M. McMullan et al. / European Journal of Medicinal Chemistry 123 (2016) 48e57
55
of DMF. The organic phase was dried over Na2SO4, filtered and
4.2.6. 2-Benzylamino-1-phenyl-1,4-dihydroquinazoline
hydrochloride (17b)
concentrated under reduced pressure. The crude product was pu-
rified by silica gel column chromatography, eluting in
CH2Cl2:CH3OH.
Following Method A and starting from 13b (1.0 eq., 25 mg,
0.08 mmol) the title compound was obtained as an off-white solid
(24 mg, 85%). Mp: 115e120 ꢁC. dH (400 MHz, CDCl3): 7.63 (m, 3H, CH
Ar), 7.37 (d, 2H, J ¼ 7.2 Hz, CH Ar), 7.25 (m, 5H, J ¼ 7.3 Hz, CH Ar), 7.10
(m, 3H, CH Ar), 6.16 (app. t, 1H, J ¼ 7.2 Hz, CH Ar), 4.86 (s, 4H, CH2-4,
CH2). dC (100 MHz, CDCl3): 151.1 (qC), 136.2 (qC Ar), 135.4 (qC Ar),
133.4 (qC Ar), 131.7 (CH Ar), 131.2 (CH Ar), 129.9 (qC Ar), 128.8 (CH
Ar), 128.1 (CH Ar), 127.8 (CH Ar), 126.4 (CH Ar), 125.9 (CH Ar), 125.2
(CH Ar), 119.3 (CH Ar), 115.5 (CH Ar), 47.1 (CH2), 41.5 (CH2). vmax
(ATR)/cmꢀ1: 3290 (NH), 2925, 1641, 1602, 1558, 1490, 1357, 13,26,
1244, 1207, 1072, 1028, 752. HRMS (m/z ESIþ): Found: 314.1659
(Mþ þ H, C21H20N3 Requires: 314.1651). Purity by HPLC: 99.3% (tR
29.17 min).
4.2.2. 2-Amino-1-propyl-1,4-dihydroquinazoline hydrochloride
(6a)
Following Method A and starting from 15a (1.0 eq., 20 mg,
0.11 mmol) the title compound was obtained as a yellow solid
(21 mg, 85%). Mp: 210e214 ꢁC, decomposed. dH (400 MHz, D2O):
7.29e7.21 (m, 1H, CH Ar), 7.09 (m, 3H, CH Ar), 4.27 (s, 2H, CH2), 3.65
(m, 2H, CH2), 1.60 (m, 2H, CH2), 0.93 (t, 3H, J ¼ 7.4 Hz, CH3). dC
(100 MHz, D2O): 149.1 (qC), 133.9 (qC Ar), 128.5 (CH Ar), 126.1 (CH
Ar), 125.1 (CH Ar), 121.8 (qC Ar), 115.4 (CH Ar), 46.2 (CH2), 40.4
(CH2), 19.6 (CH2), 9.64 (CH3). vmax (ATR)/cmꢀ1: 3276 (NH), 2941,
1648, 1601, 1575, 1512, 1392, 1243, 1149, 1020, 795, 691. HRMS (m/z
ESIþ): Found: 190.1359 (Mþ þ H, C11H16N3 Requires: 190.1338).
Purity by HPLC: 97.6% (tR 24.19 min).
4.2.7. 1-(1,3-Benzodioxolyl-5-methyl)-2-benzylamino-1,4-
dihydroquinazoline hydrochloride (17c)
Following Method A and starting from 13c (1.0 eq., 45 mg,
0.12 mmol) the title compound was obtained as a yellow solid
(43 mg, 88%). Mp: 98e103 ꢁC. dH (400 MHz, CDCl3): 10.01 (br s, 1H,
NH), 8.09 (br s, 1H, NH), 7.17 (m, 6H, CH Ar), 7.07 (m, 2H, CH Ar),
6.94 (m, 1H, CH Ar), 6.66 (br s, 1H, CH Ar), 6.58 (m, 2H, CH Ar), 5.90
(s, 2H, CH2), 5.21 (s, 2H, CH2), 4.70 (d, 2H, J ¼ 4.9 Hz, CH2), 4.44 (d,
2H, J ¼ 5.1 Hz, CH2). dC (100 MHz, CDCl3): 151.2 (qC), 148.1 (qC Ar),
147.0 (qC Ar), 141.2 (qC Ar), 138.2 (qC Ar), 138.0 (qC Ar), 129.3 (qC
Ar), 128.4 (CH Ar), 127.7 (CH Ar), 126.8 (CH Ar), 125.5 (CH Ar), 124.0
(CH Ar), 123.6 (CH Ar), 119.8 (CH Ar), 114.9 (CH Ar), 108.4 (CH Ar),
106.8 (CH Ar), 101.1 (CH2), 48.9 (CH2), 46.7 (CH2), 43.4 (CH2). vmax
(ATR)/cmꢀ1: 3211 (NH), 2957, 1632, 1600, 1598, 1488, 1444, 1358,
1236, 1170, 1095, 1053, 921, 908, 751. HRMS (m/z ESIþ): Found:
372.1714 (Mþ þ H, C23H22N3O2 Requires: 372.1706). Purity by HPLC:
97.3% (tR 28.64 min).
