Paper
Organic & Biomolecular Chemistry
435.9145; found, 435.19132. IR (NaCl): ν 3207 (w, N–H), 3267 123.1, 122.5, 122.2, 120.9, 119.0, 114.7, 63.7, 13.6 ppm. HRMS
(w, N–H), 2978 (w, C–H), 1734 (s, CvO), 1666 (s, CvO) cm−1 (ESI+): Calcd for C20H17N2O3 ([M + H]+) 333.12337; found,
.
7-Methylene-6-oxo-6,7-dihydrobenzo[b]azepino[4,5-b]indole 333.12402. IR (neat): ν 3192 (w, N–H), 3068 (w, N–H), 2970 (w,
9aa and N-(2-indol-2-yl-phenyl)-acrylamide 4aa. General pro- C–H), 2923 (w, C–H), 1737 (s, CvO), 1660 (s, CvO) cm−1
cedure for the N-cyclization–Heck reaction. To a solution of X-Ray: see ESI.†
.
5aa (32 mg, 1.122 mmol) in DMF (3 mL) were added
9-Bromo-7-methylene-6-oxo-6,7-dihydrobenzo[b]azepino[4,5-
PdCl2(PPh3)2 (4 mg, 0.006 mmol), KI (10 mg, 0.061 mmol), b]indole 9ac and N-(2-(5-bromo-indol-2-yl)-phenyl)-acrylamide
and MA (12 mg, 0.122 mmol) and the reaction was heated at 4ac. Following the general procedure for N-cyclization–Heck
100 °C for 3 hours, under an air atmosphere. The reaction was reaction, the reaction of acrylamide 5ac (32 mg, 0.094 mmol),
cooled down to 25 °C and a saturated aqueous solution of PdCl2(PPh3)2 (0.003 g, 0.005 mmol), KI (0.008 g, 0.047 mmol),
NaCl (25 mL) was added. The mixture was extracted with and MA (9 mg, 0.094 mmol) in DMF (2.3 mL) at 80 °C
EtOAc (3×), the combined organic layers were washed with afforded, after purification by column chromatography (silica
water (15 mL) and dried (Na2SO4), and the solvent was evapor- gel, 80 : 20 hexane–EtOAc), 15.8 mg (50%) of 9ac and 15.9 mg
ated. The residue was purified by flash chromatography to (50%) of 4ac as a white solid.
afford 17.4 mg (37%) of 9aa and 12.3 mg (40%) of 4aa.
Data for 4ac: m.p.: 200 °C (dec.) (CH2Cl2). 1H-NMR
Data for 4aa: m.p.: 180 °C (dec.) (CH2Cl2). 1H-NMR (400.16 MHz, DMSO-d6) δ 10.40 (s, 1H, NH), 7.80 (d, J = 2.0 Hz,
(400.16 MHz, DMSO-d6) δ 10.37 (s, 1H, NH), 7.79 (dd, J = 7.9, 1H, ArH), 7.77 (d, J = 8.0 Hz, 1H, ArH), 7.44 (dd, J = 8.6, 1.2 Hz,
1.5 Hz, 1H, ArH), 7.71 (d, J = 8.0 Hz, 1H, ArH), 7.48 (d, J = 1H, ArH), 7.41–7.22 (m, 4H, ArH), 6.12 (s, 1H, Csp2–H), 5.75 (s,
8.0 Hz, 1H, ArH), 7.36 (ddd, J = 8.3, 7.1, 1.5 Hz, 1H, ArH), 7.30 1H, Csp2–H) ppm. 13C-NMR (100.62 MHz, DMSO-d6) δ 170.5,
(dd, J = 8.2, 1.4 Hz, 1H, ArH), 7.24 (ddd, J = 8.2, 6.9, 1.3 Hz, 136.4, 135.1, 135.0, 133.8, 129.2, 127.8, 126.9, 125.5, 123.7,
2H, ArH), 7.12 (ddd, J = 8.1, 7.1, 1.1 Hz, 1H, ArH), 6.12 (d, J = 121.8, 121.4, 120.7, 120.7, 113.7, 112.6, 110.1 ppm. HRMS
1.7 Hz, 1H, Csp2–H), 5.74 (d, J = 1.7 Hz, 1H, Csp2–H) ppm. (ESI+): Calc. for C17H1279BrN2O ([M + H]+) 339.01275; found,
13C-NMR (100.62 MHz, DMSO-d6) δ 170.6, 137.7, 135.7, 134.7, 339.01264. IR (neat): ν 3256 (w, C–H), 3036 (w, C–H), 1648 (s,
132.4, 128.6, 126.6, 126.0, 123.6, 123.0, 121.6, 121.1, 120.5, CvO) cm−1
120.0, 118.6, 111.6, 110.7 ppm. HRMS (ESI+): Calcd for Data for 9ac: m.p.: 94–96 °C (CH2Cl2). 1H-NMR
.
