1774
T. Nicola et al. / Tetrahedron 57 (2001) 1771±1777
157.4 (C±Ar), 154.3 (C-1), 137.1 (C±Ar), 121.1 (C±Ar),
120.5 (C±Ar), 89.7 (C-2), 73.1 (C-3), 70.3 (C-7), 52.5
(OCH3), 42.9 (C-8), 36.1 (C-6), 24.3 (CH3), 23.8 (C-5),
18.6 (C-4).
3.3. General procedure for the 7-oxo-2-octynoates 9
Typically, runs were performed with ca. 5 mmol of 8. The
stirred solution of oxalyl chloride (8 mmol) in 30 ml of
dichloromethane was treated at 2608C under nitrogen
with DMSO (17 mmol). After the end of the gas evolution
a solution of 8 (5.0 mmol) in 8 ml of dichloromethane was
added. The mixture was stirred for additional 45 min at
2608C and then treated with triethylamine (25 mmol).
The reaction mixture was warmed up to rt within 30 min,
treated with 40 ml of water and extracted with dichloro-
methane (3£100 ml). The combined organic phase was
washed with 40 ml of water, dried (MgSO4) and concen-
trated in vacuo. Puri®cation was accomplished by ¯ash
chromatography (SiO2, cyclohexane/ethyl acetate).
3.2.3. Methyl 7-hydroxy-8-quinolin-2-yloct-2-ynoate (8c).
72%, orange solid; mp 768C (diethyl ether/pentane). IR
(CCl4): 3395, 3055, 2950, 2240, 1720, 1600, 1505, 1435,
1255, 1080 cm21. 1H NMR (250 MHz): d8.16 (dd, J8.4,
2.2 Hz, 1H, Ar±H), 8.06 (dd, J8.5, 2.4 Hz, 1H, Ar±H),
7.84 (m, 1H, Ar±H), 7.74 (ddd, J8.5, 7.8, 1.4 Hz, 1H, Ar±
H), 7.56 (ddd, J8.1, 7.8, 2.4 Hz, 1H, Ar±H), 7.30 (m, 1H,
Ar±H), 6.0±5.5 (br, 1H, OH), 4.32±4.18 (m, 1H, 7-H), 3.76
(s, 3H, OCH3), 3.18±3.08 (m, 2H, 8-H), 2.46 (m, 2H, 4-H),
1.96±1.66 (m, 4H, 5-H, 6-H). 13C NMR (100 MHz):
d160.8 (C±Ar), 154.3 (C-1), 137.2 (C±Ar), 130.0
(C±Ar), 128.5 (C±Ar), 127.7 (C±Ar), 126.9 (C±Ar),
126.4 (C±Ar), 122.2 (C±Ar), 89.8 (C-2), 73.2 (C-3), 70.0
(C-7), 52.6 (OCH3), 43.7 (C-8), 36.1 (C-6), 23.9 (C-5), 18.7
(C-4). MS (Cl, isobutane): m/z (%)340 (7), 338 (7), 299
(20), 298 (100) [M111], 296 (3), 280 (4), 266 (5), 172 (6),
143 (23), 115 (3). HRMS (C18H19NO3): calcd 297.1365;
found 297.1358. C18H19N03 (297.4): calcd C 72.71, H
6.52, N 4.57; found C 72.74, H 6.44, N 4.71.
3.3.1. Methyl 7-oxo-8-pyridin-2-yloct-2-ynoate (9a). 77%
of a 7:1 mixture of 9a/90a (CDCl3/rt), orange oil. The analy-
tical data were obtained from the mixture of the tautomers.