4.2.3. 2-Amino-1-phenyl-1,4-dihydroquinazoline hydrochloride
(6b)
Following Method A and starting from 15b (1.0 eq., 19 mg,
0.08 mmol) the title compound was obtained as a yellow solid
(19 mg, 91%). Mp: 240e250 ꢁC, decomposed. dH (400 MHz, D2O):
7.67 (m, 3H, CH Ar), 7.36 (d, 2H, J ¼ 7.7 Hz, CH Ar), 7.05e7.16 (m, 3H,
CH Ar), 6.20 (m, 1H, CH Ar), 4.73 (s, 2H, CH2). dC (100 MHz, CH3OH):
153.0 (qC), 136.0 (qC Ar), 133.9 (qC Ar), 131.1 (CH Ar), 130.8 (CH Ar),
129.5 (CH Ar), 128.5 (qC Ar), 126.1 (CH Ar), 125.0 (CH Ar), 118.9 (CH
Ar), 115.9 (CH Ar), 40.6 (CH2). vmax (ATR)/cmꢀ1: 3337 (NH), 3249
(NH), 2934, 2858, 1643, 1600, 1492, 1421, 1345, 1286, 1143, 1026,
761, 705. HRMS (m/z ESIþ): Found: 224.1188 (Mþ þ H, C14H14N3
Requires: 224.1182). Purity by HPLC: 98.7% (tR 24.16 min).
4.2.4. 2-Amino-1-propyl-1,4-dihydropyrido[2,3-d]pyrimidine
hydrochloride (7a)
4.2.8. 2-Benzylamino-1-propyl-1,4-dihydropyrido[2,3-d]
Following Method A and starting from 16a (1.0 eq., 17 mg,
0.09 mmol) the title compound was obtained as a yellow solid
(15 mg, 74%). Mp: 211e220 ꢁC, decomposed. dH (400 MHz, D2O):
8.10 (m, 1H, CH Ar), 7.49 (app. t, 1H, J ¼ 7.1 Hz, CH Ar), 7.09 (dd, 1H,
J ¼ 7.1 Hz, 4.8 Hz, CH Ar), 4.40 (s, 2H, CH2), 3.85 (t, 2H, J ¼ 6.7 Hz,
CH2), 1.58 (m, 2H, CH2), 0.80 (t, 3H, J ¼ 6.7 Hz, CH3). dC (100 MHz,
CH3OH): 159.5 (qC), 154.2 (qC Ar), 134.8 (CH Ar), 145.9 (CH Ar),
120.6 (CH Ar), 115.1 (qC Ar), 43.5 (CH2), 39.9 (CH2), 20.5 (CH2), 9.5
(CH3). vmax (ATR)/cmꢀ1: 3268 (NH), 2962, 2933, 2917, 1624, 1595,
1335, 1234, 1155, 1138, 1002, 957, 903, 863, 757, 789, 732. HRMS (m/
z ESIþ): Found: 191.1289 (Mþ þ H, C10H15N4 Requires: 191.1291).
Purity by HPLC: 95.3% (tR 22.84 min).
pyrimidine hydrochloride (18a)
Following Method A and starting from compound 14a (1.0 eq.,
50 mg, 0.17 mmol) the title compound was obtained as a yellow
solid (47 mg, 87%). Mp: 113e117 ꢁC. dH (400 MHz, CDCl3): 9.27 (br s,
2H, NH), 8.18 (d, 1H, J ¼ 7.3 Hz, CH Ar), 7.59 (d, 1H, J ¼ 7.3 Hz, CH Ar),
7.26 (d, 2H, J ¼ 7.1 Hz, CH Ar), 7.16 (t, 2H, J ¼ 7.1 Hz, CH Ar), 7.10 (d,
1H, J ¼ 7.1 Hz, CH Ar), 6.96 (app. t, 1H, J ¼ 7.0 Hz, CH Ar), 4.86 (s, 2H,
CH2), 4.49 (s, 2H, CH2), 4.31 (t, 2H, J ¼ 7.1 Hz, CH2), 1.65 (m, 2H, CH2),
0.91 (t, 3H, J ¼ 7.0 Hz, CH3). dC (100 MHz, CDCl3): 152.0 (qC), 147.4 (q
Ar), 147.2 (CH Ar), 136.2 (CH Ar), 134.2 (qC Ar), 127.6e128.4 (5 CH
Ar), 120.1 (CH Ar), 115.5 (qC Ar), 45.2 (CH2), 44.0 (CH2), 40.2 (CH2),
21.6 (CH2), 10.8 (CH3). vmax (ATR)/cmꢀ1: 3044 (NH), 2923, 1719,
1653, 1556, 1549, 1423, 1361, 1330, 1257, 1116, 1050, 1018, 897, 763.
