Pin et al.
1
4.10 (d, 1H, J ) 14.9 Hz, CH2N), 4.41 (t, 1H, J ) 4.7 Hz, CH),
4.95-5.01 (m, 2H, dCH2), 5.27-5.45 (m, 1H, J ) 7.7 Hz,
dCH), 5.36 (d, 1H, J ) 14.9 Hz, CH2N), 6.84 (d, 2H, J ) 8.6 Hz,
1593, 1494 cm-1; H NMR (CDCl3) δ 3.65 (s, 3H, OCH3), 3.73
(s, 3H, OCH3), 4.74 (d, 1H, J ) 7.3 Hz, CH2N), 5.54 (d, 1H, J )
7.3 Hz, CH2N), 5.81 (s, 1H, CH), 6.52 (d, 2H, J ) 8.6 Hz, Haro),
6.75 (d, 2H, J ) 8.6 Hz, Haro), 6.86 (d, 2H, J ) 8.6 Hz, Haro),
7.26-7.38 (m, 1H, Haro), 7.32 (d, 2H, J ) 8.6 Hz, Haro), 7.46-
7.64 (m, 3H, Haro); 13C NMR (CDCl3) δ 45.6 (CH2), 55.3 (OCH3),
55.5 (OCH3), 65.5 (CH), 114.4 (2CHaro), 114.9 (2CHaro), 118.0 (Cq),
123.6 (Cq), 123.6 (CHaro), 124.0 (CHaro), 128.8 (CHaro), 131.2 (Cq),
132.1 (CHaro), 134.6 (2CHaro), 137.4 (2CHaro), 143.1 (Cq), 159.9
(Cq), 160.7 (Cq), 167.0 (CdO). Anal. Calcd for C23H21NO3S2
(423.1): C, 65.22; H, 5.00; N, 3.31; O, 11.33. Found: C, 65.22;
H, 5.00; N, 3.31; O, 11.33.
Haro), 7.22 (d, 2H, J ) 8.6 Hz, Haro), 7.35-7.52 (m, 3H, Haro),
7.88 (d, 1H, J ) 6.3 Hz, Haro); 13C NMR (CDCl3) δ 35.2 (CH2),
43.3 (CH2), 55.4 (CH3), 57.9 (CH), 114.2 (2CHaro), 119.3 (CH2),
122.5 (CHaro), 123.8 (CHaro), 128.2 (CHaro), 129.2 (Cq), 129.6
(2CHaro), 131.4 (CHaro), 131.5 (CHaro), 132.5 (Cq), 145.0 (Cq), 159.1
(Cq), 168.5 (CdO). Anal. Calcd for C19H19NO2 (293.14): C, 77.79;
H, 6.53; N, 4.77. Found: C, 77.62; H, 6.41; N, 4.59.
7-Allyl-6,7-dihydro-6-(4-methoxybenzyl)-pyrrolo[3,4-b]pyri-
din-5-one (4g). To a stirred cold solution of 7-acetoxy-6,7-dihydro-
6-(4-methoxybenzyl)-5H-pyrrolo[3,4-b]pyridin-5-one (3g) (312 mg,
1 mmol) and allyltrimethylsilane (1.37 g, 1.2 equiv) in 10 mL of
anhydrous CH2Cl2 was added aluminum trichloride (99.99%, 4.0
g, 30 mmol) over a period of 10 min at -5 to 0 °C, and the mixture
was allowed to reach room temperature. After 3 h of reaction at
room temperature, the organic layer was carefully neutralized with
NaOH 2 N solution, separated, dried over MgSO4, and evaporated
to give after chromatograpic purification the title product 4g as a
yellow oil in 60% yield: Rf 0.42 (cyclohexane/AcOEt 1:4); IR ν
3-(2-Methoxycarbonylphenylthio)-2-((2-methoxycarbonylphe-
nylthio)methyl)-isoindolin-1-one (4o). This product was isolated
as a colorless oil: 43% yield; Rf 0.53 (cyclohexane/AcOEt 1:1);
