Water → N'-(3-(Benzyloxy)-2-((3-(4-fluorophenyl)-2-oxopropyl)carbamoyl)-4-oxo-6,7,8,9-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl)-N,N-dimethylethanediamide

HRID 80699Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 80699
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9](=[O:37])[CH2:10][NH:11][C:12]([C:14]2[N:15]=[C:16]3[C:22]4([NH:25][C:26](=[O:32])[C:27]([N:29]([CH3:31])[CH3:30])=[O:28])[CH2:23][CH2:24][CH:19]([CH2:20][CH2:21]4)[CH2:18][N:17]3[C:33](=[O:36])[C:34]=2[OH:35])=[O:13])=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:45][C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1.O>CN(C=O)C>[CH2:45]([O:35][C:34]1[C:33](=[O:36])[N:17]2[CH2:18][CH:19]3[CH2:24][CH2:23][C:22]([NH:25][C:26](=[O:32])[C:27]([N:29]([CH3:31])[CH3:30])=[O:28])([C:16]2=[N:15][C:14]=1[C:12](=[O:13])[NH:11][CH2:10][C:9](=[O:37])[CH2:8][C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1)[CH2:21][CH2:20]3)[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1

Komponenten

6

Edukt 4

HCID 962WaterHCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 67960391N'-(2-((3-(4-Fluorophenyl)-2-oxopropyl)carbamoyl)-3-hydroxy-4-oxo-6,7,8,9-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl)-N,N-dimethylethanediamide

Produkt 1

HCID 67960337N'-(3-(Benzyloxy)-2-((3-(4-fluorophenyl)-2-oxopropyl)carbamoyl)-4-oxo-6,7,8,9-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl)-N,N-dimethylethanediamideAusbeute 59,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a mixture of N′-(2-((3-(4-fluorophenyl)-2-oxopropyl)carbamoyl)-3-hydroxy-4-oxo-6,7,8,9-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl)-N,N-dimethylethanediamide, Intermediate 15 (140 mg, 0.273 mmol) in DMF (5 mL) was added K2CO3 (67.8 mg, 0.491 mmol) followed by (bromomethyl)benzene (0.049 mL, 0.409 mmol) and the resulting mixture stirred at room temp for 16 h. Water was then added and the mixture was extracted with ethyl acetate (2×50 mL), dried (Na2SO4), filtered and concentrated. The crude product was purified by silica gel chromatography to afford the title compound (140 mg, 0.162 mmol, 59.5% yield) as a yellow oil. 1H NMR (500 MHz, CDCl3) δ ppm 8.73 (1H, s), 8.31 (1H, s), 7.53-7.59 (2H, m), 7.31-7.38 (3H, m), 7.18-7.24 (2H, m), 7.02-7.07 (2H, m), 5.35 (2H, s), 4.73 (2H, s), 4.29 (2H, d, J=5.49 Hz), 4.16 (2H, d, J=3.66 Hz), 2.94 (3H, s), 2.91 (3H, s), 2.70-2.79 (2H, m), 2.53 (1H, br. s.), 1.98-2.12 (4H, m), 1.70-1.80 (2H, m). LCMS (M+H)=604.31.

Aufarbeitung

  1. extractionthe mixture was extracted with ethyl acetate (2×50 mL)
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product was purified by silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-caad076cfc2a42a486e36ec43c119bc7
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08846659B2

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