IR (CCl4): 2950, 2240, 1720, 1645, 1595, 1470, 1435, 1250,
1
1075 cm21. H NMR (250 MHz) of 9a: d8.56 (m, 1H,
60-H), 7.67 (dt, J7.6, 1.8 Hz, 1H, 40-H), 7.21 (m, 2H,
30-H, 50-H), 3.93 (s, 2H, 8-H), 3.76 (s, 3H, OCH3), 2.70
(t, J7.0 Hz, 2H, 6-H), 2.37 (t, J7.0 Hz, 2H, 4-H), 1.85
1
(quin, J7.0 Hz, 2H, 5-H). H NMR (250 MHz) of 90a:
d8.20 (m, 1H, 60-H), 7.56 (dd, J7.6 Hz, J1.8 Hz, 1H,
40-H), 6.91 (m, 2H, 30-H, 50-H), 5.34 (s, 1H, 8-H), 3.76 (s,
3H, OCH3), 2.42 (t, J7.0 Hz, 2H, 6-H), 2.37 (t, J6.7 Hz,
2H, 4-H), 1.93 (m, 2H, 5-H). MS (70 eV, EI): m/z (%)245
(14) [M1], 244 (54), 217 (29), 214 (21), 189 (27), 186 (38),
148 (26), 93 (100), 92 (38). HRMS (C14H15NO3): calcd
245.1052; found 245.1052.
3.2.4. Methyl 7-hydroxy-8-isoquinolin-1-yloct-2-ynoate
(8d). 38%, yellow oil. IR (CCl4): 3420, 2950, 2240, 1720,
1565, 1435, 1255, 1080 cm21
.
1H NMR (250 MHz):
d8.38 (d, J5.8 Hz, 1H, Ar±H), 8.14 (m, J8.4 Hz, 1H,
Ar±H), 7.84 (dd, J7.6, 1.5 Hz, 1H, Ar±H), 7.71 (ddd,
J7.9, 6.7, 1.2 Hz, 1H, Ar±H), 7.71±7.54 (m, 3H, Ar±H),
7.62 (ddd, J8.2, 6.7, 1.5 Hz, 1H, Ar±H), 7.56 (d,
J5.8 Hz, 1H, Ar±H), 4.39±4.29 (m, 1H, 7-H), 3.76 (s,
3H, OCH3), 3.50 (dd, J16.5, 2.4 Hz, 1H, 8-H), 3.22 (dd,
J16.5, 9.8 Hz, 1H, 8-H), 2.49±2.43 (m, 2H, 4-H),
1.98±1.74 (m, 4H, 5-H, 6-H). 13C NMR (100 MHz):
d160.2 (C±Ar), 154.3 (C-1), 140.9 (C±Ar), 136.2
(C±Ar), 130.4 (C±Ar), 127.5 (C±Ar), 127.5 (C±Ar),
127.4 (C±Ar), 124.8 (C±Ar), 119.7 (C±Ar), 89.8(C-2),
73.2 (C-3), 69.2 (C-7), 52.6 (OCH3), 39.8 (C-8), 36.1
(C-6), 23.9 (C-5), 18.7 (C-4). MS (70 eV, El): m/z
(%)297 (4) [M1], 282 (8), 266 (20), 264 (17), 238 (10).
200 (13), 182 (13), 173 (11), 172 (70), 144 (52), 143 (100),
130 (20), 128 (13), 116 (15), 115 (45). HRMS (C18H19NO3):
calcd 297.1365; found 297.1361.
3.3.2. Methyl 7-oxo-8-(6-methylpyridin-2-yl)oct-2-yno-
ate (9b). 65% of a 4:1 mixture of 9b/90b (CDCl3/rt); yellow
oil. The analytical data were obtained from the mixture of
the tautomers. IR (CCl4): 2950, 2240, 1720, 1650, 1595,
1565, 1455, 1435, 1255, 1155, 1075 cm21 1H NMR
.
(250 MHz) of the 9b: d7.45 (t, J7.6 Hz, 1H, 40-H),
6.72 (m, 2H, 30-H, 50-H), 3.89 (s, 2H, 8-H), 3.75 (s, 3H,
OCH3), 2.69 (t, J7.0 Hz, 2H, 6-H), 2.44 (s, 3H, CH3),
2.47±2.34 (m, 2H, 4-H), 1.94 (quin, J7.0 Hz, 2H, 5-H).
