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A. Witt, J. Bergman / Tetrahedron 56 (2000) 7245–7253
over night. The mixture was quenched with HOAc (0.2 mL)
and concentrated under reduced pressure to afford a yellow
oil, which was purified by chromatography on silica gel
column (4:1, ethyl acetate in hexane as the eluent) to give
compound 17a (260 mg, 41%) as a colourless oil; IR (neat)
3368, 2979, 1738, 1668, 1599, 1474, 1201, 1013, 775,
698 cmϪ1; dH (CDCl3) 1.24 (6H, t, J7.1 Hz), 2.04 (3H,
s), 2.78–2.90 (4H, m), 3.60 (3H, s), 4.16–4.28 (4H, m),
6.93 (1H, s), 7.44 (1H, dd, J7.8, 6.9 Hz), 7.59 (1H, d,
J7.8 Hz), 7.69 (1H, ddd, J8.2, 6.9, 1.5 Hz), 8.22 (1H,
dd, J8.2, 1.2 Hz); dC (CDCl3) 13.9 (q), 23.0 (q), 30.0 (t),
30.2 (t), 30.3 (q), 62.7 (t), 65.6 (s), 120.1 (s), 126.4 (d),
126.6 (d), 126.8 (d), 134.0 (d), 146.9 (s), 155.6 (s), 162.3
(s), 167.7 (s), 169.4 (s); Anal. Calcd for C20H25N3O6: C,
59.54; H, 6.25; N, 10.42. Found: C, 59.46; H, 6.34; N, 10.32.
J8.0 Hz), 7.75 (1H, ddd, J7.9, 7.0, 1.2 Hz), 8.06 (1H,
dd, J7.9, 1.3 Hz); dC 11.9 (q), 32.0 (t), 46.1 (t), 49.8 (t),
120.8 (s), 125.7 (d), 125.9 (d), 126.7 (d), 134.9 (d), 149.0
(s), 156.9 (s), 161.8 (s).
2-(2-Diethylaminoethyl)-3-methyl-3H-quinazolin-4-one
(17c). Diethylamine (distilled from CaH2, 149 mg, 2 mmol)
and HOAc (0.1 mmol) were added to a mixture of the vinyl-
quinazolinone 14 (190 mg, 1 mmol) in MeOH (10 mL). The
solution was heated to reflux over night. After evaporation,
the residue was dissolved in ice-water (ϳ20 mL). The
aqueous solution was made basic with 2 M NaOH and
extracted with ethyl acetate (25 mL×2). The combined
extracts were dried (MgSO4) and concentrated under
reduced pressure to give compound 17c (225 mg, 85%) as
a yellow oil; IR (neat) 2970, 1674, 1599, 1474, 1421, 1338,
1011, 774, 697 cmϪ1; dH (CDCl3) 1.05 (6H, t, J7.1 Hz),
2.60 (4H, q, J7.1 Hz), 2.96 (4H, s), 3.62 (3H, s), 7.39 (1H,
dd, J7.9, 6.9 Hz), 7.59 (1H, d, J7.9 Hz), 7.67 (1H, ddd,
J8.0, 6.9, 1.3 Hz), 8.21 (1H, dd, J8.0, 0.8 Hz); dC
(CDCl3) 12.3 (q), 31.0 (q), 34.0 (t), 47.6 (t), 50.6 (t),
120.6 (s), 126.7 (d), 127.1 (d), 127.2 (d), 134.4 (d), 147.6
(s), 156.5 (s), 162.9 (s); Anal. Calcd for C15H21N3O:
C, 69.47; H, 8.16; N, 16.20. Found: C, 69.56; H, 8.04; N,
16.11.
2-[2-(1H-Indol-3-yl)-ethyl]-3H-quinazolin-4-one (16b).
A mixture of the vinylquinazolinone 11a (1.02 g,
5.9 mmol) and indole (0.79 g, 6.7 mmol) in HOAc (6 mL)
was heated to reflux for 4 h. A white precipitate was
collected and washed with EtOH to give compound 16b
(1.62 g, 95%); mp 302–303ЊC; IR (KBr) 3176, 3043,
2918, 1682, 1613, 1469, 1335, 1231, 1072, 770,
732 cmϪ1; dH 2.95–3.01 (2H, m), 3.15–3.22 (2H, m),
6.96 (1H, dd, J7.9, 7.0 Hz), 7.06 (1H, dd, J8.0,
7.0 Hz), 7.15 (1H, d, J2.0 Hz), 7.33 (1H, d, J8.0 Hz),
7.44 (1H, ddd, J7.9, 7.0, 1.0 Hz), 7.60–7.65 (2H, m), 7.76
(1H, ddd, J8.1, 7.0, 1.5 Hz), 8.09 (1H, dd, J8.1, 1.1 Hz),
10.79 (1H, s), 12.28 (1H, s); dC 22.7 (t), 35.7 (t), 111.4 (d),
113.3 (s), 118.2 (d), 118.5 (d), 120.8 (s), 121.0 (d), 122.4
(d), 125.7 (d), 125.9 (d), 126.8 (d), 127.0 (s), 134.3 (d),
136.2 (s), 148.9 (s), 157.3 (s), 161.9 (s); MS (EI) m/z (rel.
intensity) 290 (Mϩϩ1, 3%), 289 (Mϩ, 15), 130 (100), 44
(47), 40 (33); Anal. Calcd for C18H15N3O: C, 74.72; H, 5.22;
N, 14.52. Found: C, 74.64; H, 5.31; N, 14.44.
2-(2-Piperidin-1-yl-ethyl)-3H-quinazolin-4-one
(16d).
