S.U. Dighe, S. Batra / Tetrahedron 69 (2013) 9875e9885
9883
172e174 ꢀC; Rf¼0.74 (CH2Cl2eMeOH, 9.5:0.5, v/v); IR (KBr)
n
: 1713,
ESI-HRMS calculated for C23H20INO3 [MþNa]: 508.0386, found:
1586, 1232, 746 cmꢂ1. 1H NMR (300 MHz, CDCl3):
d
(ppm)¼3.42 (s,
508.0390.
3H, OCH3), 3.87 (s, 3H, OCH3), 5.88 (s, 1H, ArH), 6.95 (s, 1H, CH),
7.11e7.15 (m, 2H, ArH), 7.27e7.40 (m, 5H, ArH), 7.43 (s, 1H, ArH),
7.76 (dd, 1H, J1¼5.4 Hz, J2¼8.3 Hz, ArH); 13C NMR (75 MHz, CDCl3):
4.2.18. 4-Bromo-18-(cyclohex-1-en-1-yl)-17-iodo-13-methoxy-9-
oxa-1-azatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6,11,13,15,17-
heptaen-8-one (3dDc). Yield: 84% (0.94 g from 0.48 g) as a brown
solid, mp: 210e212 ꢀC; Rf¼0.64 (CH2Cl2eMeOH, 9.5:0.5, v/v); IR
d
(ppm)¼56.2, 56.3, 90.5, 107.6, 110.3, 114.7 (d, J¼22.5 Hz), 115.2,
118.8 (d, J¼22.5 Hz), 124.1 (d, J¼33.0 Hz), 128.6, 129.2, 129.9, 130.5,
130.6, 132.2, 132.3, 133.4 (d, J¼8.3 Hz), 138.8 (d, J¼51.0 Hz), 141.9,
147.6, 152.9, 160.3, 163.1, 163.6. MS (ESIþ): m/z¼530.0. ESI-HRMS
calculated for C24H17FINO4 [MH]þ: 530.0265, found: 530.00268.
(KBr)
CDCl3):
n .
: 1714, 1601, 1383, 1252, 836 cmꢂ1 1H NMR (300 MHz,
d
(ppm)¼1.38e1.56 (m, 6H, 3ꢁCH2), 1.71e1.86 (m, 2H, CH2),
3.80 (s, 3H, OCH3), 5.14 (s, 1H, ArH), 7.15 (s, 1H, CH), 7.24 (d, 1H,
J¼9.0 Hz, ArH), 7.44e7.62 (m, 3H, ArH), 7.76 (d, 1H, J¼9.0 Hz, ArH),
4.2.14. 13-Fluoro-17-iodo-18-(4-methylphenyl)-9-oxa-1-
azatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6,11,13,15,17-heptaen-8-
one (3cCa). Yield: 91% (0.88 g from 0.47 g); a white solid; mp:
7.95 (d, 1H, J¼9.0 Hz, ArH); 13C NMR (75 MHz, CDCl3):
d
(ppm)¼
21.4, 22.1, 25.3, 27.7, 56.1, 95.3, 111.2, 120.9, 124.5, 125.8, 128.6(2C),
131.1, 131.9(2C), 133.1(2C), 135.5, 136.7(2C), 143.3, 159.8, 163.8. MS
(ESIþ): m/z¼564.1. ESI-HRMS calculated for C23H19BrINO3 [MH]þ:
563.9671, found: 565.9653.
208e210 ꢀC; Rf¼0.66 (CH2Cl2eMeOH, 9.5:0.5, v/v); IR (KBr)
n
: 1724,
1593, 1237, 1114, 881 cmꢂ1. 1H NMR (300 MHz, CDCl3):
d
(ppm)¼
2.33 (s, 3H, CH3), 6.44 (d,1H, J¼8.2 Hz, ArH), 6.81 (s, 1H, CH), 6.95 (s,
2H, ArH), 7.08 (d, 2H, J¼7.9 Hz, ArH), 7.13e7.22 (m, 3H, ArH),
7.24e7.27 (m, 1H, ArH), 7.74 (dd,1H, J1¼5.2 Hz, J2¼8.8 Hz, ArH), 8.06
(dd, 1H, J1¼2.1 Hz, J2¼7.6 Hz, ArH); 13C NMR (75 MHz, CDCl3):
4.3. General procedure for the iodine-mediated reaction of 2-
alkynylbenzaldehydes (1) and 2-aminobenzamides (4) as ex-
emplified by the preparation of 5aA1
d
(ppm)¼21.5, 87.9, 114.6 (d, J¼23.4 Hz), 118.4 (d, J¼21.7 Hz), 123.1,
123.7, 123.8, 124.7, 126.1, 129.2, 129.8 (2C), 130.0, 130.4, 133.3 (d,
J¼8.3 Hz), 133.4, 135.5, 139.2, 141.8, 144.1, 160.3, 163.2, 163.5. MS
(ESIþ): m/z¼484.2. ESI-HRMS calculated for C23H15FINO2 [MH]þ:
484.0210, found: 484.0200.
