Organic & Biomolecular Chemistry
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= 7.2 Hz), 6.53 (1 H, s), 3.55 (2 H, s), 2.47 (8 H, br s), 2.29 (6 H,
yl)amino)phenyl)benzamide 19. Purified by preparative TLC
s). 13C NMR (150 MHz, CDCl3): /ppm = 165.63 (C), 150.06
(C), 145.27 (C), 142.84 (C), 138.07 (C), 136.85 (C), 133.82
(CH), 133.49 (C), 133.02 (C), 131.57 (CH), 129.35 (CH), 127.47
(C), 126.98 (CH), 116.65 (CH), 114.94 (CH), 104.84 (CH),
104.36 (CH), 62.46 (CH2), 55.07 (CH2), 53.08 (CH2), 45.99
(CH3), 17.32 (CH3). IR: νmax = 3295w, 2935w, 2801w, 1650m,
1599m, 1561s, 1528s, 1508m cm-1. HRMS calculated for
C26H29N6O2, [M + H]+, 457.2352; found 457.2363, Δ = 2.4 ppm.
(89:10:1 CH2Cl2/MeOH/conc. NH3(aq)) to give the title compound
(24 mg, 24%) as an off-white solid; mp 152-155 °C dec. Rt 3.46,
m
[M + H]+
/ = 510.3. Rf 0.16 (94:5:1 CH2Cl2/MeOH/conc.
z
NH3(aq)). 1H NMR (600 MHz, CDCl3): /ppm = 9.24 (1 H, d, J =
1.8 Hz), 8.70 (1 H, dd, J = 4.8 and 1.5 Hz), 8.58 (1 H, d, J = 1.5
Hz), 8.53-8.50 (2 H, m), 7.92 (1 H, s), 7.83 (2 H, d, J = 8.0 Hz),
7.44-7.40 (3 H, m), 7.31 (1 H, dd, J = 8.2 and 1.5 Hz), 7.20 (1 H,
d, J = 8.2 Hz), 7.18 (1 H, d, J = 5.1 Hz), 7.04 (1 H, s), 3.54 (2 H,
s), 2.41 (2 H, t, J = 7.4 Hz), 2.34 (3 H, s), 2.31 (2 H, t, J = 7.4
Hz), 2.23 (6 H, s), 2.20 (3 H, s), 1.70 (2 H, app quintet, J = 7.4
Hz). 13C NMR (150 MHz, CDCl3): /ppm = 165.43 (C), 162.75
(C), 160.58 (C), 159.01 (CH), 151.47 (CH), 148.49 (CH), 143.59
(C), 137.78 (C), 136.61 (C), 134.94 (CH), 133.75 (C), 132.68
(C), 130.76 (CH), 129.15 (CH), 126.97 (CH), 124.18 (C), 123.72
(CH), 115.30 (CH), 113.13 (CH), 108.34 (CH), 61.98 (CH2),
57.78 (CH2), 55.63 (CH2), 45.49 (CH3), 42.26 (CH3), 25.67
(CH2), 17.65 (CH3). IR: νmax = 3215w, 2940w, 2767w, 1655w,
1575s, 1526s, 1504s cm-1. HRMS calculated for C30H36N7O, [M
+ H]+, 510.2981; found 510.2998, Δ = 3.3 ppm.
