Phosphorus oxychloride → 5-(2-Chloroethyl)-1-(chloromethyl)-4-methylpyrimido[1,6-a]indole

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Reaction Steps

A mixture of 2-chloro-N-[(1,3,4,9-tetrahydro-1-methylpyrano[3,4-b]indol-1-yl)methyl]-acetamide (9.0 g, described in Example 8) and phosphorus oxychloride (200 ml) is refluxed for 60 minutes and evaporated slowly to dryness under reduced pressure (10 mm Hg, the final bath temperature 140° C.). The residue is dissolved in chloroform and the solution is washed quickly with ice-cold 5% solution of sodium hydroxide, dried over magnesium sulfate, filtered and evaporated. The residue is chromatographed through a column of silica gel (300 g) using chloroform. The eluates are evaporated and the residue is crystallized from ethyl acetate to obtain the title compound (5.5 g); mp 160°-161° C., nmr(CDCl3) δ2.53(s), 3.62(m), 4.94(s) and 7.10-8.20(m).

Provenance & Evidence