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(C-2‴), 119.92 (C-2″), 121.03 (C-4‴), 128.25 (C-3″), 128.49 (C-4″),
128.57 (C-3‴), 138.63 (C-8′), 141.30 (C-1‴), 144.53 (C-1″), 151.60
(C-2′, C-4′), 155.16 (C-6′). NegESI MS m/z (%): 558.2 (100) [M-H];
HRMS negESI (C28H37O3N8S) calculated: 565.27148; found:
565.27112.
9-cyclohexyl-N2-phenyl-N6-(4-[pyrrolidin-1-ylsulfonyl]phenyl)-9H-
purine-2,6-diamine ((24b): Aniline (33 μL) was used in the second stage
pf reaction, FCC in 1-3% MeOH in CHCl3, yield 48 mg (34%). 1H
6″), 139.13 (C-8), 140.42 (C-3″), 143.95 (C-1′), 150.29 (C-4), 151.64
(C-2), 153.76 (C-6). ESI MS m/z (%): 519.3 (100) [M + H], 563.4
(21) [M + H]; HRMS ESI (C26H31O2N8S) calculated: 519.22852; found:
519.22853.
(4-(2-(pyrazin-2-ylamino)-6-((4-[pyrrolidin-1-ylsulfonyl]phenyl)amino)-
9H-purin-9-yl)bicyclo[2.2.1]heptan-1-yl)methanol (26a): Aminopyrazine
(31 mg) was used in the second stage pf reaction, FCC in 2-15%
MeOH in CHCl3, yield 48 mg (44%) 1H NMR: δ 1.48-1.53 (m, 2H, H-
2a, H-6endo), 1.64-1.67 (m, 4H, NCH2CH2), 1.81-1.86 (m, 2H, H-2b,
H-6exo), 2.11 (bs, 2H, H-7), 2.13-2.19 (m, 2H, H-3a, H-5a), 2.26-2.31
(m, 2H, H-3b, H-5b), 3.12-3.15 (m, 4H, NCH2CH2), 3.53 (s, 2H, CH2O),
7.67-7.70 (m, 2H, H-3″), 8.15 (s, 1H, H-8′), 8.20 (d, 1H, J5”′,6‴= 2.5, H-
5‴), 8.35 (dd, 1H, J6”′,5‴= 2.5, J6”′,3‴= 1.5, H-6‴), 8.44-8.47 (m, 2H, H-
2″), 9.58 (d, 1H, J3”′,6‴= 1.5, H-3‴), 10.09 (s, 1H, 2′-NH), 10.30 (s, 1H,
6′-NH). 13C NMR: δ 24.86 (NCH2CH2), 31.51 (C-2, C-6), 34.56 (C-3,
C-5), 43.73 (C-7), 47.97 (NCH2CH2), 48.37 (C-1), 64.43 (CH2O), 65.42
(C-4), 117.02 (C-5′), 120.22 (C-2″), 128.21 (C-3″), 128.64 (C-4″),
135.66 (C-3‴), 137.02 (C-5‴), 139.50 (C-8′), 142.46 (C-6‴), 144.35
(C-1″), 150.49 and 151.25 (C-2‴, C-4′), 151.87 and 153.38 (C-2′, C-
6′). ESI MS m/z (%): 562.2 (13) [M + H], 584.2 (100) [M + H]; HRMS
ESI (C27H31O3N9S) calculated: 584.21628; found: 584.21624.
NMR:
δ 1.26-1.34 (m, 1H, H-4‴a), 1.38-1.50 (m, 2H, H-3‴a),
1.62-1.68 (m, 4H, NCH2CH2), 1.71-1.79 (m, 1H, H-4‴b), 1.86-1.93
(m, 2H, H-2‴a), 1.97-2.08 (m, 4H, H-2‴b, H-3‴b), 3.10-3.17 (m, 4H,
NCH2CH2), 4.27-4.37 (m, 1H, H-1‴), 6.91-6.97 (m, 1H, H-4″),
7.24-7.31 (m, 2H, H-3″), 7.66-7.72 (m, 2H, H-2′), 7.77-7.84 (m, 2H,
H-2″), 8.15 (s, 1H, H-8), 8.27-8.34 (m, 2H, H-3′), 9.24 (s, 1H, 2-NH).
