N,N-Dimethyloxamic acid → N'-(2-(5-(4-Fluorobenzyl)-1,3-thiazol-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 80704

Reaktionsgleichung

Reaktionsgleichung von HRID 80704
[NH2:1][C:2]12[CH2:10][CH2:9][CH:6]([CH2:7][CH2:8]1)[CH2:5][N:4]1[C:11](=[O:36])[C:12]([O:28]CC3C=CC=CC=3)=[C:13]([C:15]3[S:16][C:17]([CH2:20][C:21]4[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=4)=[CH:18][N:19]=3)[N:14]=[C:3]21.[CH3:37][N:38]([CH3:44])[C:39](=[O:43])[C:40](O)=[O:41].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:23]=[CH:22][C:21]([CH2:20][C:17]2[S:16][C:15]([C:13]3[N:14]=[C:3]4[C:2]5([NH:1][C:40](=[O:41])[C:39]([N:38]([CH3:44])[CH3:37])=[O:43])[CH2:8][CH2:7][CH:6]([CH2:9][CH2:10]5)[CH2:5][N:4]4[C:11](=[O:36])[C:12]=3[OH:28])=[N:19][CH:18]=2)=[CH:26][CH:25]=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 6796026810-amino-3-(benzyloxy)-2-(5-(4-fluorobenzyl)-1,3-thiazol-2-yl)-7,8,9,10-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-4(6H)-one

Produkt 1

HCID 136159586N'-(2-(5-(4-Fluorobenzyl)-1,3-thiazol-2-yl)-3-hydroxy-4-oxo-6,7,8,9-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl)-N,N-dimethylethanediamideAusbeute 15,32 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a stirred solution of 10-amino-3-(benzyloxy)-2-(5-(4-fluorobenzyl)-1,3-thiazol-2-yl)-7,8,9,10-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-4(6H)-one, Example 5 (35 mg, 0.085 mmol) in DMF (2 mL) was added 2-(dimethylamino)-2-oxoacetic acid (19.87 mg, 0.170 mmol), N,N-diisoproplylethylamine (0.119 mL, 0.679 mmol), HATU (64.5 mg, 0.170 mmol) and DMAP (5.18 mg, 0.042 mmol) and the resulting mixture stirred at room temperature for 16 h. The mixture was purified by preparative HPLC to afford the title compound (7 mg, 0.013 mmol, 15.32% yield) as a light green solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.17 (1H, br. s.), 9.04 (1H, br. s.), 7.87 (1H, br. s.), 7.36 (2H, dd, J=8.16, 5.65 Hz), 7.19 (2H, t, J=8.78 Hz), 4.29 (2H, s), 4.06 (2H, d, J=3.51 Hz), 3.04 (3H, s), 2.87 (3H, s), 2.33-2.45 (3H, m), 2.03-2.14 (2H, m), 1.79-1.90 (2H, m), 1.60-1.71 (2H, m). LCMS (M+H)=512.01.

Aufarbeitung

  1. customThe mixture was purified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-fdb635e6cc3e4b64a429941514f9e560
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08846659B2

Verknüpfte Notizen

Wird geladen…