IR (KBr) ν 1710, 1523, 1471, 1435 cm-1; H NMR (CDCl3) δ
1
3.88 (s, 3H, OCH3), 3.95 (s, 3H, OCH3), 4.76 (d, 1H, J ) 14.1 Hz,
CH2N), 5.84 (d, 1H, J ) 14.1 Hz, CH2N), 6.23 (s, 1H, CH), 7.14-
7.28 (m, 4H, Haro), 7.34-7.56 (m, 4H, Haro), 7.64-7.72 (m, 3H,
H
aro), 7.88 (dd, 1H, J ) 7.8 and 1.6 Hz, Haro); 13C NMR (CDCl3)
δ 42.5 (CH2), 52.4 (OCH3), 52.6 (OCH3), 65.1 (CH), 123.8 (CHaro),
124.1 (CHaro), 125.5 (CHaro), 127.8 (CHaro), 128.3 (CHaro), 129.1
(Cq), 129.2 (CHaro), 130.7 (CHaro), 131.1 (Cq), 131.4 (CHaro), 131.8
(CHaro), 132.5 (Cq), 132.6 (CHaro), 132.8 (CHaro), 133.0 (CHaro),
134.1 (Cq), 137.7 (Cq), 142.8 (Cq), 167.1 (CdO), 167.2 (CdO),
167.3 (CdO). Anal. Calcd for C25H21NO5S2 (479.09): C, 62.61;
H, 4.41; N, 2.92. Found: C, 62.50; H, 4.32; N, 2.79.
1
2984, 2953, 1685, 1611, 1514, 1474 cm-1; H NMR (CDCl3) δ
2.72-2.97 (m, 2H, CH2), 3.76 (s, 3H, OMe), 4.11 (d, 1H, J )
14.9 Hz, CH2N), 4.45 (dd, 1H, J ) 4.7 and 3.9 Hz, CH), 4.91 (d,
1H, J ) 10.2 Hz, dCH2), 4.98 (d, 1H, J ) 18.0 Hz, dCH2), 5.15-
5.27 (m, 1H, dCH), 5.36 (d, 1H, J ) 14.9 Hz, CH2N), 6.83 (d,
2H, J ) 8.6 Hz, Haro), 7.21 (d, 2H, J ) 8.6 Hz, Haro), 7.36 (dd, 1H,
J ) 7.8 and 4.7 Hz, Haro), 8.10 (d, 1H, J ) 7.8 Hz, Haro), 8.68 (d,
1H, J ) 4.7 Hz, Haro); 13C NMR (CDCl3) δ 33.8 (CH2), 43.5 (CH2),
55.5 (CH3), 59.6 (CH), 114.4 (2CHaro), 119.7 (CH2), 123.5 (CHaro),
126.5 (Cq), 128.8 (Cq), 129.7 (2CHaro), 130.8 (CHaro), 132.0 (CHaro),
152.5 (CHaro), 159.4 (Cq), 164.9 (Cq), 166.8 (CdO). Anal. Calcd
for C18H18N2O2 (294.14): C, 73.45; H, 6.16; N, 9.52. Found: C,
73.31; H, 6.08; N, 9.40.
5,6-Dihydro-2-methylpyrrolo[2,1-a]isoquinolin-3(2H)-one (4q).
This product was isolated as a white solid: 76% yield; Rf 0.35
(cyclohexane/AcOEt 3:2); mp 107-109 °C; IR (KBr) ν 3009, 2994,
1
1703, 1612 cm-1; H NMR (CDCl3) δ 1.34 (d, 3H, J ) 7.8 Hz,
CH3), 2.94 (t, 2H, J ) 6.3 Hz, CH2), 3.24 (qd, 1H, J ) 7.8 and 3.1
Hz, CH), 3.72 (t, 2H, J ) 6.3 Hz, NCH2), 5.64 (d, 1H, J ) 3.1 Hz,
dCH), 7.17-7.29 (m, 3H, Haro), 7.52-7.56 (m, 1H, Haro); 13C NMR
(CDCl3) δ 15.4 (CH3), 29.1 (CH2), 37.0 (CH2), 43.6 (CH), 104.0
(CHaro), 124.4 (CHaro), 127.2 (CHaro), 128.7 (CHaro), 129.0 (CHaro),
134.1 (2Cq), 138.3 (Cq), 180.0 (CdO). Anal. Calcd for C13H13NO
(199.1): C, 78.36; H, 6.58; N, 7.03. Found: C, 78.21; H, 6.43; N,
6.89.
