Notes
J . Org. Chem., Vol. 65, No. 20, 2000 6779
(0.6832 g, 11.35 mmol) and 3,5-dimethylbenzaldehyde (1.12 mL,
8.33 mmol) stirred in dichloroethane (15 mL, anhydrous).
Oxalacetic acid (1.00 g, 7.57 mmol) was added to the reaction
mixture, and the reaction was heated to reflux for 12 h. The
reaction mixture was cooled to room temperature, and a white
precipitate formed upon cooling. The product was simply col-
lected by filtration to give a white powder 5 (1.3928 g, 75.1%
yield).
Eth yl 6-(3,5-Dim eth ylp h en yl)-2-oxo-1,2,3,6-tetr a h yd r o-
p yr im id in e-4-ca r boxyla te (11). To a solution of acid 5 (0.5217
g, 2.12 mmol) in dimethylformamide (DMF, 7 mL, anhydrous)
were added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hy-
drochloride (EDC, 0.4465 g, 2.33 mmol), 1-hydroxy-7-azabenzo-
triazole (HOAT, 0.3172 g, 2.33 mmol), and N-methylmorpholine
(NMM, 0.47 mL, 4.24 mmol). Ethanol (1 mL, absolute) was
added to the reaction, and the mixture was stirred overnight at
room temperature. The reaction mixture was diluted with water
(50 mL), extracted with ethyl acetate (2 × 50 mL), dried, filtered,
and concentrated. The residue was purified by MPLC eluting
with ethyl acetate and hexane (3:7, v/v). The product was isolated
6-P h en yl-2-oxo-1,2,3,6-tetr a h yd r op yr im id in e-4-ca r boxy-
1
lic Acid (6). H NMR (300 MHz, DMSO-d6) δ: 5.13-5.16 (m, 1
H), 5.77-5.79 (m, 1 H), 7.29-7.41 (m, 5 H), 7.79 (s, 1 H). 13C
NMR (75 MHz, DMSO-d6) δ: 163.30, 152.79, 144.11, 129.04,
128.06, 127.89, 126.45, 109.26, 55.08. Anal. Calcd for C11H10N2O3
× 0.1 mol H2O: C, 66.02%; H, 7.03%; N, 5.92%. Found: C,
66.11%; H, 7.47%; N, 6.26%.
1
as a colorless solid (0.5322 g, 91.0% yield). H NMR (300 MHz,
DMSO-d6) δ: 1.37 (t, J ) 2.79 Hz, 3 H), 2.37 (s, 6 H), 4.38 (q, J
) 7 Hz, 2 H), 7.23 (bs, 1 H), 7.68 (bd, J ) 7 Hz, 1 H), 7.69-7.73
(m, 3 H). Anal. Calcd for C26H31N2O3: C, 66.02%; H, 7.03%; N,
5.92%. Found: C, 66.11%; H, 7.47%; N, 6.26%.
6-(2,3-Dich lor op h en yl)-2-oxo-l1,2,3,6-tetr a h yd r op yr im i-
1
d in e-4-ca r boxylic Acid (7). H NMR (300 MHz, DMSO-d6) δ:
5.52-5.54 (m, 1 H), 5.78-5.79 (m, 1 H), 7.35-7:50 (m, 3 H), 7.62
(dd, J ) 7.89 and 1.44 Hz, 1 H). 13C NMR (75 MHz, DMSO-d6)
δ: 163.03, 152.81, 143.31, 132.49, 130.01, 129.37, 129.28,
128.622, 126.99, 105.57, 53.45. Anal. Calcd for C11H8Cl2N2O3:
C, 46.02%; H, 2.81%; N, 9.76%. Found: C, 45.89%; H, 2.60%; N,
9.64%.
