786
S. I. Kim et al.
water and made basic with NH4OH (100 mL), and the (20 mL) was added phenylhydrazine-HCl (102 mg,
precipitate was collected as a crude product which was 0.71 mmol, 1.5 equiv.) to yield white solids (105 mg,
1
recrystallized from EtOH to give
4
as white needles: 66%), whose H-NMR showed a set of proton reson-
mp 106-107oC [mp 107oC (Jahng et al., 2008)]. H- ances for two isomers (99%): H-NMR (250 MHz,
NMR (250 MHz, DMSO-d6 8.11 (d, 1H, = 2.3 Hz, CDCl3) ( -isomer, major) 11.03 (s, NH), 8.18 (d, 1H,
H1), 7.95 (dd, 1H, = 8.8, 2.3 Hz, H3), 7.85 (d, 1H, = 8.6 Hz, H-1), 7.91 (d, 1H, = 1.8 Hz, H-4), 7.69-
= 8.8 Hz, H4), 3.94 (t, 2H, = 6.2 Hz), 3.13 (t, 2H, 7.62 (m, 3H), 7.46-7.28 (m, 2H), 7.06 (t, 1H,
6.2 Hz), 1.95 (quintet, 2H,
2H, = 6.2 Hz).
1
1
)
δ
J
E
δ
J
J
J
J
J
J
J
=
J
= 7.3
= 6.2 Hz), 1.85 (quintet, Hz, H-4'), 4.22 (t, 2H,
Hz), 2.12 (m, 2H). (
8.25 (d, 1H,
H-2), 7.63-7.54 (m, 2H), 7.45-7.26 (m, 3H), 6.94 (t, 1H,
J
= 5.9 Hz), 2.79 (t, 2H, J = 6.4
J
Z-isomer, minor)
δ
14.25 (s, NH),
J
= 1.9 Hz, H-4), 8.13 (d, 1H, J = 8.6 Hz,
6-Benzylidene-2-chloro-6,7,8,9-tetrahydro-11H-
pyrido[2,1-b]quinazolinon-11-one
A mixture of (930 mg, 3.96 mmol) and benzaldehyde
(10 mL) in Ac2O (20 mL) was refluxed for 48 h. Excess
benzaldehyde and Ac2O was removed under reduced 3-Chlororutaecapine
pressure. To the residue was added water (100 mL). The mixture of ( )- and (
(
5
)
J
J
= 7.3 Hz, H-4'), 3.96 (t, 2H,
= 6.4 Hz), 2.35 (m, 2H).
J = 5.9 Hz), 2.79 (t, 2H,
4
(8)
E
Z)-isomers of
7
(60 mg, 0.18
Mixture was made basic with 50% aq. NaOH and ex- mmol) was dissolved in PPA (5 mL) and heated at
tracted with CH2Cl2 (50 mL × 3). The organic layers 180oC for 1.5 h to yield white needles (50 mg, 88%): mp
were washed with water, and dried over MgSO4. Eva- 321-322oC [lit. mp 314-316oC (Bergman and Bergman,
poration of the solvent afforded an oily material which 1985); lit. mp 320-322oC (Chen et al., 2009)]. 1H-NMR
was chromatographed on silica gel, eluting with CH2Cl2 (250 MHz, DMSO-d6
to give the desired product (0.94 g, 75%) which was 8.6 Hz, H-4), 7.65 (d, 1H,
recrystallized from EtOH to give white needles: mp 1H, = 1.8 Hz, H-4), 7.52-7.47 (m, 2H, H-2 & H-9),
)
δ
11.88 (s, NH), 8.14 (d, 1H,
J =
J
= 8.6 Hz, H-12), 8.63 (d,
J
1
148oC. H-NMR (250 MHz, CDCl3)
8.17 (d, 1H, = 8.6 Hz), 7.70 (d, 1H,
7.50-7.43 (m, 4H), 7.39-7.32 (m, 1H), 4.13 (t, 2H,
Hz), 2.95 (t, 2H, = 6.4 Hz), 2.05 (quintet, 2H,
Hz). 13C-NMR (62.5 MHz, DMSO-d6
δ
8.24 (br s, 1H), 7.27 (td, 1H,
J
= 7.3, 0.8 Hz, H-10), 7.09 (t, 2H,
= 6.8 Hz), 3.18 (t, 2H,
= 5.9 Hz). 13C NMR (62.5 MHz, DMSO-d6
J
J
= 7.3
= 6.8
J
J
= 1.9 Hz, H3), Hz, H-11), 4.43 (t, 2H, J
J
J
)
δ
160.32, 148.79,
J
= 6.2 146.82, 139.15, 139.04, 128.96, 126.99, 126.35, 125.55,
)
δ
161.45, 152.70, 125.29, 125.03, 120.35, 120.09, 119.76, 118.86, 112.87,
148.27, 140.03, 135.96, 135.85, 129.88, 129.48, 128.29, 41.13, 19.09.
