(3.0 mL), and degassed water (0.2 mL) was heated in a sealed
tube at 85 °C for 24 h. After cooling to room temperature, the
mixture was evaporated and the products were extracted with
DCM. The extract was washed with water and brine, dried over
Na2SO4, and evaporated. The residue was purified by flash
chromatography over silica gel 60N (hexane–ethyl acetate = 4:1)
6.6 Hz, 0.5H), 4.92 (d, J = 6.6 Hz, 0.5H), 5.86 (d, J = 5.9 Hz,
0.5H), 5.91 (d, J = 7.3 Hz, 0.5H), 6.45 (s, 0.5H), 6.58 (s, 0.5H),
6.72 (s, 1H), 6.81–6.99 (m, 4H), 7.04 (s, 1H), 7.18 (s, 0.5H), 7.24
(s, 0.5H), 9.27 (d, J = 7.5 Hz, 1H). 13C NMR (100 MHz, CDCl3):
δ 21.7, 21.9, 22.0, 22.2, 50.8, 55.3, 55.6, 56.0, 71.0, 71.1, 71.2,
96.3, 98.9, 101.1, 105.6, 110.5, 110.7, 110.9, 111.5, 111.8, 112.0,
118.7, 118.9, 119.0, 119.2, 119.3, 119.7, 119.8, 123.5, 124.1,
124.4, 128.3, 128.4, 130.4, 132.0, 141.7, 141.7, 146.8, 147.0,
147.0, 147.5, 149.4, 149.9, 150.4, 162.5. HRDARTMS m/z.
Calcd for C37H40NO10 [(M+H)+]: 658.26522. Found: 658.26263.
to give 9a as
a pale yellow solid (51.8 mg, 94%).
Recrystallization from DCM–hexane gave a pale yellow needles.
Mp 186–187 °C. IR (KBr): 1688, 1473, 1379, 1256, 1226, 1190,
1
1114 cm–1. H NMR (400 MHz, CDCl3): δ 1.07 (d, J = 6.1 Hz,
1.5H), 1.20 (d, J = 6.1 Hz, 1.5H), 1.21 (d, J = 6.1 Hz, 1.5H), 1.27
(d, J = 6.1 Hz, 1.5H), 1.42 (d, J = 6.1 Hz, 6H), 3.30 (s, 3H), 3.42
(br s, 3H), 3.59 (s, 3H), 3.81 (s, 1.5H), 3.82 (s, 1.5H), 4.25 (sep, J
= 6.1 Hz, 0.5H), 4.33 (sep, J = 6.1 Hz, 0.5H), 4.66 (sep, J = 6.1
Hz, 1H), 4.86 (d, J = 6.9 Hz, 0.5H), 4.96 (d, J = 6.9 Hz, 0.5H),
4.99 (d, J = 6.9 Hz, 0.5H), 5.04 (d, J = 6.9 Hz, 0.5H), 6.75–6.89
(m, 4H), 6.93 (d, J = 7.6 Hz, 1H), 6.95–7.01 (m, 1H), 7.04 (s,
1H), 7.08 (d, J = 8.3 Hz, 1H), 7.11–7.21 (m, 2H), 9.30 (d, J = 7.6
Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 21.7, 21.8, 21.9, 21.9,
22.0, 22.2, 50.7, 55.3, 55.7, 56.0, 71.1, 71.1, 71.2, 95.1, 105.6,
110.6, 111.4, 111.7, 112.0, 112.8, 114.6, 117.4, 118.1, 118.2,
118.6, 119.0, 119.4, 119.8, 121.0, 121.2, 123.5, 123.9, 124.1,
124.2, 124.4, 128.2, 128.3, 128.4, 130.4, 131.4, 131.8, 132.3,
132.4, 146.9, 147.5, 148.5, 149.3, 149.9, 150.4, 155.6, 162.6.
HRDARTMS m/z. Calcd for C36H40NO8 [(M+H)+]: 614.27539.
Found: 614.27399.
4.2.2.4. Methyl 2-[4-benzyloxy-5-methoxy-2-
(methoxymethoxy)phenyl]-8-isopropoxy-1-(3-isopropoxy-4-
methoxyphenyl)-9-methoxy-pyrrolo[2,1-a]isoquinoline-3-
carboxylate (9d)
Under an argon atmosphere, a mixture of 7 (290 mg, 0.521
mmol), 8d (497 mg, 1.56 mmol), Pd(dba)2 (30.0 mg, 52.1 µmol),
dppf (28.9 mg, 52.1 µmol), Na2CO3 (365 mg, 3.44 mmol), DME
(12 mL), and degassed water (1.0 mL) was refluxed for 24 h.
