P. Langer, A. Bodtke / Tetrahedron Letters 44 (2003) 5965–5967
5967
6. Thom, A.; Zinner, G. Arch. Pharm. (Weinheim Ger.) 1994,
327, 469.
(C-6a), 142.9 (C=N), 162.1 (d, JC,F=245 Hz, C-4%), 166.8
(C=S). MS (EI, 70 eV): m/z [%]=296 ([M+H]+, 22), 295
(M+, 100), 294 ([M−H]+, 83), 262 ([M−SH]+, 3), 108 (17),
107 (16). UV (CH3CN, nm): umax (log m)=220 (4.18), 259
(4.60), 283 (4.52), 323 (4.09), 340 (4.09), 354 (3.99). Anal.
calcd for C16H10FN3S (295.34): C, 65.07; H, 3.41; N,
14.23. Found: C, 65.19, H, 3.54, N, 14.14.
7. For related heterocycles prepared by other methods, see:
(a) Chern, J.-W.; Tao, P.-L.; Wang, K.-C.; Gutcait, A.;
Liu, S.-W.; Yen, M.-H.; Chien, S.-L.; Rong, J.-K. J. Med.
Chem. 1998, 41, 3128; (b) Arnold, W.; Buettelmann, B.;
Heitz, M.-P.; Wyler, R. Heterocycles 1996, 43, 2607; (c)
Chern, J.-W.; Tao, P.-L.; Yen, M.-H.; Lu, G.-Y.; Shiau,
C.-Y.; Lai, Y.-J.; Chien, S.-L.; Chan, C.-H. J. Med. Chem.
1993, 36, 2196; (d) Molina, P.; Alajarin, M.; Vidal, A.
Tetrahedron Lett. 1988, 3849; (e) Nishio, T.; Fujisawa, M.;
Omote, Y. J. Chem. Soc., Perkin Trans. 1 1987, 2523; (f)
Leistner, S.; Wagner, G.; Strohscheidt, T. Pharmazie 1980,
35, 293.
9. Typical procedure 2: 5-Oxo-5,6-dihydro-imidazo[1,2-
c]quinazolines (3k–n): To a CH2Cl2 suspension (40 mL) of
isocyanatobenzonitrile (325 mg, 2.4 mmol) and 1-(a-
aminoacetyl)-4-toluene hydrochloride (520 mg, 2.4 mmol)
was added dropwise a CH2Cl2 solution (10 mL) of NEt3
(246 mg). The mixture was stirred for 10 min at 20°C and
for 40 min under reflux. Upon cooling to ambient a
colorless solid formed (intermediate A) which was filtered
off and dried by exposure to air (630 mg, 88%). IR (KBr):
w˜=3322 (s, NH), 2226 (w, CN), 1682 (s, CꢀO), 1649 (s,
CONH), 1607 (s), 1571 (s, CONH), 1537 (s), 1476 (w),
1450 (m), 1414 (w), 1358 (w), 1298 (m), 1232 (s), 1184 (w)
8. Typical procedure for the synthesis of 5-thioxo-5,6-dihydro-
imidazo[1,2-c]quinazolines (3a–j): To a CH2Cl2 suspension
(40 mL) of isothiocyanatobenzonitrile (1.00 g, 6.4 mmol)
and 4-(a-aminoacetyl)-1-fluorobenzene hydrochloride (1.21
g, 6.4 mmol) was added an aqueous solution (12 mL) of
sodium carbonate (1.38 g) with stirring. The mixture was
stirred for 10 min at 20°C and for 10 min under reflux.
