PAPER
A Facile Synthetic Route towards Substituted Thieno[3,2-e]indoles
771
Ethyl 5-Acetamido-4-[(trimethylsilyl)ethynyl]benzo[b]thio-
phene-2-carboxylate (5b)
Yield: 86%; mp 152 °C.
IR: 3380, 2960, 2140, 1700 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.37 [s, 9 H, Si(CH3)3], 1.43 (t,
J = 7.3 Hz, 3 H, CH3), 2.26 (s, 3 H, CH3CO), 4.42 (q, J = 7.3 Hz, 2
H, CO2CH2), 7.78 (d, J = 9.1 Hz, 1 H), 8.05 (s, 1 H, NH), 8.15 (s, 1
H), 8.57 (d, J = 9.1 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 0.0, 14.3, 24.9, 61.8, 97.8, 107.2,
107.5, 119.1, 123.7, 129.5, 135.4, 136.8, 138.1, 139.2, 162.6, 168.2.
1H NMR (300 MHz, CDCl3): d = 1.42 (t, J = 7.3 Hz, 3 H, CH3),
1.84–1.59 (m, 6 H, THP), 2.27 (s, 3 H, CH3CO), 3.62 (m, 1 H,
THP), 3.96 (m, 1 H, THP), 4.42 (q, J = 7.3 Hz, 2 H, CO2CH2), 4.69
(s, 2 H, C≡CCH2), 4.98 (m, 1 H, THP), 7.78 (d, J = 9.1 Hz, 1 H),
8.12 (s, 1 H, NH), 8.16 (s, 1 H), 8.57 (d, J = 9.1 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 14.5, 19.2, 25.0, 25.5, 30.6, 55.6,
61.9, 62.4, 79.2, 97.6, 98.1, 107.0, 119.7, 123.7, 129.6, 135.6,
137.0, 138.2, 139.7, 162.7, 168.7.
HRMS (EI): m/z [M]+ calcd for C21H23NO5S: 401.1297; found:
401.1308.
HRMS (EI): m/z [M]+ calcd for C18H21NO3SSi: 359.1011; found:
359.1016.
Ethyl 5-Acetamido-4-[3-methyl-3-(tetrahydro-2H-pyran-2-
yloxy)but-1-ynyl]benzo[b]thiophene-2-carboxylate (5g)
Yield: 95%; mp 96 °C.
IR: 3300, 2940, 1710, 1690 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.42 (t, J = 7.3 Hz, 3 H, CH3),
1.67 (m, 12 H, C(CH3)2, THP), 2.27 (s, 3 H, CH3CO), 3.56 (m, 1 H,
THP), 4.05 (m, 1 H, THP), 4.42 (q, J = 7.3 Hz, 2 H, CO2CH2), 5.29
(m, 1 H, THP), 7.75 (d, J = 9.1 Hz, 1 H), 8.10 (s, 1 H), 8.55 (d,
J = 9.1 Hz, 1 H), 8.69 (s, 1 H, NH).
13C NMR (75 MHz, CDCl3): d = 14.4, 19.5, 24.4, 25.6, 29.3, 31.1,
32.0, 61.9, 62.2, 70.6, 95.2, 103.8, 107.4, 120.3, 123.2, 129.6,
135.2, 136.9, 138.4, 139.3, 162.7, 169.3.
Ethyl 5-Acetamido-4-(3-hydroxyprop-1-ynyl)benzo[b]thio-
phene-2-carboxylate (5c)
Yield: 44%; mp 190–191 °C.
IR: 3280, 2920, 1700, 1665 cm–1.
1H NMR (300 MHz, CD3OD–CDCl3): d = 1.43 (t, J = 7.3 Hz, 3 H,
CH3), 1.60 (br s, 1 H, OH), 2.27 (s, 3 H, CH3CO), 4.42 (q, J = 7.3
Hz, 2 H, CO2CH2), 4.62 (s, 2 H, CH2O), 7.81 (d, J = 9.1 Hz, 1 H),
8.09 (s, 1 H), 8.18 (d, J = 9.1 Hz, 1 H).
13C NMR (75 MHz, CD3OD–CDCl3): d = 13.1, 22.5, 49.8, 61.2,
71.3, 98.2, 109.9, 122.2, 128.2, 131.2, 134.4, 136.3, 137.4, 139.3,
162.2, 170.0.
HRMS (EI): m/z [M]+ calcd for C23H27NO5S: 429.1610; found:
429.1616.
HRMS (EI): m/z [M]+ calcd for C16H15NO4S: 317.0722; found:
317.0706.
Ethyl 5-Acetamido-4-[4-(tetrahydro-2H-pyran-2-yloxy)but-1-
ynyl]benzo[b]thiophene-2-carboxylate (5h)
Yield: 73%; mp 130 °C.
IR: 3280, 2940, 2230, 1710, 1660 cm–1.
Ethyl 5-Acetamido-4-(3-hydroxy-3-methylbut-1-ynyl)ben-
zo[b]thiophene-2-carboxylate (5d)
Yield: 86%; mp 122–123 °C.
