Notes
J . Org. Chem., Vol. 62, No. 12, 1997 4167
(CHCl3) 3382, 3020, 1604, 1510 cm-1; 250 MHz 1H NMR (CDCl3)
1.00 (d, 3H, J ) 6.8 Hz), 2.18 (m, 1H), 3.02 (dd, 1H, J ) 12.9,
6.4 HZ), 3.23 (m, 1H), 3.57 (dd, 1H, J ) 13.3, 6.2 Hz), 3.69 (m,
2H), 6.51 (dd, 1H, J ) 8.6, 7.6 Hz), 6.65 (ddd, 1H, J ) 7.4, 1.4,
0.6 Hz), 7.61 (dd, 1H, J ) 8.6, 1.4 Hz), 7.89 (bs, 1H); 100.6 MHz
13C NMR (CDCl3) 17.1, 32.8, 49.9, 51.8, 116.9, 117.9, 121.9, 135.4,
139.9, 142.1; HRMS (EI) for C10H13N3O2 (M+) calcd 207.1005,
found 207.1010.
to a brownish solid. Silica gel column chromatography with a
15-40% EtOAc in hexanes gradient afforded 60 mg (52%) of a
white solid. 10: mp 193-194 °C; IR (CHCl3) 3250, 3019, 2965,
1652, 1612 cm-1; 250 MHz 1H NMR (CDCl3) 1.16 (d, 3H, J )
6.9 Hz), 1.82 (s, 3H), 2.10 (s, 3H), 2.72 (m, 1H), 4.37 (bs, 4H),
5.90 (s, 1H), 6.93 (bd, 1H, J ) 5.9 Hz), 7.11 (m, 2H), 11.09 (bs,
1H); 100.6 MHz 13C NMR (CDCl3) 17.7, 20.4, 27.3, 32.5, 48.9,
53.1, 107.7, 116.7, 120.2, 123.5, 128.3, 128.6, 131.3, 153.3, 166.5,
169.2; HRMS (FAB) for C16H19N3SO (M+ + H) calcd 302.1327,
found 302.1341.
TIBO An a log 9. To a solution of 75 mg (0.36 mmol) of
nitrobenzodiazepine 14 in 10 mL of EtOH was added 70 mg of
10% Pd on carbon, and the reaction vessel was flushed with H2
at atmospheric pressure. After 50 min the catalyst was removed
by filtration under argon, and 182 mg (2.17 mmol) of NaHCO3
and 83 mg (65 µL, 1.1 mmol) of CS2 were added to the filtrate.
After 16 h at 37 °C the suspension was filtered and the solvent
was evaporated. The residual yellow solid was titurated with
Et2O (5 × 1 mL) and then subjected to chromatograpy on a silica
gel column with a 2/5/10% MeOH in CHCl3 gradient. This
afforded 36 mg (45%) of a yellow solid. 9: mp 255 °C (dec); IR
N-P r en ylben zod ia zep in e 16. To a slurry of 300 mg (1.4
mmol) of compound 14 and 1.0 g (7.3 mmol) of K2CO3 in 10 mL
of DMF was added 650 mg (4.4 mmol, 0.5 mL) of prenyl bromide
at room temperature. After 8 h, the reaction mixture was poured
into H2O and extracted with CH2Cl2 (5 × 15 mL). The organic
layer was dried over Na2SO4 and concentrated to a black residue.
Preparative TLC chromatography on silica gel with 15% EtOAc
in hexanes resulted in 370 mg (93%) of a black solid. 15: mp
64-65 °C; IR (CH2Cl2) 3358, 3051, 1595, 1527, 1503 cm-1; 250
MHz 1H NMR (CDCl3) 0.99 (d, 3H, J ) 6.8 Hz), 1.71 (s, 3H),
1.78 (s, 3H), 2.15 (m, 1H), 3.04 (dd, 1H, J ) 13.8, 8.0 Hz), 3.35
(m, 2H), 3.75 (m, 3H), 5.23 (bt, 1H), 6.53 (t, 1H, J ) 8.2 Hz),
6.73 (bs, 1H), 7.61 (d, 1H, J ) 8.9 Hz), 8.30 (bs, 1H); 100.6 MHz
13C NMR (CDCl3) 16.9, 18.1, 25.8, 31.9, 49.5, 51.6, 56.9, 116.3,
117.5, 120.5, 121.1, 134.2, 135.4, 142.4, 143.5; HRMS (EI) for
1
(KBr pellet) 3331, 3113, 1624 cm-1; 250 MHz H NMR (CDCl3)
1.12 (d, 3H, J ) 7.1 Hz), 2.38 (m, 1H), 3.24 (dd, 1H, J ) 13.1,
8.1 Hz), 3.41 (distorted d, 1H, J ) 13.9 Hz), 3.82 (dd, 1H, J )
13.9, 9.1 Hz), 4.32 (bs, 1H), 4.53 (dd, 1H, J ) 12.9, 1.9 Hz), 6.41
(d, 1H, J ) 8.1 Hz), 6.60 (d, 1H, J ) 7.8 Hz), 6.99 (t, 1H, J ) 7.9
Hz), 9.40 (s, 1H); 100.6 MHz 13C NMR (DMSO-d6) 16.1, 34.1,
51.5, 54.7, 97.1, 107.8, 119.5, 123.5, 132.5, 134.8, 166.7; HRMS
(EI) for C11H13N3S (M+) calcd 219.0830, found 219.0843.
C
15H21N3O2 (M+) calcd 275.1634, found 275.1634.
