The Journal of Organic Chemistry
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NMR (150 MHz, DMSO-d6) δ 186.7 (CO), 155.7 (indole-C5),
145.6 (indole-C2), 132.2 (Ph-C1), 130.5 (indole-C7a), 129.7 (Ph-C2,
C2′, C4), 128.6 (Ph-C3, C3′), 127.8 (indole-C3a), 113.0 (indole-C6),
112.6 (indole-C7), 111.6 (indole-C3), 103.2 (indole-C4), 55.3 (CH3),
g, 72%) as an off-white solid: TLC Rf = 0.4 (30% EtOAc in n-heptane,
v/v); HPLC tR = 6.68 min (A); IR (neat) νmax = 3214, 1632, 1611,
1432, 1099; 1H NMR (600 MHz, DMSO-d6) δ 12.33 (br s, 1H; NH),
8.15 (ddd, J = 8.5, 2, 1 Hz, 1H; indole-H4), 7.75−7.71 (m, 2H; Ph-H2,
H2′), 7.46 (ddd, J = 8, 2, 1 Hz, 1H; indole-H7), 7.44−7.40 (m, 2H;
+
47.9 (CH2); HRMS (ESI+) m/z [M + H]+ Calcd for C17H15ClNO2
300.0786, found 300.0769.
Ph-H3, H3′), 7.29−7.23 (m, 2H; indole-H5, H6), 4.38 (s, 2H; CH2);
1
2-Chloro-1-(6-phenyl-5H-[1,3]dioxolo[4,5-f ]indol-7-yl)-
ethanone (8g). Synthesized according to GP-Acylation using a 20
mL microwave vial, 6-phenyl-5H-[1,3]dioxolo[4,5-f ]indole (0.230 g,
0.97 mmol), DCE (3.0 mL), DBU (0.174 mL, 1.16 mmol), and
chloroacetyl chloride (0.085 mL, 1.07 mmol). The solution was stirred
for 24 h. Purification by column chromatography (30% n-heptane in
CH2Cl2, v/v) gave an orange solid, which was washed with cold
EtOAc (10 mL) to yield indole 8g (0.24 g, 80%) as a yellow solid:
TLC Rf = 0.3 (30% EtOAc in n-heptane, v/v); HPLC tR = 6.56 min
13C NMR (150 MHz, DMSO-d6) δ 186.7 (CO), 162.9 (d, JCF
=
=
246 Hz; CF), 144.3 (indole-C2), 135.6 (indole-C7a), 132.2 (d, 3JCF
8 Hz; Ph-C2, C2′), 128.5 (d, 4JCF = 3 Hz; Ph-C1), 126.7 (indole-C3a),
2
123.3, 122.2 (indole-C6, C5), 121.3 (indole-C4), 115.6 (d, JCF = 22
Hz; Ph-C3, C3′), 111.9 (indole-C7), 111.6, (indole-C3), 48.3 (CH2);
HRMS (ESI+) m/z [M + H]+ Calcd for C16H12ClFNO+ 288.0586,
found 288.0577.
2-Chloro-1-(2-(furan-2-yl)-1H-indol-3-yl)ethanone (8k). Syn-
thesized according to GP-Acylation using a 10 mL microwave vial,
indole 7k (0.090 g, 0.49 mmol), DCE (1.5 mL), DBU (0.088 mL, 0.59
mmol), and chloroacetyl chloride (0.043 mL, 0.54 mmol). The
solution was stirred for 3 h 15 min. Purification by column
chromatography (40% n-heptane in CH2Cl2, v/v) gave indole 8k
(0.088 g, 69%) as a yellow solid: TLC Rf = 0.25 (40% n-heptane in
CH2Cl2, v/v); HPLC tR = 6.56 min; IR (neat) νmax = 3222, 2988,
1610, 1582, 1410; 1H NMR (600 MHz, DMSO-d6) δ 12.50 (br s, 1H;
NH), 8.02 (dd, J = 2, 0.5 Hz, 1H; furan-H5), 7.97−7.96 (m, 1H;
indole-H4), 7.66 (dd, J = 3.5, 1 Hz, 1H; furan-H3), 7.53 (ddd, J = 8, 1,
0.5 Hz, 1H; indole-H7), 7.28 (ddd, J = 8, 7, 1 Hz, 1H; indole-H6),
7.24 (ddd, J = 8.5, 7, 1 Hz, 1H; indole-H5), 6.77 (dd, J = 3.5, 2 Hz,
1H; furan-H4), 4.92 (s, 2H; CH2); 13C NMR (150 MHz, DMSO-d6) δ
186.5 (CO), 145.1 (furan-C2), 144.9 (furan-C5), 135.8 (indole-
C7a), 133.6 (indole-C2), 125.8 (indole-C3a), 123.4 (indole-C6),
122.2 (indole-C5), 121.2 (indole-C4), 114.4 (furan-C3), 112.5 (furan-
C4), 112.3 (indole-C7), 110.2 (indole-C3), 49.4 (CH2); HRMS (ESI
+) m/z [M + H]+ Calcd for C14H11ClNO2+ 260.0473, found 260.0459.