6-(3,5-Dim eth ylp h en yl)-2-oxo-1,2,3,6-tetr a h yd r op yr im i-
d in -4-yl-(4-ch lor op h en yl)m eth a n on e (12). To solution of acid
5 (0.5217 g, 2.12 mmol) in DMF (7 mL, anhydrous) were added
EDC (0.4465 g, 2.33 mmol), NMM (0.47 mL, 4.24 mmol), HOAT
(0.3172 g, 2.33 mmol), and N,O-dimethylhydroxylamine hydro-
chloride (0.2275 g, 2.33 mmol). The reaction was stirred over-
night at room temperature. The reaction mixture was diluted
with water (50 mL), extracted with ethyl acetate (2 × 50 mL),
dried, filtered, and concentrated. The crude residue was solu-
bilized in THF (10 mL, anhydrous) and cooled to 0 °C with an
external ice-bath. 4-Chlorophenylmagnesium bromide was slowly
added, and the reaction was warmed to room temperature. After
stirring for 5 h, the reaction was quenched with brine (50 mL),
extracted with ethyl acetate (2 × 50 mL), dried, filtered, and
concentrated. The residue was purified by MPLC by eluting with
ethyl acetate and hexane (4:1, v/v). The ketone 12 was isolated
as a pale yellow solid (0.2713 g, 37% yield). 1H NMR (300 MHz,
CDCl3) δ: 2.41 (s, 6 H), 6.89-6.86 (m, 1 H), 7.26-7.40 (m, 1 H),
7.51 (d, J ) 8.54 Hz, 2 H), 7.56 (s, 1 H), 8.06 (d, J ) 8.52 Hz, 2
H). Anal. Calcd for C19H17N2O2: C, 66.96%; H, 5.03%; N, 8.22%.
Found: C, 66.83%; H, 5.34%; N, 8.12%.
6-(3-Nitr op h en yl)-2-oxo-1,2,3,6-tetr a h yd r op yr im id in e-4-
1
ca r boxylic Acid (8). H NMR (300 MHz, DMSO-d6) δ: 5.36-
5.38 (m, 1 H), 5.86-5.87 (m, 1 H), 7.50 (bs, 1 H), 7.70 (dd, J )
7.63 and 7.70 Hz, 1 H). 7.80 (d, J ) 7.70 Hz, 1 H), 8.01 (s, 1 H),
8.17-8.19 (m, 2 H). 13C NMR (DMSO-d6) δ: 163.11, 152.70,
148.33, 146.22, 133.27, 130.76, 128.81, 122.88, 121.05, 108.09,
54.32. Anal. Calcd for C11H9N3O5: C, 50.20%; H, 3.45%; N,
15.96%. Found: C, 49.89%; H, 3.27%; N, 15.73%.
6-Cycloh exyl-2-oxo-1,2,3,6-tetr a h yd r op yr im id in e-4-ea r -
1
boxylic Acid (9). H NMR (300 MHz, DMSO-d6) δ: 0.95-2.51
(m, 11 H), 3.87 (s, 1 H), 5.65-5.67 (m, 1 H), 6.81 (s, 1 H), 7.46
(s, 1 H). 13C NMR (75 MHz, DMSO-d6) δ: 163.15, 153.55, 129.55,
107.79, 56.37, 44.85, 27.68, 27.41, 26.03, 25.98. Anal. Calcd for
C
26H31N2O3 × 1.0 H2O: C, 66.02%; H, 7.03%; N, 5.92%. Found:
C, 66.1 1%; H, 7.47%; N, 6.26%.
6-(2-Th ien yl)-2-oxo-l,2,3,6-tetr a h yd r op yr im id in e-4-ca r -
boxylic Acid (10). 1H NMR (300 MHz, DMSO-d6) δ: 5.44-5.46
(m, 2 H), 5.80-5.82 (s, 1 H), 6.99 (d, J ) 3.09 Hz, 1 H), 7.46-
7:50 (m, 2 H), 7.94 (s, 1 H). 13C NMR (75 MHz, DMSO-d6) δ:
163.25, 160.03, 152.29, 148.37, 128.52, 127.34, 125.84, 124.38,
108.51, 50.50. Anal. Calcd for C9H8N2O3S: C, 48.21%; H, 3.60%;
N, 12.49%. Found: C, 48.01%; H, 3.68%; N, 12.41%.
Su p p or tin g In for m a tion Ava ila ble: Proton and/or car-
bon NMR spectra of all new compounds. This material is
J O005512A