Proton sponge → HCID 54583743, Verbindung

1,8-Bis-(dimethylamino)naphthalene (80 mg, 0.37 mmol) was added to a solution of 7-benzyl-2-(3-chlorobenzyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine of Preparation 28, Step C, (135 mg, 0.37 mmol) in dichloromethane (5 ml). Then 1-chloroethyl chloroformate (80.9 μl, 0.74 mmol) was added and stirred at room temperature for 16 h. The reaction mixture was diluted with dichloromethane (10 ml) then washed with 5% aqueous citric acid (15 ml). The organic phase was dried over magnesium sulphate and concentrated in vacuo. The residue was dissolved in methanol (5 ml) then heated to reflux, under nitrogen, for 1.5 h. The reaction mixture was concentrated in vacuo then the residue was partitioned between dichloromethane (10 ml) and 1N NaOH (10 ml). The organic phase was dried over magnesium sulphate and concentrated in vacuo. The residue was purified by column chromatography on silica gel, eluting with DCM:MeOH:0.880NH3 (100:0:0 to 90:10:1), to afford the title compound as a yellow oil in 18% yield, 18 mg.

1. washthen washed with 5% aqueous citric acid (15 ml)
2. dry with materialThe organic phase was dried over magnesium sulphate
3. concentrationconcentrated in vacuo
4. dissolutionThe residue was dissolved in methanol (5 ml)
5. temperaturethen heated
6. temperatureto reflux, under nitrogen, for 1.5 h
7. concentrationThe reaction mixture was concentrated in vacuo
8. customthe residue was partitioned between dichloromethane (10 ml) and 1N NaOH (10 ml)
9. dry with materialThe organic phase was dried over magnesium sulphate
10. concentrationconcentrated in vacuo
11. customThe residue was purified by column chromatography on silica gel
12. washeluting with DCM

ORD-Eintrag

ord-0dd13a66c7f4464d8b7e6c414a627724

Quelldatensatz

uspto-grants-2011_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07928099B2