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H.-G. Häcker et al.
PAPER
(m, 2 H, H-5¢/7¢), 3.94 (s, 2 H, CH2), 4.10 (q, J = 7.1 Hz, 2 H, CH2),
6.96 (br s, 2 H, NH2).
7.69 (ddd, J = 7.9, 7.1, 1.6 Hz, 1 H, H-7¢), 7.85 (br s, 2 H, NH2),
8.13 (dd, J = 8.2, 1.6 Hz, 1 H, H-5¢).
13C NMR (125 MHz, DMSO-d6): d = 14.25, 27.34, 28.81, 29.11,
32.81, 60.90, 109.55, 134.63, 136.02, 157.39, 163.09, 169.38,
171.42.
13C NMR (125 MHz, DMSO-d6): d = 14.26, 32.79, 60.86, 112.70,
123.92, 124.55, 126.09, 133.41, 150.04, 161.34, 165.58, 169.54.
Anal. Calcd for C12H13N3O2S: C, 54.74; H, 4.98; N, 15.96. Found:
C, 54.45; H, 5.10; N, 15.54.
Anal. Calcd for C13H15N3O2S2: C, 50.46; H, 4.89; N, 13.58. Found:
C, 50.20; H, 4.94; N, 13.44.
Ethyl [(4-Amino-6,7-dimethoxyquinazolin-2-yl)sulfanyl]ace-
tate (3h)
White needles; yield: 659 mg (68%); mp 178–181 °C (EtOH);
Rf = 0.27 (toluene–EtOAc, 4:1).
Ethyl [(4-Amino-5,6,7,8-tetrahydrobenzothieno[2,3-d]pyrimi-
din-2-yl)sulfanyl]acetate (3d)
White needles; yield: 468 mg (48%); mp 139–140 °C (EtOH) (Lit.19
138–141 °C); Rf = 0.22 (toluene–EtOAc, 4:1).
IR (KBr): 3108, 2888, 1725, 1661 cm–1.
IR (KBr): 3511, 3296, 3130, 2930, 1740, 1632 cm–1.
1H NMR (500 MHz, DMSO-d6): d = 1.20 (t, J = 7.0 Hz, 3 H, CH3),
3.01 (s, 3 H, CH3), 3.86 (s, 3 H, CH3), 3.97 (s, 2 H, CH2), 4.12 (q,
J = 7.0 Hz, 2 H, CH2), 6.87 (s, 1 H, H-5¢/8¢), 7.51 (br s, 2 H, NH2),
7.52 (s, 1 H, H-5¢/8¢).
13C NMR (125 MHz, DMSO-d6): d = 14.25, 32.65, 55.76, 56.09,
60.81, 103.34, 105.87, 106.01, 147.13, 147.56, 154.49, 160.32,
163.25, 169.66.
1H NMR (500 MHz, DMSO-d6): d = 1.18 (t, J = 7.1 Hz, 3 H, CH3),
1.75–1.79 (m, 4 H, H-6¢/7¢), 2.69–2.70 (m, 2 H, H-5¢/8¢), 2.83–2.84
(m, 2 H, H-5¢/8¢), 3.93 (s, 2 H, CH2), 4.10 (q, J = 7.1 Hz, 2 H, CH2),
6.86 (br s, 2 H, NH2).
13C NMR (125 MHz, DMSO-d6): d = 14.26, 22.06, 22.37, 24.83,
32.76, 60.88, 112.45, 126.96, 129.48, 157.76, 163.09, 166.09,
169.37.
Anal. Calcd for C14H17N3O4S: C, 52.00; H, 5.30; N, 12.99. Found:
C, 52.14; H, 5.30; N, 13.00.
Anal. Calcd for C14H17N3O2S2: C, 51.99; H, 5.30; N, 12.99. Found:
C, 51.69; H, 5.57; N, 12.59.
N-[3-(o-Cyanoaryl)-4-oxo-1,3-thiazolidin-2-ylidene]benz-
amides 4; General Procedure
Ethyl [(4-Amino-5,8-dihydro-6H-pyrano[4¢,3¢:4,5]thieno[2,3-
d]pyrimidin-2-yl)sulfanyl]acetate (3e)
Colorless blocks; yield: 726 mg (74%); mp 192–193 °C (EtOH);
Rf = 0.40 (toluene–EtOAc, 4:1).
The appropriate N-benzoyl-N¢-(o-cyanoaryl)thiourea 2 (1.00 mmol)
was dissolved in a mixture of EtOH (3.0 mL) and 1 M NaOH
(1.5 mL). The soln was heated to 50 °C and ethyl bromoacetate
(200 mg, 133 mL, 1.20 mmol) was added within 1 min. If turbidity
was observed, a few drops of 1 M NaOH were added to prevent pre-
cipitation. After heating at 50 °C for 1 h, the mixture was cooled to
r.t. and H2O (5 mL) was added, and the precipitate was removed by
suction filtration, washed with H2O (50 mL), and dried in vacuo.
Pure material was obtained by recrystallization from EtOH.
IR (KBr): 3489, 3294, 3161, 2968, 1727, 1631 cm–1.
1H NMR (500 MHz, DMSO-d6): d = 1.18 (t, J = 7.1 Hz, 3 H, CH3),
2.95 (tt, J = 5.5, 1.9 Hz, 2 H, H-5¢), 3.91 (t, J = 5.5 Hz, 2 H, H-6¢),
3.95 (s, 2 H, CH2), 4.10 (q, J = 7.1 Hz, 2 H, CH2), 4.71 (t,
J = 1.9 Hz, 2 H, H-8¢), 6.97 (br s, 2 H, NH2).
