1596
M. A. Matulenko et al. / Bioorg. Med. Chem. 15 (2007) 1586–1605
MeOH–CH2Cl2) provided 152 mg (69%) of 5f: orange
solid. H NMR (300 MHz, DMSO-d6) d 8.28 (s, 1H,
130.3 (d), 120.8 (s), 119.2 (s), 112.2 (d), 111.7 (d),
107.1 (s), 95.0 (s), 86.8 (s), 40.0 (q), 39.6 (q). MS
(DCI/NH3) m/z 358 (M+H)+. Anal. Calcd for
C22H23N5Æ0.2H2O: C, 73.18; H, 6.53; N, 19.40. Found:
C, 73.15; H, 6.37; N, 19.10.
1
@N–CH@N), 7.34 (AA0BB0, 2H, J = 8.5, ArH), 7.30
(AA0BB0, 2H, J = 7.8, ArH), 6.98 (AA0BB0, 2H, J = 8.8,
ArH), 6.64 (AA0BB0, 2H, J = 8.8, ArH), 6.40 (br s, 2H,
NH2), 2.93 (s, 6H, N(CH3)2), 2.40 (s, 3H, ArCH3). 13C
NMR (75 MHz, DMSO-d6) d 161.1 (s), 156.7 (d), 150.5
(s), 146.5 (s), 137.2 (s), 132.6 (d), 130.9 (s), 129.6 (d),
129.1 (d), 118.8 (s), 111.6 (d), 106.9 (s), 95.5 (s), 86.3 (s),
39.5 (q), 20.9 (q). MS (DCI/NH3) m/z 329 (M+H)+. Anal.
Calcd for C21H20N4Æ0.6H2OÆ0.1CH2Cl2: C, 72.88; H,
6.20; N, 16.11. Found: C, 73.15; H, 5.81; N, 15.78.
5.2.12. 5-Benzo[1,3]dioxol-5-yl-6-(4-dimethylaminophen-
ylethynyl)pyrimidin-4-ylamine (5j). Starting with 4j, the
title compound was prepared according to the general
procedure described for the aminolysis reaction (method
A). Aqueous work up and purification by chromatogra-
phy (elution with 50% EtOAc–hexane then 10% MeOH–
CH2Cl2) provided 112 mg (51%) of 5j: yellow solid; Rf
0.12 (50% EtOAc–hexane). 1H NMR (300 MHz,
CDCl3) d 8.49 (s, 1H, @N–CH@N), 7.19 (AA0BB0,
2H, J = 8.8, ArH), 6.96 (m, 3H, ArH), 6.57 (AA0BB0,
2H, J = 9.2, ArH), 6.06 (s, 2H, OCH2O), 5.06 (br s,
2H, NH2), 2.98 (s, 6H, N(CH3)2). 13C NMR
(100 MHz, DMSO-d6) d 161.3 (s), 156.7 (d), 150.6 (s),
147.4 (s), 146.9 (s), 146.6 (s), 132.7 (d), 127.4 (s), 123.5
(d), 118.7 (s), 111.7 (d), 110.2 (d), 108.6 (d), 106.9 (s),
101.0 (t), 95.7 (s), 86.3 (s), 39.5 (q). MS (DCI/NH3) m/
z 359 (M+H)+. Anal. Calcd for C21H18N4O2Æ0.20H2Oꢁ
0.30EtOAc: C, 68.65; H, 5.40; N, 14.42. Found: C,
68.74; H, 5.21; N, 14.48.
5.2.9. 6-(4-Dimethylaminophenylethynyl)-5-(4-methoxy-
phenyl)pyrimidin-4-ylamine (5g). Starting with 4g, the ti-
tle compound was prepared according to the general
procedure described for the aminolysis reaction (meth-
od A). Aqueous work up and purification by chroma-
tography (5% MeOH–CH2Cl2) gave 243 mg (70%) of
5g: yellow solid. 1H NMR (300 MHz, DMSO-d6) d
8.27 (s, 1H, @N–CH@N), 7.34 (AA0BB0, 2H, J = 8.8,
ArH), 7.08 (AA0BB0, 2H, J = 8.8, ArH), 7.01 (AA0BB0,
2H, J = 9.2, ArH), 6.65 (AA0BB0, 2H, J = 9.2, ArH),
6.42 (br s, 2H, NH2), 3.83 (s, 3H, OCH3), 2.93 (s,
6H, N(CH3)2). 13C NMR (75 MHz, DMSO-d6) d
161.3 (s), 159.0 (s), 156.6 (d), 150.6 (s), 146.6 (s),
132.6 (d), 131.1 (d), 125.9 (s), 118.7 (s), 114.1 (d),
111.7 (d), 106.9 (s), 95.5 (s), 86.4 (s), 55.2 (q), 39.5
(q). MS (DCI/NH3) m/z 345 (M+H)+. Anal. Calcd
for C21H20N4O: C, 73.23; H, 5.85; N, 16.27. Found:
C, 72.88; H, 5.81; N, 15.89.
