8.22 (m, 1H), 7.86-7.81 (m, 1H), 7.80 (d, 2H, J = 1,6 Hz), 7.69 (t,
1H, J = 1.6 Hz), 7.65-7.60 (m, 1H), 7.47 (t, 1H, J = 8 Hz), 3.52 (t,
2H, J = 6.8 Hz), 3.02 (t, 2H, J = 6.8 Hz), 1.98 (p, 2H, J = 6.8 Hz),
1.38 (s, 18H). 13CNMR (CD3OD): 169.2, 168.6, 151.1, 138.9,
134.5, 134.0, 128.7, 125.9, 124.4, 122.7, 121.5, 120.2, 40.0, 36.1,
34.5, 30.4, 27.5. HRMS-ESI: C25H36N3O2 [M+H]+ calcd:
410.2808, found: 410.2797; mp 273-275 C (decomp.).
Compounds A4, A7, A8, B11, B12, C15, C16, D19, D20, E23,
E24, and F26 were synthesized in similar manner (Scheme 1).
3,5-Di-tert-butyl-N-(4-((3-
guanidinopropyl)carbamoyl)phenyl)benzamide
hydrochloride
(A4). 1H NMR (CD3OD): 7.89 (d, 2H, J = 9.2 Hz), 7.85 (d, 2H, J
= 9.2 Hz), 7.79 (d, 2H, J = 1.6 Hz), 7.68 (t, 1H, J = 1.6 Hz), 3.47
(t, 2H, J = 6.8 Hz), 3.27 (t, 2H, J = 6.8 Hz), 1.90 (p, 2H, J = 6.8
Hz), 1.38 (s, 18H). 13C NMR (CD3OD): 168.6, 168.5, 157.3,
151.1, 142.0, 134.1, 129.3, 127.7, 125.9, 121.6, 120.2, 38.7, 36.6,
34.5, 30.4, 28.7. HRMS-ESI: C26H38N5O2 [M+H]+ calcd:
452.3026, found: 452.3020; mp 205-207 C (decomp.).
N-(2-((2-Aminoethyl)carbamoyl)phenyl)-3,5-di-tert-
1
butylbenzamide hydrochloride (E21). H NMR (CD3OD): 8.50
(dd, 1H, J = 8.4 Hz, J = 1.2 Hz), 7.86 (d, 2H, J = 1.6 Hz), 7.82
(dd, 1H, J = 8.4 Hz, J = 1.2 Hz), 7.71 (t, 1H, J = 1.6 Hz), 7.57
(ddd, 1H, J = 8.8 Hz, J = 8.4 Hz, J = 1.2 Hz), 7.23 (ddd, 1H, J =
8.8 Hz, J = 8.4 Hz, J = 1.2 Hz), 3.68 (t, 2H, J = 6 Hz), 3.17 (t,
2H, J = 6 Hz), 1.40 (s, 18H). 13C NMR (CD3OD): 170.8, 167.3,
151.4, 138.9, 134.0, 132.1, 127.78, 126.1, 123.3, 121.6, 121.3,
121.3, 39.5, 37.5, 34.6, 30.4. HRMS-ESI: C24H34N3O2 [M+H]+
calcd: 396.2651, found: 396.2637; mp 259-261 C (decomp.).
3,5-Di-tert-butyl-N-(4-((2-
guanidinoethyl)carbamoyl)benzyl)benzamide
hydrochloride
(A7). 1H NMR (CD3OD): 7.83 (d, 2H, J = 8 Hz), 7.74 (d, 2H, J =
1.6 Hz), 7.64 (t, 1H, J = 1.6 Hz), 7.46 (d, 2H, J = 8 Hz), 4.63 (s,
2H), 3.55 (t, 2H, J = 6 Hz), 3.41 (t, 2H, J = 6 Hz), 1.35 (s, 18H).
13C NMR (CD3OD): 169.6, 169.3, 157.5, 151.1, 143.4, 133.3,
132.4, 127.2, 127.1, 125.6, 121.2, 42.8, 40.6, 38.6, 34.5, 30.4.
HRMS-ESI: C26H38N5O2 [M+H]+ calcd: 452.3026, found:
452.3015; mp 155-157 C (decomp.).
3,5-Di-tert-butyl-N-(2-((3-
aminopropyl)carbamoyl)phenyl)benzamide hydrochloride (E22).
1H NMR (CD3OD): 8.59 (dd, 1H, J1 = 8.4 Hz, J2 = 1.2 Hz), 7.87
(d, 2H, J = 1.6 Hz) 7.78 (dd, 1H, J1 = 8.4 Hz, J2 = 1.2 Hz), 7.71 (t,
1H, J = 1.6 Hz), 7.56 (ddd, 1H, J1 = 8.4 Hz, J2 = 7.2 Hz, J3 = 1.2
Hz), 7.22 (ddd, 1H, J1 = 8.4 Hz, J2 = 7.2 Hz, J3 = 1.2 Hz), 3.53 (t,
2H, J = 6.8 Hz), 3.02 (t, 2H, J = 6.8 Hz), 1.99 (p, 2H, J = 6.8 Hz),
1.40 (s, 18H). 13CNMR (CD3OD): 170.2, 166.9, 151.5, 139.1,
134.0, 132.1, 127.6, 126.0, 123.2, 121.3, 121.1, 121.0, 37.2, 36.1,
34.6, 30.4, 27.4. HRMS-ESI: C25H36N3O2 [M+H]+ calcd:
410.2808, found: 410.2805; mp 268-270 C (decomp.).
