PAPER
Lithiation and Side-Chain Substitution of 2-Alkyl-4-(methylthio)quinazolines
2959
2-[(1R*,2R*)-2-Hydroxy-2-(4-methoxyphenyl)-1-methylethyl]-
4-methoxyquinazoline (32b)
Mp 116 °C.
2-(2-Hydroxy-1-ethyl-2,2-diphenylethyl)-4-methoxyquinazo-
line (35)
Mp 139–140 °C.
1H NMR (CDCl3): d = 8.03 (dd, J = 1, 8 Hz, 1 H, H-8), 7.79 (br d,
J = 8 Hz, 1 H, H-5), 7.71 (app. dt, J = 1, 8 Hz, 1 H, H-7), 7.42 (app.
dt, J = 1, 8 Hz, 1 H, H-6), 7.28 (d, J = 8.5 Hz, 2 H, H-2, H-6 of Ar),
6.76 (d, J = 8.5 Hz, 2 H, H-3, H-5 of Ar), 5.17 (br s, exch., 1 H, OH),
4.89 (d, J = 7 Hz, 1 H, CHOH), 4.08 (s, 3 H, OCH3), 3.69 (s, 3 H,
OCH3), 3.34 (app. quin, J = 7 Hz, 1 H, CHCH3), 1.24 (d, J = 7 Hz,
3 H, CH3).
1H NMR (CDCl3): d = 7.91 (dd, J = 1, 8 Hz, 1 H, H-8), 7.72 (br d,
J = 8 Hz, 1 H, H-5), 7.65–7.54 (m, 5 H, H-7, H-2, H-6 of 2 × Ph),
7.32 (app. dt, J = 1, 8 Hz, 1 H, H-6), 7.23 (app. t, J = 7.5 Hz, 2 H,
H-3, H-5 of Ph), 7.09–7.05 (m, 2 H, OH, H-4 of Ph), 6.96 (app. t,
J = 7.5 Hz, 2 H, H-3, H-5 of Ph), 6.81 (t, J = 7.5 Hz, 1 H, H-4 of
Ph), 4.02 (br s, 4 H, CH, OCH3), 1.90 (m, 1 H, CHH), 1.69 (m, 1 H,
CHH), 0.68 (d, J = 7.5 Hz, 3 H, CH3).
13C NMR (CDCl3): d = 168.8 (s, C-4), 167.5 (s, C-2), 159.2 (s, C-4
of Ar), 150.9 (s, C-8a), 135.9 (s, C-1 of Ar), 134.1 (d, C-7), 128.3
(d, C-8), 127.3 (d, C-2, C-6 of Ar), 126.9 (d, C-6), 123.9 (d, C-5),
115.4 (s, C-4a), 114.0 (d, C-3, C-5 of Ar), 77.6 (d, CHOH), 55.6 (q,
OCH3), 54.7 (q, OCH3), 49.6 (d, CHCH3), 18.0 (q, CH3).
EI–MS: m/z (%) = 324 (1) [M+], 309 (11), 188 (100), 187 (88), 173
(80), 160 (26), 155 (20), 137 (52), 136 (65), 135 (86), 119 (41), 102
(33), 92 (51), 77 (78), 68 (66), 51 (34), 39 (38).
13C NMR (CDCl3): d = 168.0 (s, C-4), 166.7 (s, C-2), 150.7 (s, C-
8a), 149.0, 146.8 (2 × s, C-1 of 2 × Ph), 134.1 (d, C-7), 128.5, 128.1
(2 × d, C-3, C-5 of 2 × Ph), 127.5 (d, C-4 of 2 × Ph), 126.9 (d, C-8),
126.5 (d, C-6), 126.3, 125.8 (2 × d, C-2, C-6 of 2 × Ph), 123.8 (d, C-
5), 115.0 (s, C-4a), 80.3 (s, COH), 57.1 (d, CH), 54.8 (q, OCH3),
24.2 (t, CH2), 12.8 (q, CH3).