N-(3-((4-(4-fluorophenyl)-6-phenylpyrimidin-2-yl)amino)-4-
methylphenyl)-4-((4-methylpiperazin-1-yl)methyl)benzamide
17. Purified by column chromatography (9:1 CH2Cl2/MeOH) to
give the title compound (30 mg, 26%) as a pale yellow powder;
mp 228-231 °C dec. Rt 4.35, [M + H]+ m/z = 587.3. Rf 0.28 (9:1
1
CH2Cl2/MeOH). H NMR (600 MHz, CDCl3): /ppm = 8.87 (1
H, d, J = 1.5 Hz), 8.21 (2 H, dd, J = 8.6 and 5.4 Hz), 8.17-8.16 (2
H, m), 7.85 (1 H, s), 7.84 (2 H, d, J = 8.0 Hz), 7.54 (1 H, s), 7.51-
7.50 (3 H, m), 7.45 (2 H, d, J = 8.0 Hz), 7.25 (1 H, dd, J = 8.2
and 1.5 Hz), 7.19-7.15 (3 H, m), 7.09 (1 H, s), 3.58 (2 H, s), 2.53
(8 H, br s), 2.37 (3 H, s), 2.33 (3 H, s). 13C NMR (150 MHz,
CDCl3): /ppm = 165.96 (C), 165.14 (C), 164.69 (C), 164.46 (C,
d, J = 250.6 Hz), 160.52 (C), 142.42 (C), 138.40 (C), 137.48 (C),
136.51 (C), 133.98 (C), 133.65 (C, d, J = 3.2 Hz), 130.67 (CH),
130.58 (CH), 129.41 (CH, d, J = 8.5 Hz), 129.31 (CH), 128.79
(CH), 127.27 (CH), 126.95 (CH), 123.26 (C), 115.75 (CH, d, J =
22 Hz), 114.41 (CH), 112.52 (CH), 104.36 (CH), 62.43 (CH2),
N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-
yl)amino)phenyl)-4-(morpholinomethyl)benzamide
20.27
Purified by column chromatography (94:5:1 CH2Cl2/MeOH/conc.
NH3(aq)) to give the title compound (23 mg, 24%) as an off-white
solid; mp 213-216 °C (lit.25 210-212 °C). Rt 3.61, [M + H]+ m/z =
481.2. Rf 0.29 (94:5:1 CH2Cl2/MeOH/conc. NH3(aq)). 1H NMR
(500 MHz, CDCl3): /ppm = 9.24 (1 H, d, J = 1.8 Hz), 8.70 (1 H,
dd, J = 4.8 and 1.5 Hz), 8.59 (1 H, d, J = 1.6 Hz), 8.52-8.50 (2 H,
m), 7.90 (1 H, s), 7.84 (2 H, d, J = 8.0 Hz), 7.45 (2 H, d, J = 8.0
Hz), 7.42 (1 H, dd, J = 7.9 and 4.8 Hz), 7.31 (1 H, dd, J = 8.2 and
1.6 Hz), 7.21 (1 H, d, J = 8.2 Hz), 7.18 (1 H, d, J = 5.2 Hz), 7.04
(1 H, s), 3.72 (4 H, t, J = 4.3 Hz), 3.56 (2 H, s), 2.46 (4 H, app br
s), 2.35 (3 H, s). 13C NMR (150 MHz, CDCl3): /ppm = 165.31
(C), 162.76 (C), 160.57 (C), 159.01 (CH), 151.49 (CH), 148.52
(CH), 141.90 (C), 137.81 (C), 136.57 (C), 134.91 (CH), 134.05
(C), 132.66 (C), 130.78 (CH), 129.34 (CH), 127.04 (CH), 124.20
(C), 123.70 (CH), 115.26 (CH), 113.07 (CH), 108.36 (CH), 66.94
(CH2), 62.91 (CH2), 53.62 (CH2), 17.65 (CH3). IR: νmax = 3230w,
2932w, 2810w, 1663m, 1606m, 1580s, 1561s, 1526s cm-1.
HRMS calculated for C28H29N6O2, [M + H]+, 481.2352; found
481.2371, Δ = 3.9 ppm.
54.99 (CH2), 52.86 (CH2), 45.81 (CH3), 17.72 (CH3). IR: νmax
=
3454w, 3437w, 3299w, 2933w, 2794w, 1645m, 1600m, 1588m,
1575m, 1531s, 1511m cm-1. HRMS calculated for C36H36FN6O,
[M + H]+, 587.2935; found 587.2937, Δ = 0.3 ppm.
4-((4-Methyl-1,4-diazepan-1-yl)methyl)-N-(4-methyl-3-((4-
(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)benzamide 18.26
Purified by preparative TLC (89:10:1 CH2Cl2/MeOH/conc.
