TABLE 3. Syn th esis of 2-Hyd r oxym eth ylqu in a zolon es
(d, J ) 6.2 Hz, 1H), 7.45 (d, J ) 9.0 Hz, 2H), 2.18 (s, 3H). Anal.
Calcd for C15H11N3O3: C, 64.05; H, 3.94; N, 14.94. Found: C,
64.00; H, 3.70; N, 14.99.
Gen er a l P r oced u r e for t h e Syn t h esis of 2-H yd r oxy-
m eth yl-4-qu in a zolon es. Meth od A: To a slurry of 2-acetoxy-
methyl-4-quinazolones (1 mmol) in MeOH (4 mL) at rt was added
K2CO3 (2.5 mmol). The mixture was stirred at rt for an
additional 20 min. Water (10 mL) was added slowly, and the
product precipitated. The slurry was filtered and dried under
vacuum.
Meth od B: To a slurry of 2-acetoxymethyl-4-quinazolones (1
mmol) in MeOH (4 mL) at rt was added K2CO3 (2.5 mmol). The
mixture was stirred at rt for an additional 20 min. Water (10
mL) was added, followed by TBME (10 mL). The organic layer
was separated, dried under MgSO4, filtered, and concentrated
under vacuum to give a foamy solid.
Meth od C: To a slurry of 2-acetoxymethyl-4-quinazolones (1
mmol) in MeOH (4 mL) at rt was added K2CO3 (2.5 mmol). The
mixture was stirred at rt for an additional 20 min. Water (10
mL) was added, followed by TBME (10 mL). The organic layer
was separated, dried under MgSO4, and filtered. Hydrochloric
acid (37%, 1 mmol) was added, and the resulting hydrochloride
salt precipitates were filtered and dried under vacuum.
2-Hydr oxym eth yl-5,7-dim eth yl-3-(2-ch lor oph en yl)-4-oxo-
3,4-d ih yd r oqu in a zolin e-6-ca r boxylic a cid eth yl ester (2):
Method B; 1H NMR (DMSO-d6, 300 MHz) δ 7.65-7.50 (m, 5 H),
5.37 (t, J ) 6.0 Hz, 1 H, OH), 4.39 (q, J ) 7.2 Hz, 2H), 4.00
(dqab, J ) 33.2, 15.1, 6.0 Hz, 2H), 2.64 (s, 3H), 2.38 (s, 3H), 1.33
(t, J ) 7.2 Hz, 3H). Anal. Calcd for C20H19N2O4Cl: C, 62.10; H,
4.95; N, 7.24; Cl, 9.16. Found: C, 62.11; H, 4.82; N, 7.09; Cl,
9.02.
2-Hyd r oxym eth yl-5,7-d im eth yl-3-(4-m eth oxyp h en yl)-4-
oxo-3,4-d ih yd r oqu in a zolin e-6-ca r boxylic a cid eth yl ester
h yd r och lor id e sa lt (17a ‚HCl): Method C; mp 118-121 °C; 1H
NMR (DMSO-d6, 300 MHz) δ 7.79 (s, 1H), 7.39 (d, J ) 9.0 Hz,
2H), 7.12 (d, J ) 9.0 Hz, 2H), 6.33 (b, 2H), 4.40 (q, J ) 7.1 Hz,
2H), 4.16 (s, 2H), 3.84 (s, 3H), 2.64 (s, 3H), 2.40 (s, 3H), 1.34 (t,
J ) 7.1 Hz, 3H). Anal. Calcd for C21H23N2O5Cl: C, 60.22; H,
5.53; N, 6.69. Found: C, 60.64; H, 5.71; N, 6.65.
2-Hyd r oxym eth yl-5,7-d im eth yl-3-(4-n itr op h en yl)-4-oxo-
3,4-d ih yd r oqu in a zolin e-6-ca r boxylic a cid eth yl ester (17b):
Method A; mp 215-217 °C; 1H NMR (DMSO-d6, 300 MHz) δ
8.23 (d, J ) 9.2 Hz, 2H), 7.36 (s, 1H), 7.26 (d, J ) 9.2 Hz, 2H),
5.15 (s, 2H), 4.37 (q, J ) 7.1 Hz, 2H), 2.69 (s, 3H), 2.31 (s, 3H),
1.32 (t, J ) 7.1 Hz, 3H). Anal. Calcd for C20H19N3O6: C, 60.45;
H, 4.82; N, 10.57. Found: C, 60.37; H, 4.93; N, 10.66.
2-Hyd r oxym eth yl-3-(2-ch lor op h en yl)-4-oxo-3,4-d ih yd r o-
qu in a zolin e (18a ): Method B; mp 75-77 °C; 1H NMR (DMSO-
d6, 300 MHz) δ 8.30-7.40 (m, 8H), 5.39 (t, J ) 6.2 Hz, 1H), 4.05
(dqab, J ) 30, 15, 6.2 Hz, 2H). Anal. Calcd for C15H11N2O2Cl: C,
62.84; H, 3.87; N, 9.77; Cl, 12.37. Found: C, 62.69; H, 3.76; N,
9.60; Cl, 12.59.