10.16 (s, 1H, 6-NH). 13C NMR: δ 24.67 (NCH2CH2), 24.93 (C-4‴),
25.24 (C-3‴), 31.99 (C-2‴), 47.79 (NCH2CH2), 53.85 (C-1‴), 115.52
(C-5), 118.83 (C-2″), 119.87 (C-2′), 120.85 (C-4″), 127.99 (C-3′),
128.29 (C-4′), 128.32 (C-3″), 138.21 (C-8), 141.14 (C-1″), 144.32 (C-
1′), 150.99 (C-4), 151.41 (C-6), 155.21 (C-2).ESI MS m/z (%): 518.2
(100) [M + H], 540.2 (12) [M + Na]; HRMS ESI (C27H32O2N7S) calcu-
lated: 518.23327; found: 518.23326.
(4-(2-(Pyridin-3-ylamino)-6-((4-[pyrrolidin-1-ylsulfonyl]phenyl)amino)-
9-Cyclohexyl-N2-(pyrazin-2-yl)-N6-(4-[pyrrolidin-1-ylsulfonyl]phenyl)-
9H-purine-2,6-diamine (26b): Aminopyrazine (34 mg) was used in the
second stage pf reaction, FCC in 1-5% MeOH in CHCl3, yield 41 mg
(29%), 1H NMR: δ 1.23-1.36 (m, 1H, H-4‴a), 1.39-1.52 (m, 2H, H-3‴
a), 1.63-1.68 (m, 4H, NCH2CH2), 1.71-1.78 (m, 1H, H-4‴b), 1.84-1.93
(m, 2H, H-3‴b), 1.95-2.12 (m, 4H, H-2‴), 3.10-3.17 (m, 4H,
NCH2CH2), 4.33-4.43 (m, 1H, H-1‴), 7.66-7.72 (m, 2H, H-3′), 8.20 (d,
1H, J5”,6″ = 2.6, H-5″), 8.27 (s, 1H, H-8), 8.35 (dd, 1H, J6”,5″ = 2.6,
9H-purin-9-yl)bicyclo[2.2.1]heptan-1-yl)methanol
(25a):
3-aminopyridine (30 mg) was used in the second stage pf reaction,
FCC in 5-20% MeOH in CHCl3, yield 35 mg (25%). 1H NMR: δ 1.52
(m, 2H, H-2b, H-6endo), 1.66 (m, 4H, NCH2CH2), 1.85 (m, 2H, H-2a,
H-6exo), 2.20-2.05 (m, 4H, H-3exo, H-5exo, H-7), 2.31 (m, 2H, H-
3endo, H-5endo), 3.15 (m, 4H, NCH2CH2), 3.55 (s, 2H, CH2O), 7.74
(m, 2H, H-3″), 7.91 (dd, 1H, J5”′,4‴= 8.8, J5”′,6‴= 5.3, H-5‴), 8.18 (s,
1H, H-8′), 8.29 (m, 2H, H-2″), 8.47 (dd, 1H, J6”′,5‴= 5.4, J6”′,4‴= 1.1, H-
6‴), 8.65 (ddd, 1H, J4”′,5‴= 8.8, J4‴,2‴= 2.5, J4”′,6‴= 1.2, H-4‴), 9.34 (d,
J6”,3″ = 1.5, H-6″), 8.40-8.45 (m, 2H, H-2′), 9.59 (d, 1H, J3”,6″ = 1.5, H-
3″), 10.13 (s, 1H, 2-NH), 10.32 (s, 1H, 6-NH). 13C NMR: δ 24.67
(NCH2CH2), 24.90 (C-4‴), 25.20 (C-3‴), 31.99 (C-2‴), 47.79
(NCH2CH2), 54.12 (C-1‴), 116.16 (C-5), 120.14 (C-2′), 128.00 (C-3′),
128.48 (C-4′), 135.61 (C-3″), 136.81 (C-5″), 139.00 (C-8), 142.19 (C-
6″), 144.08 (C-1′), 150.32 and 150.43 (C-2″, C-4), 151.49 and 153.42
(C-2, C-6). ESI MS m/z (%): 520.5 (100) [M + H], 542.5 (27) [M + Na];
HRMS ESI (C25H30O2N9S) calculated: 520.22377; found: 520.22387.
