S.-W. Rhee et al.
to stand at RT (room temperature) for 3 days. The solid–gum
mixture was filtered, and the yellow solid–gum mixture was
dissolved in hot MeOH. The solution was chilled at ꢁ101C for 18 h.
The pale yellow solid was filtered to give 2.1g (43%) of TBZ (4a).
TLC: Rf = 0.62; silica gel; 4% MeOH/96% CH2Cl2.
MS: (DCl-NH3) m/z 318 (M1H).
3-(Dimethylaminomethyl)-5-methyl-5-hexen-2-one (8)
mixture of 5-methyl-5-hexen-2-one (7, 25 g, 0.22 mol),
A
diethylamine hydrochloride (18.3 g, 0.223 mol) and paraformal-
dehyde (10.3 g, 0.35 mol) in EtOH (300 mL) was refluxed for 18 h,
protected from moisture. The solution was evaporated to a
semisolid. Half the semisolid was dissolved in CH2Cl2 (100 mL)
and the solution was washed with saturated sodium bicarbo-
nate solution to neutralize the amine hydrochloride. The CH2Cl2
solution was dried (MgSO4), filtered, and evaporated to dryness.
The NMR showed a mixture of 3-(dimethylaminomethyl)-5-
methyl 5-hexen-2-one (8) and 1-(dimethylamino)-6-methyl-6-
hepten-3-one. The oil was chromatographed on a silica gel
column and eluted with CH2Cl2 to give 500 mg of oil (3%) of the
desired product (8).
UV: (EtOH) lmax 282.0 nm (e 4431).
1H NMR: (300 MHz, CDCl3) d 6.61 (s, 1H), 6.55 (s, 1H), 3.85
(s, 3H), 3.82 (s, 3H), 3.51 (br dd, 1H), 3.29 (dd, 1H), 3.13 (m, 2H),
2.90 (dd, 1H), 2.75 (m, 2H), 2.57 (m, 2H), 2.35 (t, 1H), 1.81 (ddd,
1H), 1.65 (m, 1H), 1.04 (ddd, 1H), 0.92 (d, 3H), 0.89 (d, 3H) ppm.
13C NMR: (75 MHz, CDCl3) d 210.00, 147.86, 147.54, 128.60,
126.11, 111.53, 107.94, 62.48, 61.52, 56.01, 55.92, 50.58, 47.62,
47.57, 36.09, 29.38, 25.44, 23.21, 22.11 ppm.
EA: Anal. Calc for C19H17NO3: C, 71.89; H, 8.57; N, 4.41. Found C,
72.15; H, 8.69; N, 4.47.
HPLC: Brownlee 25 cm ꢀ 4.6 mm silica gel column; 30%
isopropanol/70% hexane; 1 mL/min; ret. time 5.94 min; purity
499.5%.
1H NMR: (300 MHz, CDCl3) d 4.75 (d, 2H), 3.10 (m, 1H), 2.88
(dd, 1H), 2.35 (m, 2H), 2.35 (s, 6H), 2.20 (s, 3H), 2.07 (dd, 1H), 1.74
(s, 3H) ppm.
1,3,4,6,7,11b-Hexahydro-3-(2-methylprop-2-enyl)-9,10-di-
methoxy-2-oxo-2H-benzo[a]quinolizine (9)
1,3,4,6,7,11b-Hexahydro-3-isobutyl-9,10-dimethoxy-2-oxo-
2H-benzo[a]quinolizine (5)
To a solution of 3,4 dihydro-6,7-dimethoxyisoquinoline hydro-
chloride (3, 0.540 g, 15.4 mmol) in cold H2O (20 mL) on an ice
water bath was added 3-(dimethylaminomethyl)-5-methyl
5-hexan-2-one (8, 3.15 g, 18.3 mmol) as the free base with
stirring. Precipitate formed within 3 h, and stirring was
continued for 5 days. The yellow solid was filtered and then
dissolved in hot MeOH. The solution was chilled at ꢁ101C for
18 h, resulting in a pale yellow solid, which was filtered to give
140 mg (29%) of 1,3,4,6,7,11b-hexahydro-3-(2-methyl-2-prope-
nyl)-9,10-dimethoxy-2-oxo-2H-benzo[a]quinolizine (9).
TLC: Rf = 0.62; silica gel; 4% MeOH/96% CH2Cl2.
To TBZ (4, 317 mg, 1.00 mmol) and chloranil (260 mg, 1.05 mmol)
was added benzene (30 mL), and mixture was refluxed for 2.5 h.
To the dark solution plus insoluble precipitate was added
benzene (50 mL) and the mixture was washed with 30 mL of 2 N
sodium hydroxide and H2O. The benzene solution was dried
(MgSO4), filtered, and evaporated to dryness. The residue was
crystallized from ethyl acetate (EtOAc)/hexane to give 120 mg
(38%) of a gray solid (5).
TLC: Rf = 0.25; silica gel; 4% MeOH/96% CH2Cl2.
MS: (DCl-NH3) m/z 316 (M1H).
UV: (EtOH) lmax 284.4 nm (e 38,900).
UV: (EtOH) lmax 361.2nm (e 17,900), 284.4 (9,932), 238.0 (21,300).
1H NMR: (300 MHz, CDCl3) d 7.14 (s, 1H), 6.65 (s, 1H), 5.61
(s, 1H), 3.89 (s, 3H), 3.85 (s, 3H), 3.64 (dd, 1H), 3.37 (ddd, 2H), 3.29
(dd, 1H), 2.93 (m, 1H), 2.43 (ddd, 1H), 1.70 (m, 2H), 1.26 (m, 1H),
0.96 (d, 3H); 0.90 (d, 3H) ppm.
13C NMR: (75 MHz, CDCl3) d 195.43, 156.48, 151.51, 148.11,
128.91, 120.89, 110.44, 108.38, 94.32, 56.06, 55.86, 49.08, 42.10,
37.52, 28.50, 25.57, 23.50, 21.88 ppm.
1H NMR: (300 MHz, CDCl3) d 6.62 (s, 1H), 6.56 (s, 1H), 4.77
(d, 2H), 3.86 (s, 3H), 3.84 (s, 3H), 3.51 (br dd, 1H), 3.29 (dd, 1H),
3.13 (m, 2H), 2.95 (dd, 1H), 2.88 (m, 1H), 2.60 (m, 2H), 2.32 (t, 1H),
1.95 (dd, 1H), 1.74 (t, 3H) ppm.
13C NMR: (75 MHz, CDCl3) d 209.3, 147.9, 147.57, 142.75,
128.49, 126.14, 112.21, 111.55, 107.94, 62.47, 60.70, 56.03, 55.94,
50.62, 47.55, 47.09, 34.47, 29.36, 22.26 ppm.
EA: Anal. Calc for C19H17NO3 ꢂ 0.5 H2O: C, 71.33; H, 8.03; N, 4.38.
Found: C, 72.35; H; 7.99; N, 4.44.
EA: Anal. Calc for C19H25NO3: C, 72.35; H, 7.99; N, 4.44. Found:
C, 72.32 H; 8.04; N, 4.45.
HPLC: Brownlee 25 cm ꢀ 4.6 mm silica gel column; 30%
isopropanol/70% hexane; 1mL/min; ret. time 5.78min; purity X
99.9%.
HPLC: Brownlee 25 cm ꢀ 4.6 mm silica gel column; 30%
isopropanol/70% hexane; 1 mL/min; ret. time 12.87 min; purity
499.5%.
Scheme 1.
Copyright r 2011 John Wiley & Sons, Ltd.
J. Label Compd. Radiopharm 2011, 54 367–370