1H NMR (300 MHz, CDCl3): d = 1.42 (t, J = 7.3 Hz, 3 H, CH3),
1.9–1.5 (m, 6 H, THP), 2.26 (s, 3 H, CH3CO), 2.93 (t, J = 7.3 Hz, 2
H, C≡CCH2), 3.55 (m, 1 H, THP), 3.79 (m, 1 H, CH2O), 3.93 (m, 1
H, CH2O), 4.02 (m, 1 H, THP), 4.41 (q, J = 7.3 Hz, 2 H, CO2CH2),
4.73 (m, 1 H, THP), 7.73 (d, J = 9.1 Hz, 1 H), 8.09 (s, 1 H, NH),
8.15 (s, 1 H), 8.52 (d, J = 9.1 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 14.5, 19.7, 21.6, 25.0, 25.5, 30.8,
61.8, 62.8, 65.8, 74.9, 99.2, 100.0, 108.2, 119.6, 122.9, 129.8,
135.2, 137.0, 137.6, 139.7, 162.7, 168.6.
IR: 3240, 2920, 1710, 1670 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.43 (t, J = 7.3 Hz, 3 H, CH3),
1.75 [s, 6 H, C(CH3)2], 2.26 (s, 3 H, CH3CO), 2.67 (br s, 1 H, OH),
4.42 (q, J = 7.3 Hz, 2 H, CO2CH2), 7.73 (d, J = 9.1 Hz, 1 H), 7.97
(s, 1 H, NH), 8.07 (s, 1 H), 8.46 (d, J = 9.1 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 14.4, 24.8, 31.7, 62.0, 65.9, 75.4,
106.3, 107.7, 120.0, 123.3, 129.4, 135.3, 137.2, 137.3, 139.2, 162.7,
168.8.
HRMS (EI): m/z [M]+ calcd for C18H19NO4S: 345.1035; found:
345.1039.
HRMS (EI): m/z [M]+ calcd for C22H25NO5S: 415.1453; found:
415.1454.
Ethyl 5-Acetamido-4-(4-hydroxybut-1-ynyl)benzo[b]thio-
phene-2-carboxylate (5e)
Yield: 90%; mp 131 °C.
IR: 3490, 3390, 3340, 2900, 2230, 1700, 1680 cm–1.
Ethyl 5-Acetamido-4-(hex-1-ynyl)benzo[b]thiophene-2-carbox-
ylate (5i)
Yield: 82%; mp 116–118 °C.
IR: 3380, 2960, 2230, 1710, 1650 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.42 (t, J = 7.3 Hz, 3 H, CH3),
1.92 (s, 1 H, OH), 2.26 (s, 3 H, CH3CO), 2.89 (t, J = 6.4 Hz, 2 H,
C≡CCH2), 3.96 (m, 2 H, CH2OH), 4.42 (q, J = 7.3 Hz, 2 H,
CO2CH2), 7.75 (d, J = 9.1 Hz, 1 H), 8.15 (s, 1 H), 8.21 (s, 1 H, NH),
8.55 (d, J = 9.1 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 14.5, 24.2, 25.0, 61.1, 61.9, 99.5,
108.0, 119.7, 123.0, 129.7, 135.0, 135.3, 137.9, 139.5, 162.8, 168.8.
1H NMR (300 MHz, CDCl3): d = 1.02 (t, J = 7.3 Hz, 3 H, CH3),
1.42 (t, J = 7.3 Hz, 3 H, CH3), 1.59 (m, 2 H, CH2), 1.73 (m, 2 H,
CH2), 2.26 (s, 3 H, CH3CO), 2.64 (t, J = 7.3 Hz, 2 H, C≡CCH2), 4.41
(q, J = 7.3 Hz, 2 H, CO2CH2), 7.72 (d, J = 9.1 Hz, 1 H), 7.99 (s, 1
H, NH), 8.14 (s, 1 H), 8.55 (d, J = 9.1 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 13.6, 14.3, 19.6, 22.2, 24.9, 30.8,
61.7, 73.9, 102.9, 108.4, 119.4, 122.5, 129.8, 134.9, 136.9, 137.1,
139.6, 162.6, 168.2.
HRMS (EI): m/z [M]+ calcd for C17H17NO4S: 331.0878; found:
331.0879.
HRMS (EI): m/z [M]+ calcd for C19H21NO3S: 343.1242; found:
343.1242.
Ethyl 5-Acetamido-4-[3-(tetrahydro-2H-pyran-2-yloxy)prop-1-
ynyl]benzo[b]thiophene-2-carboxylate (5f)
Yield: 81%; mp 130 °C.
IR: 3300, 2930, 2220, 1710, 1670 cm–1.
Ethyl 5-Acetamido-4-(phenylethynyl)benzo[b]thiophene-2-car-
boxylate (5a); Typical Procedure by Acetylation of 4a
To a stirred soln of 4a (404 mg, 1.24 mmol) and Et3N (0.19 mL,
1.37 mmol) in CH2Cl2 (10 mL) at 0 °C was added AcCl (106 mg,
1.37 mmol). The mixture was allowed to warm to r.t., stirred for 2.5
Synthesis 2009, No. 5, 767–774 © Thieme Stuttgart · New York