2802
I. Cikotiene et al.
LETTER
157.9, 161.9, 172.2. Anal. Calcd for C18H18N4OS: C, 63.88;
H, 5.36; N, 16.56. Found: C, 63.96; H, 5.44; N, 16.70.
2-(Methylthio)-7-phenyl-4-piperidin-1-ylpyrido[4,3-d]-
pyrimidine (2c)
pressure, compounds 3a–c were isolated by column flash
chromatography.
N-{4-(Z)-2-[(tert-butylamino)-2-phenylvinyl]-2-(methyl-
thio)-6-morpholin-1-ylpyrimidin-5-ylmethylene}-2-
methylpropan-2-amine (3b)
Yield 62%, mp 140–142 °C (from MeOH–H2O); Rf = 0.78
(toluene–EtOAc, 1:1). IR (KBr): 3442 (NH) cm–1. 1H NMR
(300 MHz, CDCl3): d = 1.19 (9 H, s, t-Bu), 1.22 (9 H, s, t-
Bu), 2.57 (3 H, s, SCH3), 3.46 [4 H, t, J = 4.2 Hz, N(CH2)2],
3.79 [4 H, t, J = 4.2 Hz, O(CH2)2], 6.17 (1 H, s, CH), 7.34–
7.36 (3 H, m, ArH), 7.46–7.49 (2 H, m, ArH), 8.15 (1 H, s,
CH), 10.08 (1 H, br s, NH). 13C NMR (75 Hz, CDCl3):
d = 13.9, 29.5, 32.1, 49.8, 53.9, 57.7, 66.8, 96.3, 105.5,
127.3, 128.2, 128.8, 140.9, 153.4, 160.6, 162.2, 164.2,
168.0. Anal. Calcd for C26H37N5OS: C, 66.77; H, 7.97; N,
14.95. Found: C, 66.49; H, 8.08; N, 15.10.
Yield 85%, mp 126–128 °C (from 2-PrOH). 1H NMR (300
MHz, CDCl3): d = 1.84 [4 H, br s, (CH2)3], 2.65 (3 H, s,
SCH3), 3.94 [4 H, br s, N(CH2)2], 7.49–7.54 (3 H, m, ArH),
7.90 (1 H, s, CH), 8.13 (2 H, d, J = 6.9 Hz, ArH), 9.24 (1 H,
s, CH). 1H NMR (300 MHz, DMSO-d6): d = 1.74 [4 H, br s,
(CH2)3], 2.56 (3 H, s, SCH3), 3.92 [4 H, br s, N(CH2)2], 7.49–
7.54 (3 H, m, ArH), 7.94 (1 H, s, CH), 8.22–8.25 (2 H, m,
ArH), 9.25 (1 H, s, CH). 13C NMR (75 Hz, CDCl3): d = 14.2,
24.6, 26.0, 50.5, 115.3, 127.1, 128.8, 129.5, 138.4, 149.3,
157.2, 157.6, 161.7, 172.0. Anal. Calcd for C19H20N4S: C,
67.83; H, 5.99; N, 16.65. Found: C, 67.90; H, 6.07; N, 16.59.
4-N,N-Dimethylamino-2-(methylthio)-7-phenylpyrido-
[4,3-d]pyrimidine (2f)
(10) N-{4-(Z)-2-[(tert-butylamino)-2-phenylvinyl]-2-(methyl-
thio)-6-piperidin-1-ylpyrimidin-5-ylmethylene}-2-
methylpropan-2-amine (3c)
Yield 92%, mp 155–156 °C (from 2-PrOH). 1H NMR (300
MHz, CDCl3): d = 2.65 (3 H, s, SCH3), 3.51 [6 H, s,
N(CH3)2], 7.49–7.53 (3 H, m, ArH), 7.90 (1 H, s, CH), 8.13
(2 H, d, J = 7.2 Hz, ArH), 9.41 (1 H, s, CH). 13C NMR (75
Hz, CDCl3): d = 14.2, 41.8, 109.3, 115.3, 127.1, 128.8,
129.5, 138.4, 149.6, 157.2, 157.4, 160.8, 171.7. Anal. Calcd
for C16H16N4S: C, 64.84; H, 5.44; N, 18.90. Found: C, 64.79;
H, 5.32; N, 18.99.