C17H13N2O ([M + 1]+) 261.10224; found, 261.10233. IR (neat): ν (400.16 MHz, DMSO-d6) δ 9.96 (s, 1H, NH), 7.93 (d, J = 1.9 Hz,
3253 (s, CvH), 1644 (s, CvO) cm−1
.
1H, ArH), 7.87 (dd, J = 7.8, 1.3 Hz, 1H, ArH), 7.63 (d, J = 8.1 Hz,
1
Data for 9aa: H-NMR (400 MHz, CDCl3) δ 8.70 (s, 1H, NH), 1H, ArH), 7.59 (d, J = 8.7 Hz, 1H, ArH), 7.46 (m, 2H, ArH), 7.38
8.43 (d, J = 8.6 Hz, 1H, ArH), 8.06 (s, 1H, NH), 7.68 (dt, J = 7.9, (td, J = 7.7, 1.1 Hz, 1H, ArH), 6.53 (dd, J = 16.9, 10.2 Hz, 1H,
1.1 Hz, 1H, ArH), 7.49–7.40 (m, 2H, ArH), 7.36 (ddd, J = 8.7, H2), 6.26 (dd, J = 17.1, 1.9 Hz, 1H, H3trans), 5.80 (dd, J = 10.2,
7.5, 1.6 Hz, 1H, ArH), 7.27 (ddd, J = 8.2, 6.0, 1.3 Hz, 1H, ArH), 1.6 Hz, 1H, H3cis) ppm. 13C NMR (101 MHz, DMSO-d6) δ 163.7,
7.22–7.16 (m, 2H, ArH), 6.66 (dd, J = 2.1, 1.0 Hz, 1H, ArH), 6.34 154.3, 152.7, 151.8, 134.6, 131.6, 131.0, 129.5, 128.1, 127.2,
(dd, J = 16.9, 1.2 Hz, 1H, H2), 6.11 (dd, J = 16.9, 10.3 Hz, 1H, 127.2, 127.1, 126.1, 123.7, 115.4, 113.1, 104.5 ppm. MS (ESI+):
H3trans), 5.70 (dd, J = 10.2, 1.1 Hz, 1H, H3cis) ppm. 13C-NMR m/z (%) 343 ([M + H]+, 81Br), 341 ([M + H]+, 79Br). HRMS (ESI+):
(100.62 MHz, CDCl3) δ 163.9, 136.8, 135.2, 134.0, 131.3, 129.4, Calcd for C17H1479BrN2O ([M
+
H]+) 341.02840; found,
129.3, 128.8, 128.0, 124.7, 123.5, 122.9, 121.6, 120.8, 120.6, 341.02751. IR (neat): ν 3364 (s, N–H), 3265 (w, N–H), 1669
111.3, 102.6 ppm. MS (EI): m/z (%) 262 (M+, 3), 244 (83), 243 (s, CvO) cm−1
(100), 242 (34). HRMS (EI): Calcd for C17H14N2O 262.1106; Ethyl
.
