Abstract
The Michael addition-cyclodehydration of a 6-aminouracil and
alkynone proceeds to give 5-deazapterin derivatives with total control
of regiochemistry. This simple and facile cyclocondensation process
is catalyzed by zinc(II) bromide or ytterbium(III) trifluoromethanesulfonate
at 110 °C, providing the heteroannulated products in up
to 94% yield.
Key words
pyridopyrimidines - uracil derivatives - Bohlmann-Rahtz
heteroannulation - heterocycles - Lewis acids
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In a typical
experimental procedure, 4-(trimethylsilyl)but-3-yn-2-one 4a (0.34 g, 2.4 mmol) was added to a stirred solution
of 6-aminouracil 3a (0.31 g, 2.4 mmol)
and zinc(II) bromide (55 mg, 0.24 mmol) in DMSO (5 mL). The mixture was
stirred at 110 °C for 72 hours, allowed to cool and water (30
mL) was added. The precipitated solid was washed with water and
dried to give 6a (0.26 g, 60%)
as a pale yellow solid, mp >260 °C (decomp.) (Found:
C, 54.66; H, 4.27; N, 23.56. Calc. for C8 H7 N3 O2 :
C, 54.24; H, 3.98; N, 23.72%) (Found MH+ ,
178.0619. C8 H7 N3 O2 requires
178.0616); IR(nujol)/cm-1 :
3310, 3120, 1705, 1695; 1 H NMR (d
6
-DMSO,
400 MHz) δ(ppm) 11.41 (1 H, s, NH), 11.12 (1 H, s, NH),
7.96 (1 H, d, J = 7.9 Hz, 5-H),
6.92 (1 H, d, J = 7.9 Hz, 6-H),
2.33 (3 H, s, Me); 13 C NMR (d
6
-DMSO,
100 MHz)m/z (CI) 178 (MH+ , 24%).
