1188
L. W. Deady and T.Rodemann
Vol. 38
This was reacted with ethyl acetoacetate, sodium ethoxide and
copper acetate by the method reported for the pyrido analogue [8]
to give 1c as a pink solid (69%), mp 120-122° (from acetonitrile);
H nmr (deuteriochloroform): δ 1.28 (t, 3H, J = 7.2 Hz,
roform (× 5). The combined organic extracts were dried over
magnesium sulfate and the solvent was removed at reduced pres-
sure. The residual solid was recrystallized from toluene to give
the product as a brown solid (0.09 g, 19 %), mp >230° (dec. after
1
1
CH CH ), 2.78 (s, 3H, C8-CH ), 4.21 (q, 2H, J = 7.1 Hz,
forming needles >200°). H nmr (deuteriochloroform): δ 3.70 (s,
2
3
3
CH CH ), 4.47 (s, 2H), 7.47 (t, 1H, J = 7.5 Hz), 7.65 (d, 1H, J =
3H, CH ), 7.57 (dd, 1H, J = 8.0, 4.6 Hz, H-7), 8.56 (s, 1H, H-3),
2
3
3
6.8 Hz), 7.74 (d, 1H, J = 8.1 Hz), 8.91 (s, 1H).
Anal. Calcd. for C NO : C, 65.92; H, 5.53; N, 5.13.
8.78-8.88 (m, 2H), 15.10 (s, 1H, COOH).
H
Anal. Calcd. for C H N O : C, 58.82; H, 3.95. Found: C,
15 15
4
10
8 2 3
Found: C, 65.48; H, 5.88; N, 5.55.
59.17; H, 3.88.
The water of the aqueous layer of the above workup was
removed at reduced pressure. Soxhlet extraction of the residue
with ethanol gave 11 (0.25 g, 74%) (for data see below).
4-(Dimethylaminomethylene)isochroman-1,3-dione [1] (2a).
Phosphoryl chloride (2 ml) was added, with stirring, to a solu-
tion of homophthalic acid (2.0 g) in dimethylformamide (10 ml)
at 0°. The mixture was stirred for a further 1 hour, then poured
onto ice/water and the precipitate was collected by filtration and
washed with water to give the product as a yellow solid (1.9 g,
86%), mp 142° (lit [1] 144-145°), sufficiently pure for further
2,6-Dimethyl-1-oxo-1,2-dihydrobenzo[b][1,6]naphthyridine-4-
carboxylic acid (3c).
Compound 2c (0.15 g) in phosphoryl chloride (50 ml) was
heated under reflux for 48 hours (dissolution occurred slowly
during the heating). The phosphoryl chloride was removed at
reduced pressure and water (30 ml) was added. The precipitate
that formed was collected by filtration and recrystallized from
dimethyl sulphoxide to give the product as a yellow solid (0.10 g,
1
reaction; H nmr (deuteriochloroform): δ 3.33 (s, 6H, CH ),
3
7.14-7.20 (m, 2H), 7.52 (t, 1H, J = 7.6 Hz), 7.87 (s, 1H), 8.12 (d,
1H, J = 8.5 Hz).
8-Dimethylaminomethylene-8H-pyrano[4,3-b]pyridine-5,7-
dione (2b).
1
70%), mp >300° (formed cubes >290°); H nmr (dimethyl sul-
foxide-d ): δ 2.75 (s, 3H, CH ), 3.67 (s, 3H, NCH ), 7.67 (t, 1H,
6
3
3
This was prepared from 1b [8], as for 2a. The yellow solid
which separated from the reaction mixture was collected by fil-
tration and washed with little cold dichloromethane to give the
J = 7.7 Hz, H-8), 7.95 (d, 1H, J = 6.6 Hz), 8.25 (d, 1H, J = 8.1
Hz), 8.83 (s, 1H), 9.52 (s, 1H), 16.03 (s, 1H, COOH).
Anal. Calcd. for C
H N O •0.2H O: C, 66.27; H, 4.60; N,
15 12 2 3 2
1
product (86%), mp >170° (dec.) [9]; H nmr (dimethyl sulfoxide-
10.30. Found: C, 66.59; H, 4.40; N, 10.36.
d ) [10]: δ 3.25 (s, 3H, CH ), 3.54 (s, 3H, CH ), 7.20 (dd, 1H, J =
6
3
3
Methyl 1-Oxo-1H-isochromene-4-carboxylate (4).