(E)-4-(2-(1H-indol-2-yl)-phenylamino)-4-oxobut-2-
found, 262.1094. IR (neat): ν 3336 (m, N–H), 3209 (m, N–H), enoate 9ba. Following the general procedure for N-cyclization–
2975 (w, C–H), 2927 (w, C–H), 1649 (s, CvO) cm−1
Heck reaction, the reaction of compound 5ba (65 mg,
.
Ethyl 7-methylene-6-oxo-6,7-dihydrobenzo[2,3]azepino[4,5-b]- 0.194 mmol), PdCl2(PPh3)2 (0.007 g, 0.010 mmol), KI (0.016 g,
indole-12(5H)-carboxylate 4ab. Following the general pro- 0.097 mmol), and MA (19 mg, 0.194 mmol) in DMF (4.75 mL)
cedure for N-cyclization–Heck reaction, the reaction of acryl- at 100 °C afforded, after purification by column chromato-
amide 5ab (25 mg, 0.075 mmol), PdCl2(PPh3)2 (0.003 g, graphy (silica gel, 80 : 20 hexane–EtOAc), 45.1 mg (70%) of the
0.004 mmol), KI (0.006 g, 0.037 mmol), and MA (7 mg, title compound as a white solid. m.p.: 131 °C (CH2Cl2).
0.075 mmol) in DMF (1.8 mL) at 100 °C afforded, after purifi- 1H-NMR (400.16 MHz, CDCl3) δ 8.59 (s, 1H, NH), 8.46 (d, J =
cation by column chromatography (silica gel, 80 : 20 hexane– 8.3 Hz, 1H, ArH), 8.27 (s, 1H, NH), 7.70 (d, J = 7.9 Hz, 1H,
EtOAc), 13.0 mg (52%) of the title compound as a white solid. ArH), 7.56–7.40 (m, 2H, ArH), 7.38 (t, J = 8.1 Hz, 1H, ArH), 7.28
m.p.: 205–208 °C (CH2Cl2). 1H-NMR (400 MHz, DMSO-d6) δ (t, J = 8.1 Hz, 1H, ArH), 7.32–7.18 (m, 2H, ArH), 6.87 (app s,
10.37 (s, 1H, NH), 8.12 (d, J = 8.4 Hz, 1H, ArH), 7.72 (d, J = 7.8 2H, 2 × Csp2–H), 6.67 (d, J = 0.9 Hz, 1H, ArH), 4.23 (q, J =
Hz, 1H, ArH), 7.49–7.43 (m, 1H), 7.40 (d, J = 7.9 1H, ArH), 7.1 Hz, 2H, CH2), 1.30 (t, J = 7.1 Hz, 3H, CH3) ppm. 13C-NMR
7.39–7.33 (m, 2H), 7.28 (d, J = 7.3 Hz, 1H), 7.20–7.15 (m, 1H), (100.62 MHz, CDCl3) δ 165.3, 161.9, 136.8, 136.2, 134.8, 133.6,
6.20 (d, J = 1.1 Hz, 1H, Csp2–H), 5.87 (d, J = 1.1 Hz, 1H, Csp2– 131.9, 129.5, 129.3, 128.8, 125.2, 123.6, 123.1, 121.6, 121.0,
H), 4.31 (q, J = 7.1 Hz, 2H, CH2), 1.13 (t, J = 7.1 Hz, 3H, CH3) 120.8, 111.3, 102.8, 61.4, 14.2 ppm. MS (EI): m/z (%) 334 (M+,
ppm. 13C-NMR (100.62 MHz, DMSO-d6) δ 172.2, 151.0, 137.7, 12), 317 (25), 316 (94), 288 (38), 244 (23), 243 (100), 242 (79).
134.6, 134.0, 132.5, 129.8, 128.5, 126.6, 126.0, 124.5, 123.8, HRMS (EI): Calcd for C20H18N2O3 334.1317; found, 334.1325.
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