After cooling to rt, the mixture was evaporated and the products
were extracted with DCM. The extract was washed with water
and brine, dried over Na2SO4, and evaporated. The residue was
purified by flash chromatography over silica gel 60N (hexane–
ethyl acetate = 3:1) to give 9d as a pale brown solid (302 mg,
77%). Recrystallization from DCM–hexane gave a pale brown
granules. Mp 56–57 °C. IR (KBr): 1683, 1509, 1436, 1374, 1260,
1215, 1121, 1024 cm–1. 1H NMR (400 MHz, CDCl3): δ 0.98–1.33
(m, 6H), 1.40–1.48 (m, 6H), 3.22 (br s, 3H), 3.43 (br s, 3H), 3.61
(br s, 6H), 3.84 (br s, 3H), 4.20–4.43 (m, 1H), 4.63–4.95 (m, 3H),
5.06–5.16 (m, 2H), 6.48–7.50 (m, 13H), 9.27 (d, J = 7.5 Hz, 1H).
13C NMR (100 MHz, CDCl3): δ 21.6, 21.9, 22.0, 22.2, 50.8, 55.3,
55.5, 56.1, 56.4, 71.1, 71.2, 96.5, 102.8, 104.3, 104.4, 105.5,
105.6, 110.4, 110.5, 111.5, 111.9, 112.0, 112.4, 112.8, 112.9,
115.3, 118.6, 119.0, 119.7, 123.2, 123.4, 123.4, 124.2, 124.7,
127.3, 127.6, 127.8, 128.1, 128.2, 128.4, 128.7, 130.3, 131.7,
137.1, 144.2, 147.5, 149.3, 149.6, 149.9, 162.6. HRDARTMS
m/z. Calcd for C44H48NO10 [(M+H)+]: 750.32782. Found:
750.32788.
4.2.2.2. Methyl 2-[4,5-dimethoxy-2-(methoxymethoxy)phenyl]-8-
isopropoxy-1-(3-isopropoxy-4-methoxyphenyl)-9-methoxy-
pyrrolo[2,1-a]isoquinoline-3-carboxylate (9b)
According to the procedure described for the preparation of
9a, 7 (50.0 mg, 89.9 µmol), 8b (32.7 mg, 0.135 mmol), Pd(dba)2
(5.2 mg, 9.0 µmol), and dppf (5.0 mg, 9.0 µmol) were reacted.
After purification by column chromatography over silica gel 60N
(hexane–ethyl acetate = 2:1), 9b was obtained as a pale brown
solid (54.4 mg, 90%). Recrystallization from DCM–hexane gave
a pale brown powder. Mp 72–73 °C. IR (KBr): 1683, 1438, 1372,
1
1214, 1188, 1122, 1019 cm–1. H NMR (400 MHz, CDCl3): δ
1.05–1.33 (m, 6H), 1.42 (d, J = 6.1 Hz, 6H), 3.28 (br s, 3H), 3.43
(s, 3H), 3.62 (br s, 3H), 3.66 (s, 3H), 3.84 (s, 3H), 3.85 (s, 3H),
4.31 (br s, 1H), 4.66 (sep, J = 6.1 Hz, 1H), 4.70–5.00 (m, 2H),
6.48–6.63 (m, 1H), 6.75 (br s, 1H), 6.77–7.03 (m, 5H), 7.22–7.30
(m, 1H), 9.28 (d, J = 7.6 Hz, 1H). 13C NMR (100 MHz, CDCl3):
δ 21.6, 21.9, 22.0, 22.2, 50.8, 55.3, 55.7, 55.9, 56.1, 71.0, 71.1,
71.3, 96.6, 96.7, 101.5, 102.4, 105.6, 110.5, 111.5, 112.0, 112.9,
114.7, 118.6, 119.1, 119.7, 120.7, 123.4, 123.4, 124.2, 128.6,
130.3, 131.8, 143.4, 144.1, 147.5, 148.5, 148.5, 148.8, 149.0,
149.3, 149.7, 149.9, 162.6. HRDARTMS m/z. Calcd for
C38H44NO10 [(M+H)+]: 674.29652. Found: 674.29513.
