([C:27]([OH:29])=[O:28])[OH:26])[OH:24].[CH3:32][N:33](C=O)C>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:27]([CH:25]([CH:23]([C:22]([OH:31])=[O:30])[OH:24])[OH:26])([OH:29])=[O:28].[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[C@@H:3]([NH:9][C:10]([C:12]1[N:13]=[CH:14][C:15]3[N:16]([C:18]([C:32]#[N:33])=[CH:19][CH:20]=3)[CH:17]=1)=[O:11])[CH2:2]2

Komponenten

Reaktionsbedingungen

Temperatur: 95 °C

Versuchsvorschrift

To an argon sparged solution of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-6-bromopyrrolo[1,2-a]pyrazine-3-carboxamide (0.77 g, 2.14 mmol) in DMF (25 mL) is added zinc cyanide (0.26 g, 2.20 mmol), and tetrakis(triphenylphosphine)palladium (0) (0.25 g, 0.21 mmol). The resulting suspension is stirred at 95° C. for 48 h, then filtered through a pad of celite. The residue is purified using preparative chromatography (carried out on a Chiral OD column using a 40% IPA/heptanes each containing 0.1% diethylamine) to give a pale yellow oil that is salted with d-tartaric acid and crystallized from EtOH/Et2O to give a pale yellow solid. Yield 47%. HRMS (FAB) calcd for C16H17N5O+H 296.1511, found 296.1520.

Aufarbeitung

filtrationfiltered through a pad of celite
customThe residue is purified
customto give a pale yellow oil that
customcrystallized from EtOH/Et2O
customto give a pale yellow solid

Quellen und Nachweise

ORD-Eintrag: ord-35777fbdf51d4a96b2a0653b70a174ab
Quelldatensatz: uspto-grants-2005_02
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US06858613B2

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