1,1'-Carbonyldiimidazole → HCID 118317160, Verbindung

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Reaktionsgleichung

[C:1]([NH:4][CH2:5][C:6]1[CH:7]=[C:8]([N:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]2)[CH:9]=[CH:10][C:11]=1[NH2:12])(=[O:3])C.NC1C=CC(N2CCN(C(OC(C)(C)C)=O)CC2)=CC=1CN.C1N=CN(C(N2C=NC=C2)=O)C=1>C1COCC1>[O:3]=[C:1]1[NH:4][CH2:5][C:6]2[C:11](=[CH:10][CH:9]=[C:8]([N:13]3[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:23])[CH3:24])=[O:20])[CH2:15][CH2:14]3)[CH:7]=2)[NH:12]1

Komponenten

Reaktionsbedingungen

Temperatur: 80 °C

Versuchsvorschrift

Therefore an alternative approach was adopted in which benzaldehyde 11 was nitrated to the known benzaldehyde 12, which in turn was subjected to reductive amination by condensing it with ammonium hydroxide, using sodium borohydride as reducing agent to produce amine 13 in high yield. Acetylation amine 13 generated acetamide 14, which was reacted with tert-butyl piperazine-1-carboxylate under Buchwald-Hartwig conditions to afford intermediate 15 in good yield. Reduction of nitro group of 15 over Pd—C in a Parr apparatus produced intermediate 16 in 91% yield high yield. Exposure of intermediate 16 under basic conditions rendered the desired diamine 17 in good yield after column purifications. Reaction of 17 with CDI in THF, heating the mixture at 80° C. for 6 hours, gave access to the key intermediate 10 in an overall yield of 33% from 14. Exposure of intermediate 10 to trifluoroacetic acid in a mixture of methanol and dichloromethane finally furnished the desired key intermediate 18 (scheme 2).

Aufarbeitung

customin good yield after column purifications

Quellen und Nachweise

ORD-Eintrag: ord-1f18fe91a68a4dea8b22c44dfc4e1b98
Quelldatensatz: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US09199969B1

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