3-Allyl-2,3-dihydro-2-(4-methoxybenzyl)-pyrrolo[3,4-b]quino-
lin-1-one (4h). This product was isolated as a yellow solid: 92%
yield; Rf 0.56 (cyclohexane/AcOEt 1:1); mp 97 °C; IR (KBr) ν
1
2981, 1684, 1634, 1513, 1467 cm-1; H NMR (CDCl3) δ 2.81-
3.08 (m, 2H, CH2), 3.76 (s, 3H, OCH3), 4.18 (d, 1H, J ) 14.9 Hz,
CH2N), 4.58 (dd, 1H, J ) 4.7 and 3.9 Hz, CH), 4.88 (d, 1H, J )
10.2 Hz, dCH2), 4.99 (d, 1H, J ) 17.2 Hz, dCH2), 5.19-5.36
(m, 1H, dCH), 4.43 (d, 1H, J ) 14.9 Hz, CH2N), 6.84 (d, 2H,
J ) 8.6 Hz, Haro), 7.25 (d, 2H, J ) 8.6 Hz, Haro), 7.60 (dd, 1H,
J ) 7.8 and 7.0 Hz, Haro), 7.83 (dd, 1H, J ) 8.6 and 7.0 Hz, Haro),
7.98 (d, 1H, J ) 7.8 Hz, Haro), 8.12 (d, 1H, J ) 8.6 Hz, Haro), 8.61
(s, 1H, Haro); 13C NMR (CDCl3) δ 34.4 (CH2), 43.7 (CH2), 55.5
(CH3), 59.8 (CH), 114.4 (2CHaro), 119.7 (CH2), 124.2 (Cq), 127.1
(CHaro), 127.8 (Cq), 128.7 (Cq), 129.4 (CHaro), 129.7 (CHaro), 129.8
(2CHaro), 131.1 (CHaro), 131.4 (CHaro), 132.6 (CHaro), 150.1 (Cq),
159.4 (Cq), 163.4 (Cq), 166.7 (CdO). Anal. Calcd for C22H20N2O2
(344.15): C, 76.72; H, 5.85; N, 8.13. Found: C, 76.58; H, 5.69;
N, 8.04.
2-(Furan-2-ylmethyl)-3-(2-oxopropyl)-isoindolin-1-one (5a).
This product was isolated as a brown solid: 71% yield; Rf 0.28
(cyclohexane/AcOEt 1:1); mp 100 °C; IR (KBr) ν 1718, 1687, 1471
cm-1; H NMR (CDCl3) δ 2.11 (s, 3H, CH3), 2.71 (dd, 1H, J )
1
17.2 and 7.0 Hz, CH2), 3.04 (dd, 1H, J ) 17.2 and 4.7 Hz, CH2),
4.51 (d, 1H, J ) 15.6 Hz, CH2N), 4.94 (d, 1H, J ) 15.6 Hz, CH2N),
5.03 (dd, J ) 7.0 and 4.7 Hz, 1H, CH), 6.25-6.31 (m, 2H, Hfur),
7.31 (s, 1H, Haro), 7.37-7.47 (m, 3H, Haro), 7.82 (d, 1H, J ) 7.1
Hz); 13C NMR (CDCl3) δ 30.8 (CH3), 37.7 (CH2), 46.6 (CH2), 55.8
(CH), 108.7 (CHaro), 110.8 (CHaro), 122.7 (CHaro), 124.1 (CHaro),
128.6 (CHaro), 131.8 (Cq), 132.1 (CHaro), 142.5 (CHaro), 145.8 (Cq),
150.6 (Cq), 168.3 (CdO), 205.8 (CdO). Anal. Calcd for C16H15-
NO3 (269.11): C, 71.36; H, 5.61; N, 5.20. Found: C, 71.22; H,
5.47; N, 5.06.