2-Hyd r oxym et h yl-3-(4-m et h oxyp h en yl)-4-oxo-3,4-d ih y-
d r oqu in a zolin e (18b): Method A; mp 163-166 °C; 1H NMR
(DMSO-d6, 300 MHz) δ 8.14 (dd, J ) 7.9, 1.1 Hz, 1H), 7.88 (td,
J ) 7.6, 1.5 Hz, 1H), 7.74 (d, J ) 7.7 Hz, 1H), 7.55 (td, J ) 7.5,
1.1 Hz, 1H), 7.35 (d, J ) 8.9 Hz, 2H), 7.08 (d, J ) 8.9 Hz, 2H),
5.16 (s, 1H), 4.07 (s, 2H), 3.83 (s, 3H). Anal. Calcd for
C16H14N2O3: C, 68.08; H, 5.00; N, 9.92. Found: C, 67.95; H, 4.97;
N, 9.89.
Anal. Calcd for C22H21N2O5Cl: C, 61.61; H, 4.94; N, 6.53; Cl,
8.27. Found: C, 61.56; H, 4.71; N, 6.45; Cl, 8.30.
2-Acetoxym eth yl-3-(2-ch lor op h en yl)-4-oxo-3,4-d ih yd r o-
1
qu in a zolin e (12a ): mp 83-86 °C; H NMR (CDCl3, 300 MHz)
δ 8.25 (d, J ) 6.2 Hz, 1H), 7.75 (m, 2H), 7.30-7.60 (m, 5H), 4.70
(qab, J ) 32.0, 15.2 Hz, 2H), 2.00 (s, 3H). Anal. Calcd for
C17H13N2O3Cl: C, 62.25; H, 4.00; N, 8.54; Cl, 10.81. Found: C,
61.99; H, 3.72; N, 8.48; Cl, 10.76.
2-Meth yl-5,7-d im eth yl-3-(4-m eth oxyp h en yl)-4-oxo-3,4-d i-
h yd r oqu in a zolin e-6-ca r boxylic a cid eth yl ester (14a ): mp
104-106 °C; 1H NMR (CDCl3, 300 MHz) δ 7.35 (s, 1H), 7.15 (d,
J ) 9.0 Hz, 2H), 7.05 (d, J ) 9.0 Hz, 2H), 4.43 (q, J ) 7.0 Hz,
2H), 3.85 (s, 3H), 2.75 (s, 3H), 2.42 (s, 3H), 2.23 (s, 3H), 1.40 (t,
J ) 7.0 Hz, 3H). Anal. Calcd for C21H22N2O4: C, 68.83; H, 6.05;
N, 7.65. Found: C, 68.52; H, 5.88; N, 7.50.
2-Meth yl-5,7-d im eth yl-3-(4-n itr op h en yl)-4-oxo-3,4-d ih y-
d r oqu in a zolin e-6-ca r boxylic a cid eth yl ester (14b): mp
1
2-H yd r oxym et h yl-3-p h en yl-4-oxo-3,4-d ih yd r oq u in a zo-
lin e (18d ): Method A; mp 155-157 °C; 1H NMR (DMSO-d6, 300
MHz) δ 8.14 (dd, J ) 7.9, 1.1 Hz, 1H), 7.89 (td, J ) 7.0, 1.5 Hz,
1H), 7.77 (d, J ) 7.5 Hz, 1H), 7.65-7.45 (m, 6H), 5.23 (s, 1H),
4.06 (s, 2H). Anal. Calcd for C15H12N2O2: C, 71.42; H, 4.79; N,
11.10. Found: C, 71.12; H, 5.00; N, 11.13.
177-178 °C; H NMR (CDCl3, 300 MHz) δ 8.35 (d, J ) 9.0 Hz,
2H), 7.42 (d, J ) 9.0 Hz, 2H), 7.32 (s, 1H), 4.35 (q, J ) 7.0 Hz,
2H), 2.65 (s, 3H), 2.35 (s, 3H), 2.15 (s, 3H), 1.35 (t, J ) 7.0 Hz,
3H). Anal. Calcd for C20H19N3O5: C, 62.98; H, 5.02; N, 11.02.
Found: C, 62.98; H, 4.77; N, 10.95.
2-Meth yl-3-(4-m eth oxyph en yl)-4-oxo-3,4-dih ydr oqu in azo-
1
lin e (16a ): mp 167-170 °C; H NMR (CDCl3, 300 MHz) δ 8.25
Ack n ow led gm en t. We thank Mauricio Loo and
Noela Reel for the generous offer of anthranilic acid.
(d, J ) 6.2 Hz, 1H), 7.75 (m, 2H), 7.48 (m, 1H), 7.20 (d, J ) 9.0
Hz, 2H), 7.05 (d, J ) 9.0 Hz, 2H), 3.85 (s, 3H), 2.35 (s, 3H). Anal.
Calcd for C16H14N2O2: C, 72.16; H, 5.30; N, 10.52. Found: C,
72.08; H, 5.08; N, 10.58.
Su p p or tin g In for m a tion Ava ila ble: Text giving analytical
and spectral data for compounds 10a , 10b, 10c, 12b, 12c, 12d ,
17c, and 18c. This material is available free of charge via the
Internet at http://pubs.acs.org.
2-Met h yl-3-(4-n it r op h en yl)-4-oxo-3,4-d ih yd r oq u in a zo-
1
lin e (16b): mp 190-193 °C; H NMR (CDCl3, 300 MHz) δ 8.35
(d, J ) 9.0 Hz, 2H), 8.18 (d, J ) 6.2 Hz, 1H), 7.75 (m, 2H), 7.62
J O049118E
J . Org. Chem, Vol. 69, No. 19, 2004 6477