NH3(aq)) to give the title compound (25 mg, 25%) as an off-white
solid; mp 155-160 °C dec. Rt 3.43, [M + H]+ m/z = 508.3. Rf 0.17
(94:5:1 CH2Cl2/MeOH/conc. NH3(aq)). 1H NMR (600 MHz,
CDCl3): /ppm = 9.23 (1 H, d, J = 1.8 Hz), 8.70 (1 H, dd, J = 4.8
and 1.5 Hz), 8.58 (1 H, d, J = 1.5 Hz), 8.52-8.50 (2 H, m), 7.93 (1
H, s), 7.83 (2 H, d, J = 8.0 Hz), 7.46 (2 H, d, J = 8.0 Hz), 7.41 (1
H, dd, J = 7.8 and 4.8 Hz), 7.31 (1 H, dd, J = 8.2 and 1.5 Hz),
7.20 (1 H, d, J = 8.2 Hz), 7.17 (1 H, d, J = 5.2 Hz), 7.04 (1 H, s),
3.69 (2 H, s), 2.73-2.69 (4 H, m), 2.68 (2 H, t, J = 5.8 Hz), 2.62 (2
H, m), 2.37 (3 H, s), 2.34 (3 H, s), 1.82 (2 H, app quintet, J = 5.8
Hz). 13C NMR (150 MHz, CDCl3): /ppm = 165.45 (C), 162.73
(C), 160.58 (C), 159.01 (CH), 151.47 (CH), 148.50 (CH), 143.97
(C), 137.78 (C), 136.62 (C), 134.92 (CH), 133.71 (C), 132.67
(C), 130.76 (CH), 128.97 (CH), 126.97 (CH), 124.17 (C), 123.71
(CH), 115.30 (CH), 113.13 (CH), 108.33 (CH), 62.45 (CH2),
58.17 (CH2), 56.76 (CH2), 54.72 (CH2), 54.34 (CH2), 47.04
(CH3), 27.54 (CH2), 17.65 (CH3). IR: νmax = 3235w, 3032w,
2929w, 2800w, 1652m, 1575s, 1553s, 1526s, 1504s cm-1. HRMS
calculated for C30H34N7O, [M + H]+, 508.2825; found 508.2837,
Δ = 2.4 ppm.
N-(4-fluoro-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)-
4-((4-methylpiperazin-1-yl)methyl)benzamide 21.26 Purified by
column chromatography (MeOH). The fractions corresponding to
the product were combined and the solvent removed in vacuo.
The residue was dissolved in CH2Cl2 (5 mL), filtered and the
solvent removed in vacuo to give the title compound (35 mg,
35%) as an off-white solid; mp 186-189 °C. Rt 3.40, [M + H]+ m
/
z
1
= 498.3. Rf 0.11 (MeOH). H NMR (500 MHz, CDCl3): /ppm =
9.24 (1 H, d, J = 1.8 Hz), 8.96 (1 H, dd, J = 7.1 and 2.1 Hz), 8.70
(1 H, dd, J = 4.8 and 1.6 Hz), 8.60-8.58 (1 H, m), 8.54 (1 H, d, J
= 5.2 Hz), 7.88 (1 H, s), 7.83 (2 H, d, J = 8.2 Hz), 7.47-7.42 (4 H,
m), 7.29-7.26 (2 H, m), 7.09 (1 H, dd, J = 10.7 and 8.8 Hz), 3.57
(2 H, s), 2.53 (8 H, br s), 2.34 (3 H, s). 13C NMR (125 MHz,
CDCl3): /ppm = 165.37 (C), 162.82 (C), 159.83 (C), 158.94
(CH), 151.64 (CH), 149.07 (C, d, J = 241.2 Hz), 148.49 (CH),
4-(((3-(Dimethylamino)propyl)(methyl)amino)methyl)-N-(4-
methyl-3-((4-(pyridin-3-yl)pyrimidin-2-
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