5.2.13. 6-(4-Dimethylaminophenylethynyl)-5-(4-isopro-
pylphenyl)pyrimidin-4-ylamine (5k). Starting with 4k,
the title compound was prepared according to the gener-
al procedure described for the aminolysis reaction
(method A) followed by filtration to afford 225 mg
(60%) of 5k: orange solid. 1H NMR (300 MHz,
DMSO-d6) d 8.29 (s, 1H, @N–CH@N), 7.40 (AA0BB0,
2H, J = 8.1, ArH), 7.32 (AA0BB0, 2H, J = 8.1, ArH),
6.92 (AA0BB0, 2H, J = 8.8, ArH), 6.59 (AA0BB0, 2H,
J = 9.1, ArH), 6.43 (br s, 2H, NH2), 2.99 (m, 1H,
CH(CH3)2), 2.92 (s, 6H, N(CH3)2), 1.29 (d, 6H,
J = 6.8, CH(CH3)2). 13C NMR (100 MHz, DMSO-d6)
d 161.0 (s), 156.7 (d), 150.5 (s), 148.1 (s), 146.8 (s),
132.6 (d), 131.4 (s), 129.8 (d), 126.5 (d), 119.0 (s),
111.5 (d), 106.9 (s), 95.8 (s), 86.5 (s), 39.5 (q), 33.3 (d),
23.8 (q). MS (DCI/NH3) m/z 357 (M+H)+. Anal. Calcd
for C23H24N4Æ0.4H2O: C, 75.96; H, 6.87; N, 15.41.
Found: C, 76.16; H, 6.82; N, 15.55.
5.2.10.
5-(3,4-Dimethoxyphenyl)-6-(4-dimethylamino-
phenylethynyl)pyrimidin-4-ylamine (5h). Starting with
4h, the title compound was prepared according to the
general procedure described for the aminolysis reaction
(method A) followed by filtration to provide 210 mg
(62%) of 5h: light yellow solid. 1H NMR (300 MHz,
CDCl3) d 8.50 (s, 1H, @N–CH@N), 7.15 (AA0BB0,
2H, J = 9.2, ArH), 7.04 (m, 3H, ArH), 6.56 (AA0BB0,
2H, J = 9.2, ArH), 5.04 (br s, 2H, NH2), 3.97 (s, 3H,
OCH3), 3.88 (s, 3H, OCH3), 2.97 (s, 6H, N(CH3)2).
13C NMR (75 MHz, DMSO-d6) d 161.2 (s), 156.6 (d),
150.5 (s), 148.7 (s), 148.5 (s), 146.5 (s), 132.6 (d), 126.1
(s), 122.1 (d), 118.8 (s), 113.4 (d), 112.0 (d), 111.7 (d),
106.9 (s), 95.4 (s), 86.5 (s), 55.5 (q), 55.4 (q), 39.5 (q).
MS (DCI/NH3) m/z 375 (M+H)+. Anal. Calcd for
C22H22N4O2: C, 70.47; H, 6.03; N, 14.87. Found: C,
70.60; H, 5.92; N, 14.96.
5.2.14. 5-Cyclohexyl-6-(4-dimethylaminophenylethynyl)-
pyrimidin-4-ylamine (5l). Starting with 4l, the title
compound was prepared according to the general proce-
dure described for the aminolysis reaction (method A)
followed by filtration to afford 500 mg (59%) of 5l:
yellow solid. 1H NMR (400 MHz, DMSO-d6) d 8.14
(s, 1H, @N–CH@N), 7.39 (AA0BB0, 2H, J = 8.9,
ArH), 6.77 (AA0BB0, 2H, J = 8.9, ArH), 6.75 (br s,
2H, NH2), 2.97 (s, 6H, N(CH3)2), 2.94 (m, 1H, cyclohex-
yl-H), 2.25 (m, 2H, cyclohexyl-H), 1.83–1.71 (m, 3H,
cyclohexyl-H), 1.56 (m, 2H, cyclohexyl-H), 1.45–1.32
(m, 3H, cyclohexyl-H). 13C NMR (100 MHz, DMSO-
d6) d 161.6 (s), 155.2 (d), 150.7 (s), 145.6 (s), 132.2 (d),
121.5 (s), 112.0 (d), 107.3 (s), 95.7 (s), 87.0 (s), 39.6
(q), 36.4 (br d), 28.6 (t), 26.4 (t), 25.4 (t). MS (DCI/
NH3) m/z 321 (M+H)+. Anal. Calcd for C20H24N4Æ0.6-
H2OÆ0.5 EtOH: C, 71.20; H, 8.02; N, 15.81. Found: C,
71.14; H, 7.66; N, 15.74.
5.2.11. 5-(4-Dimethylaminophenyl)-6-(4-dimethylamino-
phenylethynyl)pyrimidin-4-ylamine (5i). Starting with 4i,
the title compound was prepared according to the gener-
al procedure described for the aminolysis reaction
(method A) followed by aqueous work up and triturat-
ing with Et2O to provide 150 mg (50%) of 5i: yellow sol-
1
id. H NMR (300 MHz, DMSO-d6) d 8.24 (s, 1H, @N–
CH@N), 7.25 (AA0BB0, 2H, J = 8.5, ArH), 7.05
(AA0BB0, 2H, J = 8.9, ArH), 6.86 (AA0BB0, 2H,
J = 8.8, ArH), 6.64 (AA0BB0, 2H, J = 9.2, ArH), 6.39
(br s, 2H, NH2), 2.97 (s, 6H, N(CH3)2), 2.93 (s, 6H,
N(CH3)2). 13C NMR (100 MHz, DMSO-d6) d 161.4
(s), 156.2 (d), 150.5 (s), 150.0 (s), 146.3 (s), 132.7 (d),