To a stirred solution of 1aA (0.42 g, 2.0 mmol), 41 (0.272 g,
2.0 mmol) in MeCN (15 mL) were added I2 (0.762 g, 3.0 mmol),
K2CO3 (0.414 g, 3.0 mmol) and anhydrous Na2SO4 (0.289 g,
2.0 mmol) at room temperature. The reaction was allowed to pro-
ceed at room temperature until complete consumption of starting
material as monitored by TLC (ca. 3 h). Thereafter saturated
Na2S2O3 aqueous solution was added; the solid precipitate was
filtered and dried to give 5aA1.
4.2.15. 4,13-Difluoro-17-iodo-18-(4-methylphenyl)-9-oxa-1-
azatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6,11,13,15,17-heptaen-8-
one (3cCb). Yield: 84% (0.84 g from 0.47 g) as a gray solid, mp:
135e137 ꢀC; Rf¼0.67 (CH2Cl2eMeOH, 9.5:0.5, v/v); IR (KBr)
n: 1717,
(ppm)¼2.35 (s, 3H,
1374, 1257 cmꢂ1. 1H NMR (300 MHz, CDCl3):
d
4.3.1. 13-Iodo-12-phenyl-6H-isoquinolino[2,1-a]quinazolin-6-one
(5aA1). Yield: 92% (0.83 g from 0.42 g) as a gray solid, mp:
CH3), 6.36 (d,1H, J¼9.3 Hz, ArH), 6.93e7.06 (m, 3H, ArH), 7.13 (d, 2H,
J¼7.3 Hz, ArH), 7.37e7.42 (m, 3H, ArH), 7.88 (dd, 1H, J1¼5.3 Hz,
J2¼8.2 Hz, ArH), 8.07 (t, 1H, J1¼5.2 Hz, ArH); 13C NMR (75 MHz,
200e202 ꢀC; Rf¼0.53 (hexaneseEtOAc, 7:3, v/v); IR (KBr)
n: 1687,
(ppm)¼7.02 (d,
1501, 1138, 756 cmꢂ1. 1H NMR (400 MHz, CDCl3):
d
CDCl3):
d
(ppm)¼21.4, 91.3, 112.5 (d, J¼24.7 Hz), 114.2, 114.5, 114.6,
1H, J¼8.6 Hz, ArH), 7.16 (t, 1H, J¼7.7 Hz, ArH), 7.33 (t, 1H, J¼7.4 Hz,
ArH) 7.41 (br s, 5H, ArH), 7.66 (t, 1H, J¼7.6 Hz, ArH), 7.83 (t, 1H,
J¼7.4 Hz, ArH), 8.07 (d, 1H, J¼8.2 Hz, ArH), 8.26 (d, 1H, J¼7.7 Hz,
ArH), 8.92 (d, 1H, J¼8.0 Hz, ArH); 13C NMR (100 MHz, CDCl3):
114.8, 114.9, 120.6 (d, J¼23.3 Hz), 124.4 (d, J¼9.0 Hz), 126.3 (d,
J¼27.7 Hz), 129.4, 130.2, 134.0, 134.1, 134.6, 139.4, 139.8, 160.4, 162.7,
163.7, 166.2, 171.3. MS (ESIþ): m/z¼502.2. ESI-HRMS calculated for
C
23H14F2INO2 [MH]þ: 502.0116, found: 502.0091.
d
(ppm)¼91.5, 121.9, 122.6, 126.3, 126.8, 127.5, 127.9, 128.7, 129.7,
129.8, 130.8, 131.5, 132.8, 134.3, 135.8, 139.3, 139.5, 139.8, 153.7. MS
(ESIþ): m/z¼449.1. ESI-HRMS calculated for C22H13N2O [MH]þ:
449.0151, found: 449.0157.
