Supplementary material
2,6,8-Trisubstituted-1-Deazapurines as Adenosine Receptor Antagonists.
Lisa C. W. Chang, Jacobien Frijtag Drabbe Künzel*, Thea Mulder-Krieger, Joost Westerhout, Thomas Spangenberg, Johannes Brussee, Adriaan P. IJzerman
Contents: • •
experimental and spectroscopic data of compounds 6-12, 14 elemental analyses of compounds 1-14
S1
Experimental and spectroscopic data of compounds 6-12, 14
2,6-Diphenyl-8-methyl-1-deazapurine (6) Yield 87 %. mp 188-192 ºC; 1H NMR δ(CDCl3): 8.16-8.03 (m, 4H, Ph), 7.77 (s, 1H C1-H), 7.597.47 (m, 6H, Ph), 2.01 (s, 3H, CH3). 13C-NMR δ(CDCl3): 153.9, 151.8, 150.5, 140.3, 139.6, 136.3, 133.1, 129.0, 128.8, 128.6, 127.7, 114.6, 14.9. MS (ES+): 286.0 Da. 2,6-Diphenyl-8-ethyl-1-deazapurine (7) Yield 36 %. mp 188-192 ºC; 1H NMR δ(CDCl3 + MeOD): 7.93-7.87 (m, 4H, Ph), 7.62 (s, 1H C1H), 7.42-7.36 (m, 6H, Ph), 2.72 (q, 2H, J = 7.3 Hz, CH2), 1.22 (t, 3H, J = 7.3 Hz, CH3). 13C-NMR δ(CDCl3 + MeOD): 159.1, 152.1, 139.8, 136.0, 130.8, 128.7, 128.6, 128.5, 128.3, 127.1, 114.7, 22.5,
12.0. MS (ES+): 300.0 Da. 2,6-Diphenyl-8-propyl-1-deazapurine (8) Yield 29 %. mp 156-158 ºC; 1H NMR δ(MeOD): 8.05-8.04 (m, 2H, Ph), 8.00-7.89 (m, 2H, Ph), 7.70 (s, 1H C1-H), 7.54-7.35 (m, 6H, Ph), 2.88 (t, 2H, J = 7.3 Hz, CH2), 1.88 (m, 2H, CH2), 1.01 (t, 3H, J = 7.3 Hz, CH3). 13C-NMR δ(CDCl3): 153.4, 151.6, 150.0, 141.3, 137.4, 129.7, 129.4, 128.0, 115.3, 31.8, 22.6, 13.8. MS (ES+): 314.0 Da. 2,6-Diphenyl-8-isopropyl-1-deazapurine (9) Yield 71 %. mp 232-234 ºC; 1H NMR δ(MeOD + CDCl3): 8.01-7.99 (m, 2H, Ph), 7.97-7.87 (m, 2H, Ph), 7.66 (s, 1H C1-H), 7.49-7.37 (m, 6H, Ph), 3.29-3.22 (m, 1H, CH), 1.43 (d, 6H, J = 7.3 Hz, 2 × CH3). 13C-NMR δ(DMSO): 162.1, 150.4, 150.2, 139.6, 137.1, 136.1, 131.6, 129.1, 128.7, 128.5, 128.3, 126.7, 112.2, 29.0, 21.1. MS (ES+): 314.0 Da. 2,6-Diphenyl-8-isobutyl-1-deazapurine (10) Yield 65 %. mp 179-181 ºC; 1H NMR δ(CDCl3): 8.22-8.19 (m, 2H, Ph), 8.10-8.06 (m, 2H, Ph), 7.80 (s, 1H C1-H), 7.55-7.44 (m, 6H, Ph), 2.24 (d, 2H, J = 7.3 Hz, CH2), 1.86-1.80 (m, 1H, CH), 0.64 (d, 6H, J = 5.8 Hz, 2 × CH3).
13
C-NMR δ(CDCl3): 157.2, 151.7, 150.4, 140.4, 139.5, 136.3,
133.1, 129.2, 128.7, 17.7, 114.6, 38.1, 22.1. MS (ES+): 328.0 Da.