Similarly prepared as compound 16c using the vinylquina-
zolinone 11a and piperidine. Yield; 84%. Compound 16d
was recrystallised from ethyl acetate to yield an analytically
pure substance. White solid; mp 148–149ЊC (Lit.,23 mp
148ЊC); IR (KBr) 3168, 3100, 2933, 2745, 1680, 1620,
1609, 1468, 1248, 894, 769 cmϪ1; dH 1.31–1.40 (2H, m),
1.40–1.53 (4H, m), 2.35–2.45 (4H, m), 2.66–2.81 (4H, m),
7.43 (1H, dd, J8.0, 7.2 Hz), 7.57 (1H, d, J8.0 Hz), 7.75
(1H, ddd, J8.0, 7.2, 1.0 Hz), 8.06 (1H, dd, J8.0, 0.6 Hz),
12.24 (1H, s); dC 24.0 (t), 25.6 (t), 31.8 (t), 53.6 (t), 55.8 (t),
120.8 (s), 125.6 (d), 125.9 (d), 126.7 (d), 134.2 (d), 148.9
(s), 156.7 (s), 161.7 (s).
2-[2-(1H-Indol-3-yl)-ethyl]-3-methyl-3H-quinazolin-4-one
(17b). Similarly prepared as compound 16b using the vinyl-
quinazolinone 14. Yield; 75%. White solid; mp 185–186ЊC;
IR (KBr) 3262, 1665, 1588, 1470, 1340, 1232, 1008,
742 cmϪ1; dH 3.20 (4H, s), 3.52 (3H, s), 6.97 (1H, dd,
J7.9, 7.1 Hz), 7.07 (1H, dd, J 7.9, 7.1 Hz), 7.24 (1H,
d, J2.2 Hz), 7.35 (1H, d, J7.9 Hz), 7.47 (1H, ddd,
J7.9, 7.0, 1.0 Hz), 7.58 (1H, d, J7.9 Hz), 7.66 (1H, d,
J7.9 Hz), 7.78 (1H, ddd, J8.1, 7.0, 1.4 Hz), 8.11 (1H, dd,
J8.1, 1.0 Hz), 10.82 (1H, s); dC 21.8 (t), 29.9 (q), 35.3 (t),
111.4 (d), 113.5 (s), 118.3 (d), 118.3 (d), 119.8 (s), 120.9
(d), 122.6 (d), 126.2 (d), 126.2 (d), 126.8 (d), 127.1 (s),
134.1 (d), 136.3 (s), 147.0 (s), 157.5 (s), 161.4 (s); Anal.
Calcd for C19H17N3O: C, 75.23; H, 5.65; N, 13.85. Found:
C, 75.19; H, 5.77; N, 13.81.
3-Methyl-2-(2-piperidin-1-yl-ethyl)-3H-quinazolin-4-one
(17d). Similarly prepared as compound 17c using the vinyl-
quinazolinone 14 and piperidine (distilled from CaH2).
Yield; 100%. Light yellow oil; IR (neat) 2934, 2854,
1674, 1599, 1474, 1422, 1338, 1118, 1012, 773, 698
cmϪ1; dH (CDCl3) 1.40–1.53 (2H, m), 1.58–1.68 (4H, m),
2.47–2.63 (4H, m), 2.85–2.98 (2H, m), 2.98–3.10 (2H, m),
3.63 (3H, s), 7.41 (1H, dd, J8.1, 6.9 Hz), 7.60 (1H, d,
J8.1 Hz), 7.69 (1H, dd, J8.1, 6.9 Hz), 8.23 (1H, dd,
J8.1, 1.4 Hz); dC (CDCl3) 24.3 (t), 25.9 (t), 30.7 (q),
33.0 (t), 54.7 (t), 56.1 (t), 120.4 (s), 126.6 (d), 126.9 (d),
127.0 (d), 134.2 (d), 147.3 (s), 155.9 (s), 162.6 (s); Anal.
Calcd for C16H21N3O: C, 70.82; H, 7.80; N, 15.48. Found:
C, 70.67; H, 7.89; N, 15.32.
2-(2-Diethylaminoethyl)-3H-quinazolin-4-one (16c). Di-
ethylamine (149 mg, 2 mmol) and HOAc (0.1 mmol) were
added to a mixture of the vinylquinazolinone 11a (175 mg,
1 mmol) in MeOH (10 mL). The solution was heated to
reflux over night. After evaporation, the residue was recrys-
tallised from hexane to give compound 16c (123 mg, 49%)
as white crystals; mp 115–117ЊC (Lit.,23 mp 122ЊC); IR
(KBr) 3172, 3034, 2974, 2799, 1682, 1618, 1466, 1320,
1206, 1067, 904, 776 cmϪ1; dH 0.93 (6H, t, J7.1 Hz),
2.48 (4H, q, J7.1 Hz), 2.70 (2H, t, J6.9 Hz), 2.83 (2H,
t, J6.9 Hz), 7.43 (1H, dd, J8.0, 7.0 Hz), 7.57 (1H, d,
2-(2-Azidoethyl)-3H-quinazolin-4-one (16e). Sodium
azide (0.34 g, 5.2 mmol) dissolved in water (5 mL) was
added to a stirred solution of the vinylquinazolinone 11a
(0.58 g, 3.4 mmol) in THF (25 mL). After 1 h at room
temperature the solution was heated to 60ЊC over night.
The solution was acidified with 10% HCl and then diluted
with water (50 mL). The aqueous phase was extracted with
ethyl acetate (2×50 mL). The combined extracts were dried