2-Chloro-1-(2-(3-chloro-4-fluorophenyl)-1H-indol-3-yl)-
ethanone (8l). Synthesized according to GP-Acylation using 2-(3-
chloro-4-fluorophenyl)-1H-indole (0.246 g, 1.00 mmol), DCE (3.0
mL), DBU (0.18 mL, 1.2 mmol), and chloroacetyl chloride (0.087 mL,
1.1 mmol). The solution was stirred for 24 h. Purification by column
chromatography (Gradient; 33% n-heptane in CH2Cl2, v/v to 100%
CH2Cl2) gave indole 8l (0.23 g, 72%) as a light-yellow solid: TLC Rf =
0.2 (33% n-heptane in CH2Cl2, v/v); HPLC tR = 6.94 min (A); IR
1
(A); IR (neat) νmax = 3190, 1591, 1450, 1422, 1035. H NMR (600
MHz, DMSO-d6) δ 12.15 (br s, 1H; NH), 7.63−7.61 (m, 2H; Ph-H2,
H2′), 7.59 (d, J = 0.5 Hz, 1H; indole-H4), 7.58−7.55 (m, 3H; Ph-H3,
H3′, H4), 6.94 (d, J = 0.5 Hz, 1H; indole-H7), 6.03 (s, 2H; OCH2O),
4.26 (s, 2H; CH2); 13C NMR (150 MHz, DMSO-d6) δ 186.8 (CO),
145.1 (indole-C5), 144.4 (indole-C6), 143.6 (indole-C2), 132.2 (Ph-
C1), 130.5 (indole-C7a), 129.7 (Ph-C2, C2′), 129.6 (Ph-C4), 128.6
(Ph-C3, C3′), 121.0 (indole-C3a), 112.0 (indole-C3), 100.8
(OCH2O), 100.0 (indole-C4), 92.4 (indole-C7), 47.8 (CH2); LRMS
(ESI+) m/z found 314.0 [M + H]+. The analytical data is in agreement
with that previously reported by us.8
2-Chloro-1-(1-methyl-2-phenyl-1H-indol-3-yl)ethanone (8h).
Synthesized according to GP-Acylation using a 20 mL microwave vial,
1-methyl-2-phenylindole (0.207 g, 1.00 mmol), DCE (3 mL), DBU
(0.18 mL, 1.2 mmol), and chloroacetyl chloride (0.087 mL, 1.1
mmol). The solution was stirred for 20 h. Purification by column
chromatography (30% n-heptane in CH2Cl2, v/v) gave indole 8h (0.24
g, 84%) as a yellow solid: TLC Rf = 0.2 (30% n-heptane in CH2Cl2, v/
v); HPLC tR = 7.08 min (A); IR (neat) νmax = 3053, 2946, 1646, 1466,
1395; 1H NMR (400 MHz, DMSO-d6) δ 8.29 (ddd, J = 8, 1.5, 0.5 Hz,
1H; indole-H4), 7.67−7.58 (m, 6H; PhH, indole-H7), 7.36 (ddd, J =
8, 7, 1.5 Hz, 1H; indole-H6), 7.32 (ddd, J = 8, 7, 1.5 Hz, 1H; indole-
H5), 4.05 (s, 2H; CH2), 3.52 (s, 3H; CH3); 13C NMR (150 MHz,
DMSO-d6) δ 185.9 (CO), 146.7 (indole-C2), 136.6 (indole-C7a),
130.9 (Ph-C1), 130.3, 130.1, 128.9 (5 × Ph-CH), 126.1 (indole-C3a),
123.4 (indole-C6), 122.8 (indole-C5), 121.5 (indole-C4), 112.2
(indole-C3), 110.9 (indole-C7), 48.0 (CH2), 31.0 (CH3); HRMS
(ESI+) m/z [M + Na]+ Calcd for C17H14ClNNaO+ 306.0656, found
306.0664.
1
(neat) νmax = 3149, 2984, 1618, 1441; H NMR (400 MHz, DMSO-
d6) δ 12.40 (br s, 1H; NH), 8.13−8.11 (m, 1H; indole-H4), 7.96 (dd,
4JHF = 7 Hz, 4JHH = 2 Hz, 1H; aryl-H2), 7.71 (ddd, 3JHH = 9 Hz, 4JHF
=
5 Hz, 4JHH = 2 Hz, 1H; aryl-H6), 7.62 (dd, 3JHF = 9 Hz, 3JHH = 9 Hz;
1H; aryl-H5), 7.49−7.46 (m, 1H; indole-H7), 7.31−7.24 (m, 2H;
indole-H6, H5), 4.51 (s, 2H; CH2); 13C NMR (100 MHz, DMSO-d6)
δ 186.7 (CO), 157.9 (d, 1JCF = 248 Hz, aryl-C4), 142.5 (indole-C2),
2-Chloro-1-(2-(2-fluorophenyl)-1H-indol-3-yl)ethanone (8i).