TIBO An a log 2. To a solution of 111 mg (0.40 mmol) of
Nitr oben zod ia zep in e 15. To a suspension of 150 mg (0.72
mmol) of compound 14, 244 mg (2.90 mmol) of solid NaHCO3,
and a catalytic amount of DMAP was added 258 mg (0.24 mL,
2.18 mmol) of 3,3-dimethylacryloyl chloride. After 3 h, the
reaction mixture was poured into aqueous saturated NaHCO3.
The aqueous layer was extracted with CH2Cl2 (3 × 15 mL) and
the combined organic layer was dried over Na2SO4. The solvent
was evaporated to leave a bright orange residue. Silica gel
column chromatography with 2% MeOH in CHCl3 resulted in
204 mg (98%) of a bright orange oil. 15: IR (CHCl3) 3370, 3014,
1645, 1624 cm-1; 250 MHz 1H NMR (CDCl3) 0.70 × 3H), 2.42
(m, 0.30 × 1H), 2.61 (m, 0.70 × 1H), 2.80 (dd, 0.70 × 1H, J )
13.3, 10.5 Hz), 2.98 (dd, 0.70 × 1H, J )14.5, 7.3 Hz), 3.19 (m,
0.30 × 1H), 3.35 (dd, 0.30 × 1H, J ) 13.4, 7.1 Hz), 3.60 (apparent
t, 0.30 × 1H), 3.87 (dt, 0.7H, J ) 13.8, 3.7 Hz), 4.56 (dd, 0.30 ×
1H, J ) 13.4, 6.7 Hz), 4.68 (dd, 0.70 × 1H, J ) 13.4, 7.2 Hz),
5.47 (bs, 0.30 × 1H), 5.78 (s, 0.70 × 1H), 6.59 (t, 1H, J ) 7.7
Hz), 7.09 (distorted t, presumably two closely situated d), 8.05
(distorted t, presumably two closely situated d, 1H), 8.30 (bs,
0.70 × 1H), 8.38 (bs, 0.30 × 1H); 100.6 MHz 13C NMR (CDCl3)
16.1, 18.1, 20.3, 27.2, 27.3, 32.0, 34.5, 48.1, 49.0, 51.1, 52.2, 115.0,
115.1, 116.9, 117.1, 125.2, 126.3, 131.3, 133.0, 134.0, 134.3, 135.0,
136.2, 143.1, 143.6, 152.4, 152.9, 166.2, 167.8; HRMS (CI) for
prenylnitrobenzodiazepine 16 in 10 mL of EtOH were added 18
mg of PtO2 and 330 mg (2.40 mmol) of K2CO3. The reaction
vessel was then flushed with H2 at atmospheric pressure. After
20 min, the solids were removed by filtration under argon, and
168 mg (0.20 mmol) of NaHCO3 and 91 mg (1.20 mmol, 72 µL)
of CS2 were added to the filtrate. After 16 h at 37 °C the filtrate
was concentrated to a beige solid. Silica gel column chroma-
tography with a 5/15/40 EtOAc in hexanes gradient afforded in
61 mg (53%) of an off-white solid. 2: mp 173-174 °C; IR (KBr
pellet) 3111, 3039, 1618, 1597, 1524 cm-1; 250 MHz 1H NMR
(CDCl3) 1.11 (d, 3H, J ) 7.0 Hz), 1.72 (s, 3H), 1.78 (s, 3H), 2.38
(m, 1H), 3.17 (dd, 1H, J ) 13.8, 7.7 Hz), 3.38 (dd, 1H, J ) 13.4,
2.7), 3.92 (m, 3 H), 4.56 (dd, 1H, J ) 13.7, 4.0 Hz), 5.28 (bt, 1H),
6.47 (d, 1H, J ) 8.2 Hz), 6.68 (d, 1H, J ) 7.8 Hz), 7.05 (t, 1H, J
) 8.0), 10.51 (s, 1H); 100.6 MHz 13C NMR (CDCl3) 17.3, 18.1,
25.7, 33.5, 51.3, 53.7, 60.1, 99.9, 107.9, 120.4, 122.7, 124.3, 131.8,
135.6, 136.9, 166.6; HRMS (EI) for
287.1456, found 287.1459.
C
16H21N3S (M+) calcd
Ack n ow led gm en t. We are indebted to Professor
Ellie Abashunab of the University of Rhode Island for
essential discussions and to the National Institutes of
Health (AI-29900) for financial support.
C
15H19O3N3 (M+ + H): calcd 290.1501, found 290.1483.
TIBO An a log 10. To a solution of 110 mg (0.38 mmol) of
Su p p or tin g In for m a tion Ava ila ble: IR, 1H, and 13C
spectra for compounds 2, 4a , 4b, 7-10, and 12-16 (37 pages).
This material is contained in libraries on microfiche, im-
mediately follows this article in the microfilm version of the
journal, and can be ordered from the ACS; see any current
masthead page for ordering information.
nitrodiazepine 15 in 10 mL of EtOH was added 80 mg of 10%
Pd on carbon and then the reaction vessel was flushed with H2
at atmospheric pressure. After 1 h, the catalyst was removed
by filtation under argon, and 130 mg (1.55 mmol) of NaHCO3
and 86 mg (1.13 mmol, 68 µL) of CS2 were added to the filtrate.
After 16 h at 37 °C the reaction mixture was poured into H2O.
The aqueous layer was extracted with EtOAc (5 × 15 mL). The
combined organic layer was dried over Na2SO4 and concentrated
J O962050L