13C NMR (125 MHz, DMSO-d6): d = 14.25, 26.02, 32.80, 60.90,
63.94, 64.58, 111.89, 124.86, 127.23, 157.81, 163.60, 166.60,
169.32.
N-[3-(3-Cyano-2-thienyl)-4-oxo-1,3-thiazolidin-2-ylidene]-
benzamide (4a)
White needles; yield: 245 mg (71%); mp 191–192 °C (EtOH);
Anal. Calcd for C13H15N3O3S2: C, 47.98; H, 4.65; N, 12.91. Found:
C, 47.89; H, 4.64; N, 12.86.
Rf = 0.40 (PE–EtOAc, 2:1).
Material for X-ray crystallography was recrystallized from EtOAc.
IR (KBr): 3111, 2970, 2234, 1755, 1648 cm–1.
1H NMR (500 MHz, DMSO-d6): d = 4.29 (s, 2 H, H-5¢), 7.46–7.51
(m, 2 H, H-3/5), 7.59–7.63 (m, 2 H, H-4/4¢¢/5¢¢), 7.93–7.96 (m, 2 H,
H-2/6), 7.99 (d, J = 5.7 Hz, 1 H, H-4¢¢/5¢¢).
13C NMR (125 MHz, DMSO-d6): d = 33.58, 109.71, 113.25,
127.15, 128.86, 129.52, 129.77, 133.71, 134.61, 143.04, 171.48,
172.66, 176.12.
Ethyl [(4-Amino-7-benzyl-5,6,7,8-tetrahydropyrido-
[4¢,3¢:4,5]thieno[2,3-d]pyrimidin-2-yl)sulfanyl]acetate (3f)
Yellow needles; yield: 611 mg (49%); mp 143–144 °C (EtOH);
Rf = 0.24 (toluene–EtOAc, 4:1).
IR (KBr): 3501, 3283, 3107, 2911, 1741, 1634 cm–1.
1H NMR (500 MHz, DMSO-d6): d = 1.19 (t, J = 7.1 Hz, 3 H, CH3),
2.77 (t, J = 5.7 Hz, 2 H, H-5¢/6¢), 2.94 (t, J = 5.7 Hz, 2 H, H-5¢/6¢),
3.60 (s, 2 H, H-8¢), 3.70 (s, 2 H, CH2), 3.96 (s, 2 H, CH2), 4.11 (q,
J = 7.1 Hz, 2 H, CH2), 6.94 (br s, 2 H, NH2), 7.26–7.30 (m, 1 H, H-
4¢¢), 7.33–7.38 (m, 4 H, H-2¢¢/3¢¢/5¢¢/6¢¢).
Anal. Calcd for C15H9N3O2S2·H2O: C, 52.16; H, 3.21; N, 12.17.
Found: C, 52.25; H, 3.25; N, 12.18.
13C NMR (125 MHz, DMSO-d6): d = 14.25, 25.65, 32.78, 48.97,
51.39, 60.75, 60.89, 111.95, 125.61, 127.11, 127.23, 128.40,
128.94, 138.29, 157.80, 163.44, 166.43, 169.33.
N-[3-(3-Cyano-4,5-dimethyl-2-thienyl)-4-oxo-1,3-thiazolidin-2-
ylidene]benzamide (4b)
Pale yellow plates; yield: 223 mg (63%); mp 218–221 °C (EtOH);
Rf = 0.62 (toluene–EtOAc, 4:1).
IR (KBr): 2230, 1751, 1649 cm–1.
Anal. Calcd for C20H22N4O2S2: C, 57.95; H, 5.35; N, 13.52. Found:
C, 57.70; H, 5.56; N, 13.35.
1H NMR (500 MHz, DMSO-d6): d = 2.26 (s, 3 H, CH3), 2.45 (s,
3 H, CH3), 4.27 (s, 2 H, H-5¢), 7.48–7.52 (m, 2 H, H-3/5), 7.60–7.62
(m, 1 H, H-4), 7.96–7.98 (m, 2 H, H-2/6).
13C NMR (125 MHz, DMSO-d6): d = 12.56, 13.24, 33.44, 111.67,
113.24, 128.89, 129.57, 132.05, 133.68, 134.60, 136.16, 138.21,
171.49, 172.41, 176.25.
Ethyl [(4-Aminoquinazolin-2-yl)sulfanyl]acetate (3g)
White needles; yield: 438 mg (55%); mp 153–154 °C (EtOH) (Lit.19
151–152 °C); Rf = 0.88 (EtOAc).
IR (KBr): 3406, 3173, 2973, 1735, 1646 cm–1.
1H NMR (500 MHz, DMSO-d6): d = 1.19 (t, J = 7.0 Hz, 3 H, CH3),
3.98 (s, 2 H, CH2), 4.11 (q, J = 7.0 Hz, 2 H, CH2), 7.36 (ddd,
J = 8.2, 6.9, 1.3 Hz, 1 H, H-6¢), 7.45 (dd, J = 8.2, 1.3 Hz, 1 H, H-8¢),
Anal. Calcd for C17H13N3O2S2: C, 57.45; H, 3.69; N, 11.82. Found:
C, 57.02; H, 3.92; N, 11.53.
Synthesis 2009, No. 7, 1195–1203 © Thieme Stuttgart · New York