*
*
PMR spectrum (δ, ppm, J/Hz): 8a (CN): 2.36 [3H, s, C(3)
CH ], 2.39 + 2.61 (2H, m + m, AB-system, ArCH ),
3 2
pyraz
*
2.44 [3H, s, C(5)
CH ], 2.50 (3H, s, N
CH ), 2.66 + 2.88 (2H, m + m, AB-system, COCH CH), 2.70 + 3.05 (2H, m
pyraz
*
3
piperid 3 2
*
1
*
+ m, AB-system, NCH ), 3.71 (3H, s, N
CH ), 3.94 (2H, q, AB-system, J = 8.7, COCH CO), 3.99 (3H, s, OCH ), 4.22
2
pyraz
3
2
3
1
*
(1H, dd, J = 8.0, NCH), 5.84 (2H, s, OCH O), 6.24 (1H, s, CH
); 8b + 8c (EN): 2.36 [3H, s, C(3)
CH ], 2.39 + 2.62
CH ), 2.64 + 2.85 (2H, m + m, AB-system,
CH ), 3.99 (3H, s, OCH ), 4.24 (1H, dd,
3 3
2
arom
pyraz
3
*
*
(2H, m + m, AB-system, , ArCH ), 2.43 [3H, s, C(5)
CH ), 2.47 (3H, s, N
2
pyraz
*
3
piperid 3
*
*
COCH CH), 2.76 + 3.14 (2H, m + m, AB-system, NCH ), 3.72 (3H, s, N
2
2
pyraz
1
J = 8.1, NCH), 5.76 (1H, s, =CH), 5.83 (2H, s, OCH O), 6.26 (1H, s, CH
), 16.44 (1H, br.s, OH).
2
arom
Ethyl-4-(4-methoxy-6-methyl-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]isoquinolin-5-yl)-3-oxobutanoate (11a) was
prepared analogously to 8a from 1 and acetoacetic ester (10a) as light yellow-colored crystals, 66% yield, mp 61-62°C
(CHCl :CCl ).
3
4
PMR spectrum (δ, ppm, J/Hz): 11a (CN): 1.28 (3H, t, J = 7.2, CH CH ), 2.39 + 2.70 (2H, m + m, AB-system,
2
3
1
1
2
J = 13.3, ArCH ), 2.41 (3H, s, NCH ), 2.76 (2H, dd, AB-system, J = 6.4, J = 2.2, COCH CH), 2.82 + 3.02 (2H, m + m,
2
3
2
1
1
AB-system, J = 11.6, NCH ), 3.48 (2H, AB-q, J = 15.2, COCH CO), 3.97 (3H, s, OCH ), 4.04 (1H, dd, J = 8.0, NCH), 4.18
2
2
3
(2H, q, J = 7.2, OCH ), 5.83 (2H, s, OCH O), 6.24 (1H, s, CH
).
2
2
arom
4-(4-Methoxy-6-methyl-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]isoquinolin-5-yl)-pentan-2,4-dione (11b)wasprepared
analogouslyto 8a from 1 and actylacetone (10b) to give light cream-colored crystals, 76% yield, mp 111-112°C (CHCl :CCl ).
3
4
PMR spectrum (δ, ppm, J/Hz): 11b (EN): 2.03 (3H, s, COCH ), 2.35 (3H, s, NCH ), 2.38 + 3.06 (2H, m + m,
3
3
1
1
AB-system, J = 12.2, NCH ), 2.44 + 2.52 (2H, m + m, AB-system, J = 13.4, COCH C=), 2.66 + 2.80 (2H, m + m, AB-system,
J = 16.0, ArCH ), 3.99 (3H, s, OCH ), 4.09 (1H, dd, J = 9.5, J = 3.6, NCH), 5.51 (1H, s, HC=), 5.86 (2H, s, OCH O), 6.22
2
2
1
1
2
2
3
2
(1H, s, CH
), 15.55 (1H, br.s, OH); 11b (CN): 2.16 (3H, s, COCH ), 2.31 (3H, s, NCH ), 3.57 (2H, AB-q, J = 15.1,
3 3
arom
1
COCH CO), 4.03 (1H, dd, J = 8.6, NCH), remaining signals overlap those of the EN form.
2
Diethyl-2-(4-methoxy-6-methyl-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]isoquinolin-5-yl)malonate (12c). Asolution
of 1 (1.02 g, 4.0 mmol) in CHCl (8 mL) was added to a solution of diethylmalonate (10c, 0.70 g, 4.4 mmol) in CHCl (3 mL),
3
3
treated with ground anhydrous Na SO (1 g), stirred for 1 h at 20°C, and filtered through a paper filter. The desiccant was
2
4
washed with CHCl . The combined filtrate was evaporated in vacuo to a volume of 3 mL. The resulting solution was diluted
3
with hexane (15 mL) and cooled to -10°C. The resulting amorphous solid was separated, washed with a small amount of ether,
and recrystallized from hexane. Drying in a vacuum desiccator produced 12c (0.63 g, 40%) as colorless crystals, mp 72-73°C.
PMR spectrum (δ, ppm, J/Hz): 1.15 (3H, t, J = 6.7, CH ), 1.24 (3H, t, J = 6.7, CH ), 2.41 (3H, s, NCH ), 2.58 (2H,
3
3
3
1
m, ArCH ), 2.72 + 3.33 (2H, m + m, AB-system, J = 15.8, NCH ), 3.66 (1H, d, J = 7.3, OCCHCO), 3.93 (3H, s, OCH ), 4.48
2
2
3
(1H, d, J = 7.3, NCH), 4.17 (4H, m, J = 6.7, 2×COOCH ), 5.83 (2H, s, OCH O), 6.26 (1H, s, CH ).
arom
2
2
ACKNOWLEDGMENT
The work was supported by grant CRDF-008-XI.
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1.
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4.
5.
6.
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