Yield 58%, mp 109–110 °C (from 2-PrOH); Rf = 0.81
(toluene–EtOAc, 1:1). IR (KBr): 3443 (NH) cm–1. 1H NMR
(300 MHz, CDCl3): d = 1.17 (9 H, s, t-Bu), 1.23 (9 H, s, t-
Bu), 1.65 [6 H, br s, (CH2)3], 2.57 (3 H, s, SCH3), 3.41 [4 H,
br s, N(CH2)2], 6.31 (1 H, s, CH), 7.32–7.34 (3 H, m, ArH),
7.48–7.51 (2 H, m, ArH), 8.07 (1 H, s, CH), 9.98 (1 H, br s,
NH). 1H NMR (300 MHz, DMSO-d6): d = 1.09 (9 H, s, t-
Bu), 1.14 (9 H, s, t-Bu), 1.61 [6 H, br s, (CH2)3], 2.52 (3 H,
s, SCH3), 3.37 [4 H, br s, N(CH2)2], 6.50 (1 H, s, CH), 7.40
7-(4-Ethylphenyl)-2-(methylthio)-4-morpholin-1-yl-
pyrido-[4,3-d]pyrimidine (2l)
Yield 90%, mp 127–128 °C (from hexane). 1H NMR (300
MHz, CDCl3): d = 1.32 (3 H, t, J = 7.5 Hz, CH3), 2.63 (3 H,
s, SCH3), 2.76 (2 H, q, J = 7.5 Hz, CH2), 3.92 [4 H, t, J = 2.1
Hz, N(CH2)2], 3.96 [4 H, t, J = 2.1 Hz, O(CH2)2], 7.38 (2 H,
d, J = 8.1 Hz, ArH), 7.72 (1 H, s, CH), 7.79 (2 H, d, J = 8.1
Hz, ArH), 9.04 (1 H, s, CH). 13C NMR (75 Hz, CDCl3):
d = 14.3, 15.4, 28.7, 49.8, 66.7, 108.8, 114.5, 127.1, 128.4,
135.6, 146.2, 148.9, 157.1, 158.0, 161.9, 172.1. Anal. Calcd
for C20H22N4OS: C, 65.55; H, 6.05; N, 15.29. Found: C,
65.76; H, 5.93; N, 15.44.
(5 H, s, ArH), 7.99 (1 H, s, CH), 9.88 (1 H, br s, NH). 13
C
NMR (75 Hz, CDCl3): d = 13.9, 24.6, 26.1, 29.6, 32.1, 50.5,
53.9, 57.5, 97.3, 105.5, 127.3, 128.0, 128.9, 141.3, 153.9,
160.1, 161.9, 164.8, 167.7. Anal. Calcd for C27H39N5S: C,
69.63; H, 8.44; N, 15.04. Found: C, 69.42; H, 8.59; N, 15.19.
(11) Typical Procedure for the Cyclization of N-{4-[(Z)-2-
(tert-butylamino)-2-phenylvinyl]pyrimidin-5-yl-
methylene}-2-methylpropan-2-amines 3a–c into
4-Substituted 2-(Methylthio)-7-phenylpyrido[4,3-d]-
pyrimidines 2a–c
The solution of compounds 3a–c (2 mmol) in DMSO (2 mL)
was heated at 110–120 °C for 15 min. After cooling, reaction
mixture was diluted with H2O (10 mL), precipitate collected
by filtration and recrystallyzed to give compounds 2a–c.
(12) Compounds 2a,d–e,g–k,m–u and 3a were also fully
characterized by IR, 1H NMR, and 13C NMR spectroscopic
and microanalytical data.
(9) Typical Procedure for the Preparation of N-{4-[(Z)-2-
(tert-butylamino)-2-phenylvinyl]-2-(methylthio)-
pyrimidin-5-ylmethylene}-2-methylpropan-2-amines
3a–c
The mixture of the corresponding 2,4-disubstituted 6-
(arylethynyl)pyrimidine-5-carbaldehyde 1a–c (0.2 mmol)
and t-BuNH2 (3 mL) in tube was flushed with argon, and the
tube was carefully sealed. The mixture was heated at 80–
90 °C for 20 h. The solvent was evaporated under reduced
Synlett 2008, No. 18, 2799–2802 © Thieme Stuttgart · New York