Phosphorus oxychloride → 5-(2-Chloroethyl)-1-(chloromethyl)-4-methylpyrimido[1,6-a]indole
Reaction equation
[Cl:1][CH2:2][C:3]([NH:5][CH2:6][C:7]1([CH3:20])[C:12]2[NH:13][C:14]3[C:19]([C:11]=2[CH2:10][CH2:9]O1)=[CH:18][CH:17]=[CH:16][CH:15]=3)=O.P(Cl)(Cl)([Cl:23])=O>>[Cl:23][CH2:9][CH2:10][C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[N:13]2[C:3]([CH2:2][Cl:1])=[N:5][CH:6]=[C:7]([CH3:20])[C:12]=12Participants
Procedure
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).
Workup
- temperatureis refluxed for 60 minutes
- customevaporated slowly to dryness under reduced pressure (10 mm Hg
- customtemperature 140° C.
- dissolutionThe residue is dissolved in chloroform
- washthe solution is washed quickly with ice-cold 5% solution of sodium hydroxide
- dry with materialdried over magnesium sulfate
- filtrationfiltered
- customevaporated
- customThe residue is chromatographed through a column of silica gel (300 g)
- customThe eluates are evaporated
- customthe residue is crystallized from ethyl acetate
Sources & evidence
- ORD record
- ord-91da242007414d8492bb4122ea2a5751
- Source dataset
- uspto-grants-1981_12
- Patent number
- US04307234
Reaction notes
Loading…