N,N-Dimethyloxamic acid → N'-(2-(5-(4-Fluorobenzyl)-1,3,4-oxadiazol-2-yl)-3-hydroxy-4-oxo-6,7,8,9-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl)-N,N-dimethylethanediamide

HRID 80705Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 80705
[NH2:1][C:2]12[CH2:10][CH2:9][CH:6]([CH2:7][CH2:8]1)[CH2:5][N:4]1[C:11](=[O:29])[C:12]([OH:28])=[C:13]([C:15]3[O:16][C:17]([CH2:20][C:21]4[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=4)=[N:18][N:19]=3)[N:14]=[C:3]21.[CH3:30][N:31]([CH3:37])[C:32](=[O:36])[C:33](O)=[O:34].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CN(C1C=CN=CC=1)C>[F:27][C:24]1[CH:25]=[CH:26][C:21]([CH2:20][C:17]2[O:16][C:15]([C:13]3[N:14]=[C:3]4[C:2]5([NH:1][C:33](=[O:34])[C:32]([N:31]([CH3:37])[CH3:30])=[O:36])[CH2:10][CH2:9][CH:6]([CH2:7][CH2:8]5)[CH2:5][N:4]4[C:11](=[O:29])[C:12]=3[OH:28])=[N:19][N:18]=2)=[CH:22][CH:23]=1

Komponenten

6

Edukt 3

HCID 2760995N,N-Dimethyloxamic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 13641318610-Amino-2-(5-(4-fluorobenzyl)-1,3,4-oxadiazol-2-yl)-3-hydroxy-7,8,9,10-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-4(6H)-one

Produkt 1

HCID 136159587N'-(2-(5-(4-Fluorobenzyl)-1,3,4-oxadiazol-2-yl)-3-hydroxy-4-oxo-6,7,8,9-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl)-N,N-dimethylethanediamideAusbeute 22,64 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of 10-amino-2-(5-(4-fluorobenzyl)-1,3,4-oxadiazol-2-yl)-3-hydroxy-7,8,9,10-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-4(6H)-one, Intermediate 12 (20 mg, 0.042 mmol) in DMF (1.5 mL) was added 2-(dimethylamino)-2-oxoacetic acid (9.79 mg, 0.084 mmol), N,N-dissopropylethylamine (0.044 mL, 0.251 mmol), HATU (31.8 mg, 0.084 mmol) and DMAP (5.11 mg, 0.042 mmol) and the resulting mixture stirred at room temp for 3 h and then purified by preparative HPLC to afford the title compound (5 mg, 9.47 μmol, 22.64% yield) as a purple solid. 1H NMR (500 MHz, CDCl3) δ ppm 11.10 (1H, br. s.), 9.60 (1H, s), 7.54 (2H, dd, J=8.39, 5.34 Hz), 7.10 (2H, t, J=8.55 Hz), 4.35 (2H, s), 4.24 (2H, br. s.), 3.44 (3H, s), 3.13 (3H, s), 2.99-3.08 (3H, m), 2.54 (1H, br. s.), 2.03-2.13 (2H, m), 1.85-1.94 (2H, m), 1.72-1.81 (2H, m). LCMS (M+H)+=497.18.

Aufarbeitung

  1. custompurified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-6d099d90bf1c4840bd053172178a7816
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08846659B2

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