1H NMR (250 MHz) of 90b: d7.55 (t, J7.6 Hz, 1H,
40-H), 7.03 (m, 2H, 30-H, 50-H), 5.31 (s, 1H, 8-H), 3.76 (s,
3H, OCH3), 2.54 (s, 3H, CH3), 2.47±2.34 (m, 2H, 4-H, 6-H),
1.85 (quin, J7.0 Hz, 2H, 5-H). MS (70 eV, El): m/z
(%)259 (3) [M1], 258 (5), 228 (9), 203 (10), 200 (13),
162 (13), 111 (12), 108 (11), 107 (100), 106 (19), 69 (21, 65
(9), 55 (9). HRMS (C15H17NO3): calcd 259.1208; found
259.1210.
3.2.5. Methyl 7-hydroxy-8-(6,7-dimethoxy-3,4-dihydro-
isoquinolin-1-yl)oct-2-ynoate (8e). 41%, yellow oil. H
1
NMR (250 MHz): d6.93 (s, 1H, Ar±H), 6.69 (s, 1H,
Ar±H), 4,90 (br, OH), 4.20±4.07 (m, 1H, 7-H), 3.92 (s,
6H, Ar±OCH3), 3.76 (s, 3H, OCH3), 3.75±3.50 (m, 2H,
30-H). 2.81 (m, 1H, 8-H), 2.76±2.57 (m, 3 H. 8-H, 40-H),
2.44 (m, 2H, 4-H), 1.97±1.61 (m, 4H, 5-H, 6-H). 13C NMR
(100 MHz): d166.6 (C-10), 154.3 (C-1), 151.3 (C±Ar),
147.7 (C±Ar), 131.3 (C±Ar), 122.1 (C±Ar), 110.5
(C±Ar), 108.5 (C±Ar), 89.8 (C-2), 76.1 (C-3), 68.2 (C-7),
56.4/56.0 (Ar±OCH3), 52.5 (OCH3), 46.2 (C-30), 39.9
(C-8), 37.8 (C-6), 25.6 (C-40), 23.8 (C-5), 18.7 (C-4).
MS (70 eV, El): m/z (%)359 (17) [M1], 341 (35), 340
(29), 326 (19), 310 (20), 298 (25), 282 (100), 266 (19),
244 (43), 242 (35), 205 (80), 190 (40), 178 (41), 150
(15), 77 (13). HRMS (C20H25NO5): calcd 359.1733;
found 359.1733.
3.3.3. Methyl 7-oxo-8-quinolin-2-yloct-2-ynoate (9c).
48% as a 1:4 mixture of 9c/90c (CDCl3/rt), orange solid,
mp 478C (diethyl ether/pentane). The analytical data were
obtained from the mixture of the tautomers. IR (CCl4):
3055, 2950, 2235, 1720, 1635, 1550, 1435, 1415, 1330,
1255, 1135, 1085 cm21 1H NMR (250 MHz) of 9c:
.
d8.17 (dd, J8.4, 3.2 Hz, 1H, Ar±H), 8.05 (dd, 1H,
J8.5, 2.4 Hz, Ar±H), 7.82 (ddd, J8.3, 7.9 Hz,
J1.4 Hz, 1H, Ar±H), 7.76±7.66 (m, 1H, Ar±H), 7.47
(m, 1H, Ar±H), 7.33 (m, 1H, Ar±H), 4.15 (s, 2H, 8-H),
3.73 (s, 3H, OCH3), 3.70±3.40 (m, 2H, 8-H), 2.77 (t,
J7.0 Hz, 2H, 6-H), 2.36 (t, J7.0 Hz, 2H, 4-H), 1.87