Molecules 2004, 9
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1.29-1.35 (m, 3H, CH2CH3), 3.81-3.87 (m, 2H, CH2keto), 4.25-4.31 (m, 2H, CH2CH3), 5.72 (s, CH enol),
7.21-7.41 (m, 5H, HAr), 12.00 (broad s, OH enol).
6-Hydroxy-4-(phenoxydifluoromethyl)-2-phenylpyrimidine (2). To a solution of benzamidine (0.12 g,
0.1 mmol) in 10 mL of dry acetonitrile was added 0.3 g (0.12 mmol) of 1. The mixture was stirred at
room temperature for 2 hr. The precipitate of 2 (0.06 g) was filtered off, washed with petroleum ether
and dried. The mother liquor was concentrated to 4 mL and kept at room temperature for 5 days. The
precipitate was filtered off, washed with petroleum ether several times and dried to obtain a total of
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0.29 g (93.5%) of 2 as colorless crystalline compound: Н-NMR (DMSO-d6) δ 6.77 (s, 1Н,
19
СНpyrimidine), 7.20-7.96 (m, 10Н, НAr), 11.13 (s, 1Н, exchangeable with D2O, ОН); F-NMR (DMSO-
d6) δ 9.63 (s, CF2ОAr); MS m/z 314, М+; Analysis: Calculated for C17H12F2N2O2: С 64.97; H 3.85; N
8.91. Found: С 64.81; H 3.97; N 8.94.
4-(Phenoxydifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one (3). To a solution of o-phenylene-
diamine (0.11 g, 0.1 mmol) in dry benzene (15 mL) was added 0.3 g (0.12 mmol) of 1. The mixture
was heated under reflux for 1.5 hr with a Dean-Stark device. The mixture was then cooled and kept at
5º for 0.5 hr. The precipitate was filtered off, washed with petroleum ether and dried to obtain 0.3 g
(66.2%) of 3 as white crystalline compound: 1Н-NMR (DMSO-d6) δ 3.43 (s, 2Н, СН2azepine), 7.22-7.50
(m, 9Н, НAr), 10.72 (s, 1Н, NH); 19F-NMR (DMSO-d6) δ 3.54 (s, CF2ОAr); МS m/z 302, М+;
Analysis: Calculated for C16H12F2N2O2: С 63.58; H 4.00; N 9.27. Found: С 63.58; H 4.05; N 9.31
2-(Phenoxydifluoromethyl)-6-methoxy-1H-quinoline-4-one (4). p-Anisidine (0.11 g, 0.14 mmol) was
suspended in polyphosphoric acid (15 mL). The suspension was heated to 60º and treated with 0.4 g
(0.16 mmol) of 1. The reaction mixture was then heated at 100º for 3 hr. After cooling the mixture was
treated with 200 mL of ice water. The solid formed was filtered off, washed several times with water
1
and a small amount of ether and dried to obtain 0.18 g (46%) of 4 as pale brown solid: Н-NMR
(DMSO-d6) δ 3.88 (s, 3Н, ОСН3), 6.98 (broad. s., 1Н, exchangeable with D2O, NH), 7.35-7.97 (m, 9Н,
НAr); 19F-NMR (DMSO-d6) δ 2.09 (s, CF2ОAr); МS m/z 317, М+; Analysis: Calculated for
C17H13F2NO2: С 67.77; H 4.35; N 4.65. Found: С 67.69; H 4.21; N 4.48.
1-(3-Chlorophenyl)-3-methyl-4-(phenoxydifluoromethyl)-6-hydroxypyrazolo[3,4-b]pyridine (5). To a
solution of 5-amino-1-(3-chlorophenyl)-3-methylpyrazole (0.2 g, 0.1 mmol) in glacial acetic acid (6
mL) was added 0.3 g (0.12 mmol) of 1. The mixture was heated under reflux for 6 hr. The solution was
then cooled to room temperature, poured into 20 mL of ice water and kept at 2º for 2 days. The
precipitate formed was filtered off, washed with petroleum ether and dried to obtain 0.36 g (90%) of 5
1
as white solid: Н-NMR (DMSO-d6) δ 2.61 (s, 3Н, СН3), 6.99 (s, 1Н, СН5), 7.30-7.40 (m, 4Н, НAr),
7.40-7.50 (m, 2H, HAr ), 7.56 (t, 1H, J = 8.5 Hz, H5’), 8.18 (broad d, 1H, J = 8.5Hz, H6’), 8.31 (broad
t, 1H, J = 2.0Hz, H2’), 12.23 (s, 1Н, ОН); 19F-NMR (DMSO-d6) δ 14.07 (s, CF2OPh). 13C-{1H}
NMR* (DMSO-d6) δ 15.3 (s, CH3), 104.6 (s, C5), 106.3 (s, C3a), 119.4 (s, C2’), 120.4 (s, C6’), 120.6
(t, J = 261.6 Hz, CF2), 121.9 (s, C3”, C5”), 125.9 (s, C4’), 126.9 (s, C4”), 130.5 (s, C2”, C6”), 131.2