7.8, 5.0 Hz, H-3), 8.27 (dd, 1H, J = 7.8, 1.5 Hz, H-4), 8.66 (dd,
13
1H, J = 5.0, 1.5 Hz, H-2), 8.75 (s, 1H, =CHN); C nmr
Dry hydrogen chloride gas was passed through a stirring solu-
tion of 2a (0.5 g) in methanol (15 ml) at room temperature for 2
hours. The solution was heated under reflux for 2 hours and the
solvent was removed at reduced pressure. Water was added to the
residue and the mixture was extracted with chloroform (× 3). The
combined organic extracts were dried over magnesium sulfate
and the solvent was removed at reduced pressure to give the
product as a white solid (0.37 g, 79%), mp 96° (from
(dimethyl sulfoxide-d ): δ 44.8 (CH ), 48.5 (CH ), 85.7 (C-8),
6
3
3
113.2 (C-4a), 118.6 (C-3), 141.5 (C-4), 150.7 (C-2), 154.0
(C-8a), 156.9 (C-7), 161.3 (=CHN), 161.5 (C-5).
4-Dimethylaminomethylene-6-methyl-4H-pyrano[4,3-b]quino-
line-1,3-dione (2c).
This was prepared from 1c, as for 2a. The orange solid which
separated from the reaction mixture was collected by filtration
and washed with little cold dichloromethane to give the product
1
methanol/water) (lit [2] 97-98°); H nmr (deuteriochloroform): δ
3.83 (s, 3H, CH ), 7.47 (t, 1H, J = 7.3 Hz), 7.71 (t, 1H, J = 7.4
3
1
(87%), mp >295° (dec.- after forming needles >280°) [9]; H nmr
Hz), 8.08 (s, 1H, H-3), 8.19 (d, 1H, J = 7.6 Hz), 8.51 (d, 1H, J =
13
(dimethyl sulfoxide-d ): δ 2.69 (s, 3H, CH ), 3.30 (s, 3H, NCH ),
8.2 Hz); C nmr (deuteriochloroform): δ 51.9 (CH ), 109.6 (C),
6
3
3
3
3.59 (s, 3H, NCH ), 7.36 (t, 1H, J = 7.6 Hz, H-3), 7.68 (d, 1H,
120.1 (C), 125.1 (CH), 128.8 (CH), 129.6 (CH), 133.2 (C), 135.1
(CH), 152.4 (CH), 160.4 (C), 164.2 (C).
3
J = 7.0 Hz), 7.89 (d, 1H, J = 8.1 Hz), 8.81 (s, 1H), 8.93 (s, 1H).
2-Methyl-1-oxo-1,2-dihydroisoquinoline-4-carboxylic acid (3a).
7-Hydroxy-5-oxo-5H-pyrano[4,3-b]pyridine-8-carboxaldehyde
(5b).
Compound 2a (0.5 g) in phosphoryl chloride (10 ml) was heated
under reflux for 3 hours (dissolution occurred immediately on heat-
ing). The solution was poured onto crushed ice and the precipitate
was collected by filtration to give the product as a white solid (0.35
g, 81%), mp >240° (dec. with decarboxylation) (lit [1] 262-263°);
(a) A mixture of 2b (0.2 g) and acetic acid (50 ml) was heated
under reflux for 10 minutes. Solid was present throughout and,
after cooling, this was collected by filtration to give the yellow
1
product (0.15 g, 86%), mp >260° (dec.) (from methanol); H nmr
1
H nmr (dimethyl sulfoxide-d /deuteriochloroform): δ 3.57 (s, 3H,
(dimethyl sulfoxide-d ) [10]: δ 7.36 (t, 1H, J = 6.8 Hz, H-3),
6
6
CH ), 7.42 (t, 1H, J = 7.9 Hz), 7.62 (t, 1H, J = 8.7 Hz), 8.19 (s, 1H,
H-3), 8.29 (d, 1H, J = 7.9 Hz), 8.81 (d, 1H, J = 8.4 Hz).
8.56 (dd, 1H, J = 6.2, 1.4 Hz, H-2), 8.69 (dd, 1H, J = 8.0, 1.4 Hz,
3
13
H-4), 9.74 (s, 1H, CHO), 14.74 (broad s, 1H, OH);
C nmr
(dimethyl sulfoxide-d ): δ 90.3 (C-8), 115.2 (C-4a), 117.4 (C-3),
144.2 (C-2), 145.3 (C-4), 150.1 (C-8a), 160.2 (C-5), 161.8 (C-7),
186.9 (CHO). ESMS: m/z 190 (M-1).
6
6-Methyl-5-oxo-5,6-dihydro-[1,6]naphthyridine-8-carboxylic
Acid (3b).
Compound 2b (0.5 g) in phosphoryl chloride (50 ml) was
heated under reflux for 16 hours (dissolution occurred slowly
during the heating). The phosphoryl chloride was removed at
reduced pressure and water (30 ml) was added. The solution was
neutralized with 10% sodium hydroxide and extracted with chlo-
Anal. Calcd. for C H NO : C, 56.55; H, 2.64; N, 7.33. Found:
C, 56.59; H, 2.53; N, 7.38.
9
5
4
(b) Compound 2b in dimethyl sulfoxide-d in an nmr tube was
6
heated at 100° for 16 hours to give an nmr spectrum identical
with that above.