EI–MS: m/z (%) = 384 (1) [M+], 369 (11), 229 (90), 187 (63), 174
(28), 158 (30), 158 (31), 105 (100), 77 (94), 68 (23), 51 (63), 41
(65).
CI–MS: m/z (%) = 325 (30) [MH+], 307 (11), 189 (100), 175 (8),
154 (58), 137 (57).
CI–MS: m/z (%) = 385 (21) [MH+], 287 (7), 204 (29), 203 (100),
200 (72), 183 (73), 174 (12), 105 (9).
HRMS: m/z [MH+] calcd for C25H25N2O2: 385.1911; found:
HRMS: m/z [MH+] calcd for C19H21N2O3: 325.1547; found:
325.1550.
385.1911.
2-(2-Hydroxy-1-methyl-2,2-diphenylethyl)-4-methoxyquinazo-
line (33)
2-Butyl-2-ethyl-4-(methylthio)-1,2-dihydroquinazoline (36)
Mp 91–93 °C.
Oil.
1H NMR (CDCl3): d = 8.04 (dd, J = 1, 8 Hz, 1 H, H-8), 7.82 (br d,
J = 8 Hz, 1 H, H-5), 7.75 (app. dt, J = 1, 8 Hz, 1 H, H-7), 7.68 (d,
J = 7.5 Hz, 4 H, H-2, H-6 of 2 × Ph), 7.45 (app. dt, J = 1, 8 Hz, 1 H,
H-6), 7.36 (app. t, J = 7.5 Hz, 2 H, H-3, H-5 of Ph), 7.28 (s, exch.,
1 H, NH), 7.22 (t, J = 7.5 Hz, 1 H, H-4 of Ph), 7.13 (t, J = 7.5 Hz, 2
H, H-3, H-5 of Ph), 6.99 (t, J = 7.5 Hz, 1 H, H-4 of Ph), 4.60 (q, J =
7 Hz, 1 H, CH), 4.15 (s, 3 H, OCH3), 1.37 (d, J = 7 Hz, 3 H, CH3).
13C NMR (CDCl3): d = 169.6 (s, C-4), 167.1 (s, C-2), 150.9 (s, C-
8a), 149.2, 146.6 (2 × s, C-1 of 2 × Ph), 134.2 (d, C-7), 128.5, 128.2
(2 × d, C-3, C-5 of 2 × Ph), 127.4 (d, C-8), 126.6 (d, C-4 of 2 × Ph),
126.5 (d, C-6), 126.4, 125.6 (2 × d, C-2, C-6 of 2 × Ph), 123.9 (d, C-
5), 115.0 (s, C-4a), 79.9 (s, COH), 54.8 (q, OCH3), 49.8 (d, CH),
16.8 (q, CH3).
1H NMR (CDCl3): d = 7.28 (dd, J = 1, 8 Hz, 1 H, H-5), 7.03 (app.
dt, J = 1, 8 Hz, 1 H, H-7), 6.49 (app. dt, J = 1, 8 Hz, 1 H, H-6), 6.34
(dd, J = 1, 8 Hz, 1 H, H-8), 3.66 (br s, exch., 1 H, NH), 2.30 (s, 3 H,
SCH3), 1.70–1.48 (m, 4 H, 2 × CH2), 1.35–1.18 (m, 4 H, 2 × CH2),
0.82 (t, J = 7.5 Hz, 3 H, CH3), 0.80 (t, J = 7 Hz, 3 H, CH3).
13C NMR (CDCl3): d = 159.6 (s, C-4), 144.4 (s, C-8a), 132.9 (d, C-
7), 125.4 (d, C-5), 117.0 (d, C-6), 116.3 (s, C-4a), 113.7 (d, C-8),
76.0 (s, C-2), 41.1 (t, CH2), 34.3 (t, CH2), 26.3 (t, CH2), 23.8 (t,
CH2), 14.6 (q, CH3), 12.5 (q, CH3), 8.5 (q, CH3).
