Synthesis of Pyrimidine-Annelated Heterocycles
637
after usual workup the residue was subjected to column chromatography (silica, ethyl acetate:
benzene 1:3). The product was recrystallised from ethanol.
6-Bromo-1,3-dimethylhexahydroindolo[3,2-d]pyrimidine-2,4-dione (6; C12H16BrN3O2;
mixture of diastereomers)
Yield: 90%; gummy mass; 1H NMR ꢀCDCl3; ꢀ; 300 MHz: 4.86 (m, 1H), 3.59 (s, 3H), 3.41 (s, 3H),
2.79±2.89 (m, 1H), 2.63±2.73 (m, 1H), 2.09±2.10 (m, 1H), 1.39±2.06 (m, 6H) ppm; IR (neat):
ꢁ 2940, 1700, 1650, 1440 cm 1; UV/Vis (EtOH): ꢂmaxꢀ" 218 (2215), 300 (1874) nm; MS:
m=z 315, 313 (M ).
9-Bromo-1,3-dimethylhexahydrobicyclo[3.3.1]indolo[3,2-d]pyrimidine-2,4-dione
(7; C12H16BrN3O2; mixture of diastereomers)
1
Yield: 85%; m.p.: 150ꢁC; H NMR ꢀCDCl3; ꢀ; 300 MHz: 4.71±4.75 (m, 2H), 3.38 (s, 3H), 3.36
(s, 3H), 3.28±3.32 (m, 1H), 2.06±2.15 (m, 3H), 1.68±1.83 (m, 1H), 1.55±1.67 (m, 2H), 1.21±1.32
(m, 1H) ppm; IR (KBr): ꢁ 2940, 1700, 1650, 1440 cm 1; UV/Vis (EtOH): ꢂmaxꢀ" 218 (2235),
300 (1954) nm; MS: m=z 315, 313 ꢀM .
Attempted dehydrogenation of 6 and 7
Compound 6 (0.314 g, 1 mmol) was re¯uxed with 0.1 g 10% Pd/C in 2 cm3 diphenyl ether for 30 min.
It was then subjected to column chromatography over silica. Diphenyl ether was eluted with petrol
ether, and 8 was obtained when the column was eluted with ethyl acetate: benzene 1:9. The product
was recrystallized from EtOH. Similarly, 7 was re¯uxed with 10% Pd/C in diphenyl ether for 1 h.
However, only unchanged starting material was recovered in this case.
1,3-Dimethyl-indolo[3,2-d]pyrimidine-2,4-dione (8; C12H11N3O2)
1
Yield: 91%; m.p.: 225ꢁC; H NMR ꢀCDCl3; ꢀ; 300 MHz: 7.94±7.96 (m, 1H), 7.60±7.68 (m, 2H),
1
7.39±7.44 (m, 1H), 3.92 (s, 3H), 3.51 (s, 3H) ppm; IR (KBr): ꢁ 2940, 1700, 1640, 1440 cm
;
UV/Vis (EtOH): ꢂmaxꢀ" 220 (19007), 294 (12252) nm; MS: m=z 229 ꢀM :
Cyclization of 4 in concentrated sulfuric acid
Compound 4 (0.705, 3 mmol) was added to 4 cm3 of well-stirred concentrated sulfuric acid at 0±5ꢁC,
and stirring was continued for 2 h at this temperature. The reaction mixture was poured onto crushed
ice and extracted with 3 Â 20 cm3 CHCl3. The CHCl3 extract was washed with 2 Â 25 cm3 5%
NaHCO3 solution, 2 Â 25 cm3 H2O, and dried over Na2SO4. Removal of the solvent gave a crude
mass which was subjected to column chromatography over silica. 10 and 11 were obtained as white
solids using ethyl acetate:benzene 1:3 as the eluent.
1,3-Dimethylhexahydroindolo[3,2-d]pyrimidine-2,4-dione (10; C12H17N3O2;
mixture of diastereomers)
1
Yield: 28%; m.p.: 124ꢁC; H NMR ꢀCDCl3; ꢀ; 500 MHz: 4.57±4.56 (m, 1H), 3.41 (s, 3H), 3.38
(s, 3H), 2.98±3.00 (m, 1H), 2.35±2.38 (m, 1H), 1.55±2.05 (m, 6H), 1.24±1.32 (m, 2H) ppm; IR (KBr):
ꢁ 2940, 1700, 1650, 1440 cm 1; UV/Vis (EtOH): ꢂmaxꢀ" 217 (5617), 300 (5006) nm; MS:
m=z 235 ꢀM .