446
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 2, February, 2003
Gorunenko et al.
fraction with Rf 0.5 was collected and concentrated to obtain
compound 10 as colorless crystals in a yield of 112 mg (53%),
m.p. 238—240 °C (from MeCN). IR, ν/cm–1: 3300—3600 (NH);
1782, 1728, 1662 (C=O). 1H NMR (DMSOꢀd6), δ: 3.20 (s, 3 H,
N(8)Me); 3.51 (s, 3 H, N(6)Me); 7.41 (s, 1 H, H(4)); 13.2 (br.s,
disappeared after deuteration, 1 H, NH). Found (%): C, 46.32;
H, 3.59; N, 27.12. C8H8N4O3. Calculated (%): C, 46.15; H, 3.85;
N, 26.92.
6,8ꢀDimethylꢀ3ꢀ(trifluoromethylsulfonyl)pyrimiꢀ
do[4,5ꢀc]pyridazineꢀ5,7(6H,8H )ꢀdione (6). Trifluoromethaneꢀ
sulfonic anhydride (0.2 mL, 1.2 mmol) was added portionwise
to a solution of compound 10 (207 mg, 1 mmol) in pyridine
(3 mL) cooled to 0 °C. The reaction mixture was stirred at 0 °C
for 1 h and then at 20 °C for 48 h. Then the reaction mixture was
diluted with water (3 mL) and the precipitate that formed was
filtered off. Compound 6 was obtained as colorless crystals in a
yield of 210 mg (68%), m.p. 159—160 °C (from PriOH). IR,
ν/cm–1: 3106 (C—H arom.); 1772, 1720 (C=O). 1H NMR
(CDCl3), δ: 3.50 (s, 3 H, N(8)Me); 3.89 (s, 3 H, N(6)Me); 8.06
(s, 1 H, H(4)). Found (%): C, 32.00; H, 2.06; N, 16.34.
C9H7F3N4O5S. Calculated (%): C, 31.76; H, 2.05; F, 16.76;
N, 16.47; S, 9.41.
1,2ꢀDisubstituted 6,8ꢀdimethylpyrrolo[3´,2´:3,4]pyrimiꢀ
do[4,5ꢀc]pyridazineꢀ7,9(6H,8H )ꢀdiones (11a—h,j) (general
procedure). A solution of compound 8 (1 mmol) in amine
(30—40 mL) was stirred at 20 °C for 15 min (in the case of
EtNH2, at 0 °C) and then AgPy2MnO4 (1 mmol) was added.
The completion of the reaction was determined chromatographiꢀ
cally. The reaction mixture was concentrated to dryness and the
residue was extracted with CHCl3. The extract was concenꢀ
trated to ∼5 mL and chromatographed on a column with
Al2O3 using CHCl3 as the eluent. The first yellow fraction
was collected and concentrated. The residue was recrystalꢀ
lized from PriOH and compound 11 was obtained as yellow
crystals.
3ꢀBenzoylmethylꢀ6,8ꢀdimethylpyrimido[4,5ꢀc]pyridazineꢀ
5,7(6H,8H )ꢀdione (15). A solution of compound 8a (292 mg,
1 mmol) in piperidine (25 mL) was stirred at 20 °C for 15 min
and then AgPy2MnO4 (385 mg, 1 mmol) was added. The reacꢀ
tion mixture was kept at 20 °C for one week and concentrated to
dryness. The residue was extracted with CHCl3. The extract was
concentrated to ∼5 mL and chromatographed on a column with
Al2O3 using CHCl3 as the eluent. The yellow fraction was colꢀ
lected and concentrated to obtain compound 15 as darkꢀyellow
crystals in a yield of 62 mg (20%), m.p. 236—238 °C (from
PriOH). IR, ν/cm–1: 3062 (C—H arom.); 1718, 1692, 1678
(C=O). 1H NMR (DMSOꢀd6), δ: 3.36 (s, 3 H, N(8)Me); 3.73
(s, 3 H, N(6)Me); 4.89 (s, 2 H, CH2); 7.54—8.10 (m, 5 H, Ph);
8.16 (s, 1 H, H(4)). Found (%): C, 62.10; H, 4.36; N, 18.15.
This study was financially supported by the Russian
Foundation for Basic Research (Project No. 01ꢀ03ꢀ
32338).
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Received April 18, 2002;
C
16H14N4O3. Calculated (%): C, 61.93; H, 4.52; N, 18.06.
in revised form September 11, 2002