Synthesized according to GP-Acylation using a 20 mL microwave
vial, indole 7i (0.211 g, 1.00 mmol), DCE (3 mL), DBU (0.18 mL, 1.2
mmol), and chloroacetyl chloride (0.88 mL, 1.1 mmol). The solution
was stirred for 22 h. Purification by column chromatography (30% n-
heptane in CH2Cl2, v/v) gave indole 8i (0.21 g, 73%) as an off-white
3
135.6 (indole-C7a), 132.0 (Aryl-C2), 131.0 (d, JCF = 8 Hz, aryl-C6),
4
129.8 (d, JCF = 4 Hz; aryl-C1), 126.4 (indole-C3a), 123.4 (indole-
2
C6), 122.3 (indole-C5), 121.4 (indole-C4), 119.6 (d, JCF = 18 Hz,
2
solid: TLC Rf = 0.25 (30% n-heptane in CH2Cl2, v/v); HPLC tR
=
aryl-C3), 117.0 (d, JCF = 21 Hz, aryl-C5), 112.0 (indole-C7), 111.7
1
(indole-C3), 48.6 (CH2); HRMS (ESI+) m/z [M + H]+ Calcd for
6.62 min; IR (neat) νmax = 3145, 2988, 1619, 1581, 1436; H NMR
(600 MHz, DMSO-d6) δ 12.46 (br s, 1H; NH), 8.15−8.13 (m, 1H;
indole-H4), 7.69−7.63 (m, 2H; aryl-H), 7.48 (ddd, J = 7, 1, 0.5 Hz,
1H; indole-H7), 7.46−7.43 (m, 1H; aryl-H3), 7.41 (dt, J = 8, 1 Hz,
1H; aryl-H), 7.29 (ddd, J = 8, 7, 1 Hz, 1H; indole-H6), 7.29 (ddd, J =
8, 7, 1 Hz, 1H; indole-H5), 4.44 (s, 2H; CH2); 13C NMR (150 MHz,
C16H11Cl2FNO+ 322.0196, found 322.0199.
2-Chloro-1-(2-(4-chlorophenyl)-1H-indol-3-yl)ethanone
(8m). Synthesized according to GP-Acylation using a 20 mL
microwave vial, 2-(4-chlorophenyl)-1H-indole (0.23 g, 1.01 mmol),
DCE (3.0 mL), DBU (0.18 mL, 1.21 mmol), and chloroacetyl chloride
(0.088 mL, 1.11 mmol). The solution was stirred for 19 h. Purification
by column chromatography (30% n-heptane in CH2Cl2, v/v) gave a
yellow solid (0.25 g), which was washed with cold EtOAc (10 mL) to
give indole 8m (0.24 g, 78%) as an off-white solid: TLC Rf = 0.45
(30% EtOAc in n-heptane, v/v); HPLC tR = 6.92 min.; IR (neat) νmax
1
DMSO-d6) δ 186.4 (CO), 159.4 (d, JCF = 246 Hz; CF), 138.1
(indole-C2), 135.8 (indole-C7a), 132.2 (d, J = 8 Hz), 132.1 (d, J = 2
Hz) (2 × aryl-CH), 126.2 (indole-C3a), 124.7 (d, J = 3 Hz, aryl-CH),
123.4 (indole-C6), 122.2 (indole-C5), 121.3 (indole-C4), 120.1 (d,
2JCF = 15 Hz, aryl-C1), 116.0 (d, 2JCF = 21 Hz, aryl-C3), 112.6 (indole-
C3), 112.0 (indole-C7), 48.0 (CH2); HRMS (ESI+) m/z [M + H]+
Calcd for C16H12ClFNO+ 288.0586, found 288.0587.
1
= 3398, 1634, 1434, 1090; H NMR (400 MHz, DMSO-d6) δ 12.36
(br s, 1H; NH), 8.14−8.12 (m, 1H; indole-H4), 7.72−7.68 (m, 2H;
Ph-H2, H2′), 7.66−7.63 (m, 2H; Ph-H3, H3′), 7.48−7.46 (m, 1H;
indole-H7), 7.30−7.23 (m, 2H; indole-H5, H6), 4.43 (s, 2H; CH2);
13C NMR (100 MHz, DMSO-d6) δ 186.8 (CO), 143.8 (indole-C2),
135.6 (indole-C7a), 134.6 (Ph-C4), 131.7 (Ph-C2, C2′), 130.9 (Ph-
C1), 128.6 (Ph-C3, C3′), 126.6 (indole-C3a), 123.3, 122.3 (indole-C6,
C5), 121.3 (indole-C4), 111.9 (indole-C7), 111.6 (indole-C3), 48.4
2-Chloro-1-(2-(4-fluorophenyl)indol-3-yl)ethanone (8j). Syn-
thesized according to GP-Acylation using a 20 mL microwave vial, 2-
(4-fluorophenyl)indole (0.220 g, 1.04 mmol), DCE (3.0 mL), DBU
(0.19 mL, 1.25 mmol), and chloroacetyl chloride (0.091 mL, 1.15
mmol). The solution was stirred for 24 h. Purification by column
chromatography (30% n-heptane in CH2Cl2, v/v) gave indole 8j (0.22
H
dx.doi.org/10.1021/jo502463d | J. Org. Chem. XXXX, XXX, XXX−XXX