EI–MS: m/z (%) = 262 (3) [M+], 233 (91), 205 (100), 189 (32), 172
(26), 158 (28), 129 (19), 117 (16), 102 (40).
CI–MS: m/z (%) = 263 (100) [MH+], 217 (26).
HRMS: m/z [MH+] calcd for C15H23N2S: 263.1576; found:
EI–MS: m/z (%) = 370 (1) [M+], 188 (29), 173 (23), 105 (100), 77
(81), 51 (25).
263.1575.
CI–MS: m/z (%) = 371 (100) [MH+], 353 (12).
HRMS: m/z [MH+] calcd for C24H23N2O2: 371.1754; found:
2-Butyl-4-(methylthio)-2-propyl-1,2-dihydroquinazoline (37)
Mp 35–36 °C.
371.1757.
1H NMR (CDCl3): d = 7.28 (dd, J = 1, 8 Hz, 1 H, H-5), 7.03 (app.
dt, J = 1, 8 Hz, 1 H, H-7), 6.49 (app. dt, J = 1, 8 Hz, 1 H, H-6), 6.33
(br d, J = 8 Hz, 1 H, H-8), 3.68 (br s, exch., 1 H, NH), 2.31 (s, 3 H,
SCH3), 1.68–1.61 (m, 2 H, CH2), 1.53–1.45 (m, 2 H, CH2), 1.41–
1.13 (m, 6 H, 3 × CH2), 0.82, 0.80 (2 × overlap. t, J = 7.5 Hz, 6 H,
2 × CH3).
13C NMR (CDCl3): d = 159.4 (s, C-4), 144.4 (s, C-8a), 132.9 (d, C-
7), 125.4 (d, C-5), 117.0 (d, C-6), 116.2 (s, C-4a), 113.6 (d, C-8),
75.8 (s, C-2), 44.2 (t, CH2), 41.5 (t, CH2), 26.3 (t, CH2), 23.4 (t,
CH2), 17.4 (t, CH2), 14.9 (q, CH3), 14.6 (q, CH3), 12.5 (q, CH3).
2-(1-Deuteriopropyl)-4-methoxyquinazoline (34)
Oil.
1H NMR (CDCl3): d = 8.00 (dd, J = 1, 8 Hz, 1 H, H-8), 7.81 (br d,
J = 8 Hz, 1 H, H-5), 7.68 (app. dt, J = 1, 8 Hz, 1 H, H-7), 7.36 (app.
dt, J = 1, 8 Hz, 1 H, H-6), 4.08 (s, 3 H, OCH3), 2.99 (m, 1 H, CHD),
1.88 (app. quin, J = 7.5 Hz, 2 H, CH2), 1.00 (t, J = 7.5 Hz, 3 H, CH3).
13C NMR (CDCl3): d = 167.2 (s, C-4), 167.1 (s, C-2), 151.6 (s, C-
8a), 133.5 (d, C-7), 127.4 (d, C-8), 126.2 (d, C-6), 123.6 (d, C-5),
115.0 (s, C-4a), 54.2 (q, OCH3), 41.8 [t (1:1:1), d, CHD], 22.1 (t,
CH2), 14.3 (q, CH3).
EI–MS: m/z (%) = 276 (5) [M+], 233 (100), 219 (93), 203 (19), 190
(24), 189 (44), 176 (40), 158 (55), 143 (18), 129 (20), 117 (15), 102
(17), 41 (69).
EI–MS: m/z (%) = 203 (5) [M+], 188 (40), 175 (100), 161 (18), 146
(22), 129 (12), 119 (20), 102 (31), 90 (22), 76 (21), 42 (29).
CI–MS: m/z (%) = 204 (100) [MH+], 175 (8).
HRMS: m/z [MH+] calcd for C12H14DN2O: 204.1242; found:
CI–MS: m/z (%) = 277 (100) [MH+], 231 (5), 219 (4).
HRMS: m/z [MH+] calcd for C16H25N2S: 277.1733; found:
277.1733.
204.1243.
Synthesis 2005, No. 17, 2951–2961 © Thieme Stuttgart · New York