5-Allyl-1-(2-bromobenzyl)-pyrrolidin-2-one (4i). This product
was isolated as a colorless oil: 73% yield; Rf 0.33 (cyclohexane/
AcOEt 1:1); IR (KBr) ν 2929, 1676, 1441 cm-1; 1H NMR (CDCl3)
δ 1.70-1.87 (m, 1H, CH2), 1.99-2.24 (m, 2H, CH2), 2.29-2.58
(m, 3H, CH2), 3.53 (septuplet, 1H, J ) 3.9 Hz, CH), 4.27 (d, 1H,
J ) 15.6 Hz, CH2N), 4.90 (d, 1H, J ) 15.6 Hz, CH2N), 5.08 (d,
1H, J ) 13.1 Hz, dCH2), 5.08 (d, 1H, J ) 14.7 Hz, dCH2), 5.53-
5.74 (m, 1H, dCH), 7.06-7.18 (m, 1H, Haro), 7.22-7.28 (m, 2H,
2-(Furan-2-ylmethyl)-3-(2-oxophenethyl)-isoindolin-1-one (6a).
This product was isolated as a white solid: 84% yield; Rf 0.42
(cyclohexane/AcOEt 1:1); mp 104 °C; IR (KBr) ν 3684, 3620, 3019,
2400, 1686, 1523, 1427 cm-1; H NMR (CDCl3) δ 3.01 (dd, 1H,
1
J ) 18.0 and 7.0 Hz, CH2), 3.39 (dd, 1H, J ) 18.0 and 5.0 Hz,
CH2), 4.33 (d, 1H, J ) 15.6 Hz, CH2N), 4.80 (d, 1H, J ) 15.6 Hz,
CH2N), 5.07 (dd, 1H, J ) 7.0 and 5.0 Hz, CH), 5.98-6.05 (m,
2H, Hfur), 7.01 (s, 1H, Hfur), 7.16-7.28 (m, 5H, Haro), 7.33-7.41
(m, 1H, H
H
aro), 7.53 (d, 1H, J ) 7.8 Hz, Haro); 13C NMR (CDCl3) δ 23.5
(CH2), 30.1 (CH2), 37.6 (CH2), 44.3 (CH2), 57.0 (CH), 119.0 (CH2),
123.5 (Cq), 127.9 (CHaro), 129.2 (CHaro), 129.7 (CHaro), 132.8
(CHaro), 133.1 (CHaro), 136.0 (Cq), 175.6 (CdO). Anal. Calcd for
C14H16BrNO (293.04): C, 57.16; H, 5.48; N, 4.76. Found: C, 57.02;
H, 5.35; N, 4.59.
aro), 7.62-7.71 (m, 3H, Haro); 13C NMR (CDCl3) δ 37.7
(CH2), 42.2 (CH2), 56.3 (CH), 108.8 (CHaro), 110.7 (CHaro), 123.1
(CHaro), 124.0 (CHaro), 128.3 (2CHaro), 128.6 (CHaro), 129.0
(2CHaro), 131.8 (Cq), 132.0 (CHaro), 133.8 (CHaro), 136.6 (Cq), 142.5
(CHaro), 146.1 (Cq), 150.5 (Cq), 168.4 (CdO), 197.3 (CdO). Anal.
Calcd for C21H17NO3 (331.12): C, 76.12; H, 5.17; N, 4.23.
Found: C, 76.00; H, 5.05; N, 4.14.
3-(4-Methoxyphenylthio)-2-((4-methoxyphenylthio)methyl)-
isoindolin-1-one (4n). This product was isolated as a colorless
oil: 35% yield; Rf 0.60 (cyclohexane/AcOEt 1:1); IR (KBr) ν 1703,
1190 J. Org. Chem., Vol. 72, No. 4, 2007