4.2.2.5. Methyl 2-[5-benzyloxy-4-methoxy-2-
(methoxymethoxy)phenyl]-8-isopropoxy-1-(3-isopropoxy-4-
methoxyphenyl)-9-methoxy-pyrrolo[2,1-a]isoquinoline-3-
carboxylate (9e)
According to the procedure described for the preparation of
9d, 7 (421 mg, 0.756 mmol), 8e (361 mg, 1.13 mmol), Pd(dba)2
(41.9 mg, 72.9 µmol), dppf (45.0 mg, 81.2 µmol), Na2CO3 (529
mg, 4.99 mmol), DME (30 mL), and degassed water (2.0 mL)
was reacted for 24 h. After purification by column
chromatography over silica gel 60N (hexane–ethyl acetate = 2:1),
9e was obtained as a pale brown solid (552 mg, 97%).
Recrystallization from DCM–hexane gave a pale brown granules.
Mp 53–54 °C. IR (KBr): 1683, 1437, 1374, 1259, 1217, 1122,
4.2.2.3. Methyl 8-isopropoxy-1-(3-isopropoxy-4-methoxyphenyl)-
9-methoxy-2-[6-(methoxymethoxy)-1,3-benzodioxol-5-
yl]pyrrolo[2,1-a]isoquinoline-3-carboxylate (9c)
1
1065 cm–1. H NMR (400 MHz, CDCl3): δ 1.10–1.22 (m, 3H),
1.25 (br d, J = 6.0 Hz, 3H), 1.42 (d, J = 6.0 Hz, 6H), 3.28 (s, 3H),
3.43 (s, 3H), 3.59 (br s, 3H), 3.82 (s, 3H), 3.84 (s, 3H), 4.31 (sep,
J = 6.0 Hz, 1H), 4.66 (sep, J = 6.0 Hz, 1H), 4.67–4.98 (m, 4H),
6.59 (br s, 1H), 6.68–6.89 (m, 4H), 6.91 (d, J = 7.6 Hz, 1H), 7.04
(s, 1H), 7.24 (s, 1H), 7.25–7.40 (m, 5H), 9.27 (d, J = 7.6 Hz, 1H).
13C NMR (100 MHz, CDCl3): δ 21.7, 21.9, 22.0, 22.2, 50.8, 55.3,
55.6, 56.0, 71.0, 71.1, 71.2, 71.9, 96.4, 101.7, 105.6, 110.5,
111.5, 111.8, 112.0, 112.8, 118.1, 118.7, 119.0, 119.7, 123.4,
124.2, 127.4, 127.7, 128.4, 128.5, 130.3, 131.8, 137.4, 142.6,
147.0, 147.5, 149.3, 149.4, 149.9, 150.2, 162.6. HRDARTMS
m/z. Calcd for C44H48NO10 [(M+H)+]: 750.32782. Found:
750.32836.
According to the procedure described for the preparation of
9a, 7 (50.0 mg, 89.9 µmol), 8c (30.5 mg, 0.135 mmol), Pd(dba)2
(5.2 mg, 9.0 µmol), and dppf (5.0 mg, 9.0 µmol) were reacted.
After purification by column chromatography over silica gel 60N
(hexane–ethyl acetate = 3:1), 9c was obtained as a pale brown
solid (55.3 mg, 94%). Recrystallization from DCM–hexane gave
a pale brown powder. Mp 200–201 °C. IR (KBr): 1670, 1438,
1
1379, 1256, 1161, 1112 cm–1. H NMR (400 MHz, CDCl3): δ
1.15 (d, J = 6.0 Hz, 1.5H), 1.24 (d, J = 6.0 Hz, 1.5H), 1.25 (d, J =
6.0 Hz, 1.5H), 1.29 (d, J = 6.0 Hz, 1.5H), 1.42 (d, J = 6.0 Hz,
6H), 3.26 (s, 1.5H), 3.28 (s, 1.5H), 3.42 (s, 1.5H), 3.43 (s, 1.5H),
3.66 (s, 3H), 3.83 (s, 1.5H), 3.85 (s, 1.5H), 4.32 (sep, J = 6.0 Hz,
0.5H), 4.38 (sep, J = 6.0 Hz, 0.5H), 4.66 (sep, J = 6.0 Hz, 1H),
4.69 (d, J = 6.6 Hz, 0.5H), 4.83 (d, J = 6.6 Hz, 0.5H), 4.84 (d, J =