127.96, 126.52, 118.34, 42.22, 25.47, 21.73.
RESULTS AND DISCUSSION
2-Chloro-6,7,8,9-tetrahydro-11H-pyrido[2,1-b]qui-
nazoline-6, 11-dione (6)
Rutaecarpine (1a R = H) (Lee et al., 2001) and its
A solution of
5 (500 mg, 2.13 mmol) in CH2Cl2 (50 derivatives with a substituent on ring A (1b R = 9-F;
mL) was cooled in acetone-dry ice bath and ozone was 1c R = 10-F; 1d R = 11-F; 1e R = 12-F; 1f R = 9-Cl; 1g
bubbled through the solution until the solution turns R = 10-Cl; 1h R = 11-Cl; 1i R = 12-Cl; 1j R = 9-Br; 1k
blue. Excess ozone was purged out and (CH3)2S (10 R = 10-Br; 1l R = 11-Br; 1m R = 12-Br; 1n R = 9-CH3;
mL) was added into the mixture. Evaporation of the 1o R = 10-CH3; 1p R = 11-CH3; 1q R = 12-CH3) (Lee
solvent afforded semisolid (0.65 g) which was chroma- et al., 2005) were prepared by employing previously
tographed on silica gel, eluting with CH2Cl2. The early reported methods in which Fischer indole synthesis
eluent gave the desired product as semisolid (536 mg, was employed as a key reaction.
1
78%). H-NMR (250 MHz, CDCl3)
δ
8.16 (dd, 1H,
J =
8.6 Hz, H-1), 7.91 (d, 1H,
1H, = 8.5, 2.0 Hz, H-2), 4.13 (t, 2H,
(t, 2H, = 6.4 Hz), 2.25 (quintet, 2H,
NMR (62.5 MHz, DMSO-d6
J = 2.0 Hz, H-4), 7.67 (dd,
J
J
J
= 5.9 Hz), 2.80
= 6.2 Hz). 13C-
J
)
δ
190.25, 160.36, 147.45,
146.51, 139.45, 129.00, 128.47, 120.54, 42.13, 36.98,
19.78. Anal. Calcd for C12H9ClN2O2: C, 57.96; H, 3.65;
N, 11.27. Found: C, 58.05; H, 3.70; N, 11.31.
Although a couple of synthetic procedures for the
preparation of 3-chlororutaecarpine have been reported
a few cases in the literature (Bergman and Bergman,
1985; Hamid et al., 2006; Chen et al., 2009; Lee et al.,
6-Phenylhydrazono-2-chloro-6,7,8,9-tetrahydro-
11H-pyrido-[2,1-b]quinazoline-6,11-dione (7)
To a solution of
6
(100 mg, 0.47 mmol) in 95% EtOH 2009), a detailed synthetic procedure for 3-chlororutae-