After cooling to room temperature a colorless precipitate
formed (intermediate B) which was filtered off. The
organic and the aqueous layer of the filtrate were sepa-
rated and the aqueous layer was extracted with CH2Cl2
(2×20 mL). The combined organic layers were concen-
trated at reduced pressure. The residue and the precipitate
were suspended in EtOH (200 mL) and the mixture was
refluxed for 12 h. The product 3f, which crystallized upon
cooling, was filtered off and dried in vacuo. The filtrate
was concentrated at reduced pressure to give an additional
amount of 3f (combined yield: 1.48 g, 78%). Data of
2-(p-fluorophenyl)-5-thioxo-5,6-dihydro-imidazo[1,2-c]-
quinazoline (3f): Colorless prisms (EtOH), mp 327–332°C
(decomp.). IR (KBr, cm−1): w˜=3179 (m), 3141 (m), 3113
(m), 3092, 3033 (m, Ar-H, CꢀCH), 2975 (m), 1634 (s), 1608
(m), 1566 (w), 1540 (s), 1494 (s), 1477 (s), 1467 (w), 1416
(s), 1359 (s), 1316 (s), 1303 (m), 1295 (m), 1283 (w), 1230
(m), 1219 (m), 1208 (w), 1193 (s), 1156 (s), 842 (s), 747 (s).
1H NMR (DMSO-d6, 300 MHz): l=7.49–7.69 (m, 5H,
Ar-H), 8.06–8.31 (m, 3H, Ar-H), 8.73 (s, 1H, 3-H), 13.82
(bs, 1H, NH). 13C NMR (DMSO-d6, 75 MHz): l=112.6
(Ar-CH, C-3), 113.5 (10a), 115.7 (d, JC,F=21 Hz, C-3%,
C-5%), 116.4 (Ar-CH, C-10), 123.1 (Ar-CH, C-9), 125.5
(Ar-CH, C-7), 127.8 (2 d, JC,F=8 Hz, C-2%, C-6%), 129.0 (d,
cm−1 1H NMR (DMSO-d6, 300 MHz): l=2.40 (s, 3H,
.
CH3), 4.71 (d, J=5.1 Hz, 2H, CH2), 7.09–8.06 (m, 9H,
Ar-H, NH), 8.98 (s, 1H, NH). An iPrOH (100 mL)
suspension of A (360 mg, 1.2 mmol) and of ammonium
hydroxide (20 mL) was refluxed for 20 h. The solution was
cooled to ambient and concentrated in vacuo to give a
colorless precipitate which was filtered off and dried in
vacuo. The solid was recrystallized from iPrOH to give 3m
(255 mg, 78%) as colorless needles, mp 302–303°C. IR
(KBr, cm−1): w˜=3213 (w, NH), 3155 (m, NH), 3077, 3064,
3053, 3015 (m, Ar-H, CꢀCH), 2943, 2923, 2894 (m, CH3),
1710 (s, CꢀO), 1599 (s), 1556 (s), 1497 (m), 1483 (m), 1416
(s), 1371 (m), 1330 (w), 1296 (m), 1253 (w), 1147 (w), 830
1
(w), 822 (m), 747 (s), 737 (m). H NMR (DMSO-d6, 300
MHz): l=2.35 (s, 3H, CH3), 7.25–8.22 (m, 8H, Ar-H),
8.34 (s, 1H, 3-H), 12.00 (s, 1H, NH). 13C NMR (DMSO-
d6, 75 MHz): l=20.8 (CH3), 108.9 (C-3), 112.0 (10a),
115.8 (Ar-CH, C-10), 122.8 (Ar-CH, C-9), 123.3 (Ar-CH,
C-7), 125.4 (Ar-CH, C-3%, C-5%), 129.2 (Ar-CH, C-2%, C-6%),
130.1 (C-1%), 130.4 (Ar-CH, C-8), 135.2 (C-2), 137.0 (C-4%),
143.1 (C-6a), 143.3 (CꢀN), 144.8 (CꢀO). MS (EI, 70 eV):
m/z [%]=276 ([M+H]+, 19), 275 (M+, 100), 247 ([M−CO]+,
4), 130 (11). UV (CH3CN, nm): umax (log m)=242 (4.62),
249 (4.60), 273 (4.30), 312 (4.11), 324 (4.19). Anal. calcd
for C17H13N3O (275.31): C, 74.17; H, 4.76; N, 15.26.
Found: C, 74.14, H, 4.78, N, 15.14.
J
C,F=3 Hz, C-1%), 131.0 (Ar-CH, C-8), 134.5 (C-2), 139.9