S2
2,6-Diphenyl-8-(1-ethylpropyl)-1-deazapurine (11) Yield 39 %. mp 196-197 ºC; 1H NMR δ(CDCl3): 8.27-8.24 (m, 2H, Ph), 8.11-8.07 (m, 2H, Ph), 7.82 (s, 1H C1-H), 7.57-7.43 (m, 6H, Ph), 2.37-2.30 (m, 1H, CH), 1.53-1.43 (m, 4H, 2 × CH2), 0.700.63 (m, 6H, 2 × CH3). 13C-NMR δ(CDCl3): 160.3, 151.8, 150.0, 140.4, 139.2, 136.4, 132.7, 129.3, 128.9, 128.8, 128.5, 127.5, 114.3, 43.5, 26.6, 11.7. MS (ES+): 342.0 Da. 2,6-Diphenyl-8-tButyl-1-deazapurine (12) Yield 76 %. mp 233-234 ºC; 1H NMR δ(CDCl3): 8.33-8.29 (m, 2H, Ph), 8.01-7.98 (m, 2H, Ph), 7.82 (s, 1H C1-H), 7.55-7.41 (m, 6H, Ph), 1.44 (s, 9H, 3 × CH3). 13C-NMR δ(CDCl3): 163.8, 152.1, 150.1, 140.2, 139.0, 138.2, 136.2, 132.3, 129.3, 128.9, 128.8, 128.7, 128.4, 128.3, 127.4, 114.1, 33.6, 28.9. MS (ES+): 328.0 Da. Cyclohexane carboxylic anhydride12 Cyclohexane carboxylic acid (1.24 mL, 10 mmol) was ground together with K2CO3 (6 g) for approx. 5 min. Tosyl chloride (0.95 g, 5 mmol, 0.5 eq.) was then added portionwise with a few drops of EtOAc. Grinding was continued for approx. 40 min. The solids were then washed with CH2Cl2 (3 × 20 mL), filtered and the filtrate concentrated. Yield 26 %. 1H NMR δ(CDCl3): 2.46-2.33 (m, 2H, CH), 1.99-1.23 (m, 20H, cHex). 2,6-Diphenyl-8-cyclohexyl-1-deazapurine (14) Yield 49 %. mp 210-213 ºC; 1H NMR δ(CDCl3): 8.32-8.22 (m, 2H, Ph), 8.11-8.08 (m, 2H, Ph), 7.83 (s, 1H C1-H), 7.55-7.45 (m, 6H, Ph), 2.51-2.44 (m, 1H, CH), 1.10-1.06 (m, 10 H, cHex). 13CNMR δ(CDCl3): 161.4, 151.8, 150.2, 140.2, 139.4, 136.4, 129.3, 129.0, 128.8, 128.6, 127.5, 114.3, 38.6, 31.3, 25.7. MS (ES+): 354.0 Da.
S3
H 7.04 8.06 5.03 5.08 5.35 5.26 5.87 6.43 5.93 6.61 6.69 6.39 6.54 6.93
69.89 65.02 73.97 78.04 82.50 79.32 78.14 79.19 78.01 78.27 79.73 79.74 76.36 79.88
1
2
3
4
5
6
7
8
9
10
11
12
13
14
N
11.21
11.62
12.66
12.10
12.95
12.94
12.80
13.67
14.59
12.15
15.69
13.82
21.26
22.23
Theoretical in % C
Compounds
Elemental Analyses of Compounds 1-14
79.82
76.31
79.73
79.70
78.21
77.99
79.33
78.08
79.30
82.41
78.06
73.95
65.35
69.70
C
7.17
6.37
6.77
6.98
6.47
6.13
6.49
6.03
5.49
5.46
5.21
4.64
8.55
7.01
H
11.47
11.88
12.57
12.10
12.74
12.99
12.52
14.07
14.63
12.05
15.64
13.60
21.60
22.61
N
Experimental in %
0.06
0.05
0.01
0.03
0.06
0.02
-0.14
0.06
0.02
0.09
-0.02
0.02
-0.33
0.19
C
-0.24
0.17
-0.38
-0.29
0.14
-0.20
-0.06
-0.16
-0.23
-0.11
-0.13
0.39
-0.49
0.03
H
N
-0.26
-0.26
0.09
0.00
0.21
-0.05
0.28
-0.40
-0.04
0.10
0.05
0.22
-0.34
-0.38
Deviation in %
C24H23N3•0.5EtOH
C23H21N3•0.1H2O
C22H21N3•0.04CHCl3
C23H23N3•0.05CHCl3
C22H21N3•0.6H2O
C21H19N3•0.10CHCl3
C21H19N3•0.3EtOH
C20H17N3•0.4H2O
C19H15N3•0.02CHCl3
C25H19N3•0.2CH3CN
C18H13N3•0.2DMF
C18H13N3O•0.4EtOH
C10H13N3•0.7MeOH
C11H13N3•0.1H2O
Molecular Formula
S4