HRMS (m/z ESIþ): Found: 281.17,588 (Mþ þ H, C17H21N4 Requires:
281.1760). Purity by HPLC: 95.5% (tR 27.29 min).
4.2.5. 2-Benzylamino-1-propyl-1,4-dihydroquinazoline
hydrochloride (17a)
Following Method A and starting from 13a (1.0 eq., 140 mg,
0.5 mmol) the title compound was obtained as a yellow solid
(137 mg, 86%). Mp: 124e130 ꢁC. dH (400 MHz, CDCl3): 9.27 (br s, 1H,
NH), 9.10 (br s, 1H, NH), 7.46 (d, 2H, J ¼ 7.3 Hz, CH Ar), 7.20 (t, 3H,
J ¼ 7.3 Hz, CH Ar), 7.10 (m, 1H, CH Ar), 7.05 (app. t, 1H, J ¼ 7.4 Hz, CH
Ar), 6.99 (app. t, 1H, J ¼ 7.4 Hz, CH Ar), 6.82 (d, 1H, J ¼ 7.4 Hz, CH Ar),
4.72 (d, 2H, J ¼ 5.2 Hz, CH2), 4.31 (s, 2H, CH2), 4.04 (t, 2H, J ¼ 7.3 Hz,
CH2), 1.62 (m, 2H, CH2), 0.75 (t, 3H, J ¼ 7.3 Hz, CH3). dC (100 MHz,
CDCl3): 153.3 (qC), 152.6 (qC Ar), 137.2 (qC Ar), 128.4 (qC Ar), 128.0
(CH Ar), 127.5 (CH Ar), 125.6 (CH Ar), 124.3 (CH Ar), 123.9 (CH Ar),
115.4 (CH Ar), 49.6 (CH2), 47.2 (CH2), 41.7 (CH2), 20.4 (CH2), 10.5
(CH3). vmax (ATR)/cmꢀ1: 3100 (NH), 2959, 1657, 1602, 1566, 1482,
1404, 1395, 1278, 1253, 1176, 1063, 1029, 795. HRMS (m/z ESIþ):
Found: 280.1805 (Mþ þ H, C18H22N3 Requires: 280.1808). Purity by
HPLC: 99.1% (tR 28.39 min).
4.2.9. 2-Benzylamino-1-hydroxyethyl-1,4-dihydropyrido[2,3-d]
pyrimidine hydrochloride (18b)
Following Method A and starting from 14b (1.0 eq., 30 mg,
0.11 mmol) the title compound was obtained as a white solid
(26 mg, 74%). Mp: 148e151 ꢁC. dH (400 MHz, CDCl3): 9.62 (br s, 1H,
NH), 9.33 (br s, 1H, NH), 8.13 (d, 1H, J ¼ 7.1 Hz, CH Ar), 7.38 (d, 1H,
J ¼ 7.1 Hz, CH Ar), 7.27 (d, 2H, J ¼ 7.0 Hz, CH Ar), 7.20 (t, 2H,
J ¼ 7.1 Hz, CH Ar), 7.13 (t, 1H, J ¼ 7.1 Hz, CH Ar), 6.97 (app. t, 1H,
J ¼ 7.0 Hz, CH Ar), 4.71 (s, 2H, CH2), 4.44 (s, 2H, CH2), 4.32 (t, 2H,
J ¼ 6.9 Hz, CH2), 4.02 (t, 2H, J ¼ 6.9 Hz, CH2). dC (100 MHz, CDCl3):
153.5 (qC), 148.8 (qC Ar), 146.1 (CH Ar), 135.3 (CH Ar), 134.2 (qC Ar),
128.7 (CH Ar), 127.9 (CH Ar), 127.8, (CH Ar), 120.4 (qC Ar), 115.7 (CH
Ar), 60.9 (CH2), 48.1 (CH2), 46.3 (CH2), 40.4 (CH2). vmax (ATR)/cmꢀ1
3229 (NH), 2947,1673,1598,1567,1434,1497,1358,1311,1079,1050,
: