Phosphorus oxychloride → 1-Methyl-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine

The solid N-[2-(1H-pyrrol-1-yl)ethyl]acetamide (8 g, described in Example 1) is added cautiously in small portions into phosphorus oxychloride (45 ml) upon stirring. The mixture is refluxed for 60 min, and evaporated under reduced pressure (1 mm Hg). The residue is dissolved in 600 ml of methanol, filtered, and diluted with 60 ml of water. Sodium borohydride (8 g) is then added over 40 min at 25° C. The reaction mixture is stirred overnight, concentrated in vacuo, rendered basic with 10% ammonium hydroxide, and extracted with chloroform. The extracts are dried and evaporated to give a residue (5.79) of the title compound, nmr(CDCl3) δ 1.38(d), 1.90(s), 3.25(m), 3.80(d), 3.86(d), 4.05(q), 5.85(dd), 6.14(t) and 6.53(dd). A solution of the title compound in ethanol and a solution of an equimolar amount of maleic acid in ethanol are combined. The resulting solution is concentrated to obtain the maleate salt of the title compound: mp 137°-138° C., uv(MeOH) λmax 210 nm; ε=15000, and anal. calc'd. for C8H12N2.C4H4O4 : C, 57.13% H, 6.39% N, 11.11% and found: C, 57.16% H, 6.44% N, 10.86%.

1. temperatureThe mixture is refluxed for 60 min
2. customevaporated under reduced pressure (1 mm Hg)
3. dissolutionThe residue is dissolved in 600 ml of methanol
4. filtrationfiltered
5. additiondiluted with 60 ml of water
6. additionSodium borohydride (8 g) is then added over 40 min at 25° C
7. stirringThe reaction mixture is stirred overnight
8. concentrationconcentrated in vacuo
9. extractionextracted with chloroform
10. customThe extracts are dried
11. customevaporated

ORD record

ord-cdf1079d8d4940d9b2f6965dc6fb451a

Source dataset

uspto-grants-1980_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04188389