4.2.16. 13-Fluoro-17-iodo-6-methyl-18-(4-methylphenyl)-9-oxa-1-
azatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6,11,13,15,17-heptaen-8-
one (3cCi). Yield: 79% (0.78 g from 0.47 g) as a pale yellow solid,
mp: 144e146 ꢀC; Rf¼0.64 (CH2Cl2eMeOH, 9.5:0.5, v/v); IR (KBr)
n
:
4.3.2. 12-(4-tert-Butylphenyl)-13-iodo-6H-isoquinolino[2,1-a]quina-
zolin-6-one (5aB1). Yield: 88% (0.88 g 0.53 g) as a yellow solid; mp:
1719, 1473, 1258, 747 (CO2Me), 3441 (OH) cmꢂ1. 1H NMR (300 MHz,
CDCl3):
d
(ppm)¼2.38 (s, 3H, CH3), 2.75 (s, 3H, CH3), 6.38 (t, 1H,
220e222 ꢀC; Rf¼0.49 (hexaneseEtOAc, 7:3, v/v); IR (KBr)
n: 1683,
(ppm)¼1.34 (s, 9H,
J¼4.8 Hz, ArH), 6.76 (s,1H, CH), 6.99e7.32 (m, 8H, ArH), 7.77 (dd,1H,
1469, 1119 cmꢂ1. 1H NMR (300 MHz, CDCl3):
d
J1¼3.6 Hz, J2¼8.8 Hz, ArH); 13C NMR (75 MHz, CDCl3):
d
(ppm)¼21.5,
3ꢁCH3), 7.12 (dt, 1H, J1¼1.5 Hz, J2¼8.7 Hz, ArH), 7.09e7.15 (m, 1H,
ArH), 7.29e7.42 (m, 5H, ArH), 7.65 (t, 1H, J¼7.3 Hz, ArH), 7.79e785
(m, 1H, ArH), 8.07 (d, 1H, J¼8.1 Hz, ArH), 8.26 (dd, 1H, J1¼1.4 Hz,
J2¼7.8, Hz, ArH), 8.93 (d, 1H, J¼8.1 Hz, ArH); 13C NMR (75 MHz,
21.8, 88.6, 114.6 (d, J¼23.4 Hz), 118.6 (d, J¼21.0 Hz), 122.7, 122.8,
123.8, 128.7, 129.1, 129.4, 130.2, 131.6, 133.2, 133.3 (d, J¼8.2 Hz),
139.1, 142.2, 142.4, 144.6, 160.2, 162.7, 163.5. MS (ESIþ): m/z¼498.1.
ESI-HRMS calculated for C24H17FINO2 [MH]þ: 498.0366, found:
498.0371.
CDCl3):
d
(ppm)¼31.3(3C), 34.9, 91.2, 121.9, 122.5, 125.5(2C), 126.2,
126.7, 127.3, 127.8, 129.4, 130.5, 131.1(2C), 132.7, 134.2, 135.8, 136.4,
139.3, 139.9, 153.3, 153.6, 167.8. MS (ESIþ): m/z¼505.1. ESI-HRMS
calculated for C26H21IN2O [MH]þ: 505.0777, found: 505.0783.
4.2.17. 18-(Cyclohex-1-en-1-yl)-17-iodo-13-methoxy-9-oxa-1-
azatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6,11,13,15,17-heptaen-8-
one (3dDa). Yield: 83% (0.84 g from 0.48 g) as a brown solid, mp:
4.3.3. 12-(4-tert-Butylphenyl)-13-iodo-9-nitro-6H-isoquinolino[2,1-
a]quinazolin-6-one (5aB2). Yield: 90% (0.98 g from 0.53 g) as
a yellow solid, mp: 230e232 ꢀC; Rf¼0.46 (hexaneseEtOAc, 7:3, v/v);
180e182 ꢀC; Rf¼0.62 (CH2Cl2eMeOH, 9.5:0.5, v/v); IR (KBr)
n
: 1701,
1473, 1371, 1295, 757 cmꢂ1. 1H NMR (300 MHz, CDCl3):
d
(ppm)¼
1.51 (br s, 4H, 2ꢁCH2),1.92e2.24 (m, 4H, 2ꢁCH2), 3.56 (s, 3H, OCH3),
6.51 (s, 1H, ArH), 7.09 (d, 1H, J¼8.2 Hz, ArH), 7.17 (s, 1H, CH),
7.28e7.33 (m, 1H, ArH), 7.49 (s, 2H, ArH), 7.53 (d, 1H, J¼7.3 Hz, ArH),
7.66 (s, 1H, ArH), 8.12 (d, 1H, J¼7.5 Hz, ArH), 8.27 (d, 1H, J¼7.6 Hz,
IR (KBr) n
: 1692, 1456, 1213, 756 cmꢂ1. 1H NMR (300 MHz, CDCl3):
d
(ppm)¼1.35 (s, 9H, 3ꢁCH3), 7.19 (d, 1H, J¼9.4 Hz, ArH), 7.36 (d, 2H,
J¼8.4 Hz, ArH), 7.45 (d, 2H, J¼8.4 Hz, ArH), 7.69 (t, 1H, J¼7.4 Hz,
ArH), 7.85e7.95 (m, 2H, ArH), 8.11 (d, 1H, J¼8.1 Hz, ArH), 8.89 (d, 1H,
J¼7.6 Hz, ArH), 9.09 (d, 1H, J¼2.6 Hz, ArH); 13C NMR (75 MHz,
ArH); 13C NMR (75 MHz, CDCl3):
96.8, 111.4, 116.5, 119.8, 121.6, 122.7, 125.1, 125.2(2C), 125.8, 130.7,
d
(ppm)¼21.1, 21.8, 24.4, 26.5, 55.8,
CDCl3):
d
(ppm)¼31.4(3C), 35.3, 92.9, 122.9, 123.2, 123.6, 124.6,
131.1, 131.9, 132.9, 133.6, 135.8, 137.7, 161.5. MS (ESIþ): m/z¼486.1.
125.8, 126.1, 128.3(2C), 130.1, 131.1(2C), 133.1, 135.1, 135.8, 136.1,