(4-(2-([6-aminopyridin-3-yl]amino)-6-((4-[pyrrolidin-1-ylsulfonyl]phe-
1H, J2”′,4‴= 2.4, H-2‴), 10.16 (s, 1H, 2′-NH), 10.38 (s, 1H, 6′-NH). 13
C
NMR: δ 24.70 (NCH2CH2), 31.31 (C-2, C-6), 34.45 (C-3, C-5), 43.60
(C-7), 47.81 (NCH2CH2), 48.21 (C-1), 64.15 (CH2O), 65.27 (C-4),
117.03 (C-5′), 120.02 (C-2″), 126.49 (C-5‴), 128.14 (C-3″), 128.90
(C-4″), 131.61 (C-4‴), 131.86 (C-2‴), 134.43 (C-6‴), 139.59 (C-8′),
140.32 (C-3‴), 143.99 (C-1″), 150.87 (C-4′), 151.76 (C-2′), 153.48 (C-
6′).ESI MS m/z (%): 561.2 (100) [M + H]; HRMS ESI (C28H39O3N8S)
calculated: 561.23908; found: 561.23901.
nyl)amino)-9H-purin-9-yl)bicyclo[2.2.1]heptan-1-yl)methanol
(27a):
9-Cyclohexyl-N2-(pyridin-3-yl)-N6-(4-[pyrrolidin-1-ylsulfonyl]phenyl)-
9H-purine-2,6-diamine (24b): 3-aminopyridine (34 mg) was used in the
second stage pf reaction, FCC in 1-10% MeOH in CHCl3, yield 55 mg
(38%). 1H NMR: δ 1.28-1.37 (m, 1H, H-4‴b), 1.44-1.57 (m, 2H, H-3‴
b), 1.61-1.69 (m, 4H, NCH2CH2), 1.70-1.77 (m, 1H, H-4‴a), 1.85-2.01
(m, 4H, H-2‴b, H-3‴a), 2.02-2.11 (m, 2H, H-2‴a), 3.18-3.11 (m, 4H,
NCH2CH2), 4.37-4.46 (m, 1H, H-1‴), 7.72-7.77 (m, 2H, H-3′), 7.91
(dd, 1H, J5”,4″ = 8.7, J5”,6″ = 5.3, H-5″), 8.24-8.30 (m, 2H, H-2′), 8.31
(s, 1H, H-8), 8.47 (dd, 1H, J6”,5″ = 5.4, J6”,4″ = 1.1, H-6″), 8.62 (ddd,
1H, J4”,5″ = 8.7, J4”,2″ = 2.6, J4”,6″ = 1.2, H-4″), 9.49 (d, 1H, J2”,4″ = 2.5,
H-2″), 10.22 (bs, 1H, 2-NH), 10.40 (bs, 1H, 6-NH). 13C NMR: δ 24.70
(NCH2CH2), 24.88 (C-4‴), 25.10 (C-3‴), 32.52 (C-2‴), 47.81
(NCH2CH2), 53.90 (C-1‴), 116.39 (C-5), 120.09 (C-2′), 126.59 (C-5″),
128.15 (C-3′), 128.96 (C-4′), 131.37 (C-2″), 132.11 (C-4″), 134.22 (C-
2,5-diaminopyridine dihydrochloride (59 mg) was used in the second
stage pf reaction, ratio of regioisomers 8:1 (HPLC), FCC in 5-20%
MeOH in CHCl3, only one isomer isolated with yield 40 mg (23%). 1H
NMR: δ 1.44-1.54 (m, 2H, H-2b, H-6endo), 1.61-1.70 (m, 4H,
NCH2CH2), 1.80-1.90 (m, 2H, H-2a, H-6exo), 2.04-2.13 (m, 4H, H-
3exo, H-5exo, H-7), 2.23-2.34 (m, 2H, H-3endo, H-5endo), 3.10-3.16
(m, 4H, NCH2CH2), 3.54 (s, 2H, CH2O), 7.04 (d, 1H, J5”′,4‴= 9.4, H-
5‴), 7.67-7.75 (m, 2H, H-3″), 7.89 (bs, 2H, NH2), 8.07 (s, 1H, H-8′),
8.13 (dd, 1H, J4”′,5‴= 9.5, J4”′,2‴= 2.5, H-2‴), 8.25-8.35 (m, 2H, H-2″),
8.57 (s, 1H, H-2‴), 9.47 (s, 1H, 2′-NH), 10.57 (s, 1H, 6′-NH). 13C
NMR: δ 24.70 (NCH2CH2), 31.22 (C-2, C-6), 34.40 (C-3, C-5), 43.58
(C-7), 47.82 (NCH2CH2), 48.22 (C-1), 64.10 (CH2O), 65.16 (C-4),
113.53 (C-5‴), 116.36 (C-5′), 119.77 (C-2″), 128.09 (C-3″), 128.38
(C-4″), 128.51 (C-3‴), 138.01 (C-4‴), 138.81 (C-8′), 144.24 (C-1″),