3,5-Di-tert-butyl-N-(4-(2-((2-guanidinoethyl)amino)-2-
oxoethyl)phenyl)benzamide hydrochloride (A8). 1H NMR
(CD3OD): 7.78 (d, 2H, J = 1.6 Hz), 7.67 (t, 1H, J = 1.6 Hz), 7.64
(d, 2H, J = 8.4 Hz), 7.31 (d, 2H, J = 8.4 Hz), 3.54 (s, 2H), 3.36 (t,
2H, J = 6 Hz), 3.29 (t, 2H, J = 6 Hz), 1.38 (s, 18H). 13C NMR
(CD3OD): 173.6, 168.6, 157.4, 151.1, 137.4, 134.2, 131.5, 129.1,
125.7, 121.7, 121.5, 41.9, 40.6, 38.2, 34.5, 30.4. HRMS-ESI:
C26H38N5O2 [M+H]+ calcd: 452.3026, found: 452.3011; mp 258-
260 C (decomp.).
N-(2-Aminoethyl)-3-(3,5-di-tert-butylbenzamido)-2-naphthamide
1
hydrochloride (F25). H NMR (CD3OD): 8.86 (s, 1H), 8.39 (s,
1H), 7.95 (dd, 1H, J1 = 8 Hz, J2 = 0.4 Hz), 8.00 (d, 2H, J = 1.6
Hz), 7.88 (dd, 1H, J1 = 8 Hz, J2 = 0.4 Hz), 7.73 (t, 1H, J = 1.6
Hz), 7.61 (ddd, 1H, J1 = 8.4 Hz, J2 = 6.8 Hz, J3 = 0.8 Hz), 7.51
(ddd, 1H, J1 = 8.4 Hz, J2 = 6.8 Hz, J3 = 0.8 Hz), 3.75 (t, 2H, J = 6
Hz), 3.24 (t, 2H, J = 6 Hz), 1.42 (s, 18H). 13C NMR (CD3OD):
171.0, 167.5, 151.5, 135.1, 134.5, 134.0, 129.3, 128.9, 128.3,
128.2, 127.1, 126.1, 125.7, 122.6, 121.3, 118.6, 39.3, 37.1, 34.6,
30.4. HRMS-ESI: C28H36N3O2 [M+H]+ calcd: 446.2808, found:
446.2787; mp 285-287 C (decomp.).
3,5-Di-tert-butyl-N-(4-((2-guanidinoethyl)carbamoyl)phenyl)-N-
methylbenzamide hydrochloride (B11). H NMR (CD3OD): 7.76
1
(d, 2H, J = 8.8 Hz), 7.36 (t, 1H, J = 1.6 Hz), 7.22 (d, 2H, J = 8.8
Hz), 7.15 (d, 2H, J = 1.6 Hz), 3.51 (t, 2H, J = 6 Hz), 3.51 (s, 3H),
3.37 (t, 2H, J = 6 Hz), 1.16 (s, 18H). 13C NMR (CD3OD): 172.2,
168.2, 157.5, 150.4, 148.2, 134.4, 131.5, 128.0, 126.7, 123.5,
123.1, 40.6, 38.5, 37.0, 34.2, 30.2. HRMS-ESI: C26H38N5O2
[M+H]+ calcd: 452.3026, found: 452.3016; mp 149-151 C
(decomp.).
3,5-Di-tert-butyl-N-(4-((2-
guanidinoethyl)carbamoyl)phenyl)benzamide hydrochloride (A3)
was synthesized according to a modified method described
elsewhere.30 Briefly, N-(4-((2-aminoethyl)carbamoyl)phenyl)-
3,5-di-tert-butylbenzamide (198 mg, 0.5 mmol) was dissolved in
DMF (0.5 ml) and 1-amidino-1H-1,2,4-triazole hydrochloride
(74 mg, 0.5 mmol) was added to the reaction mixture. The
reaction vessel was sealed with a septum, and the reaction
mixture stirred for 18 h at room temperature. The reaction
mixture was filtered, Et2O (10 ml) was added to the liquid
filtrate, and the mixture was stirred for 1 h at room temperature.
The ether layer was decanted off, a new portion of Et2O (10 ml)
was added, and the mixture stirred for 10 h at room temperature.
Et2O was removed from the solid precipitate. Obtained 3,5-di-
tert-butyl-N-(4-((2-guanidinoethyl)carbamoyl)phenyl)benzamide
hydrochloride was purified by recrystallization from MeOH/Et2O
3,5-Di-tert-butyl-N-(4-((3-guanidinopropyl)carbamoyl)phenyl)-
N-methylbenzamide hydrochloride (B12). 1H NMR (CD3OD):
7.75 (d, 2H, J = 8.4 Hz), 7.36 (t, 1H, J = 1.6 Hz), 7.21 (d, 2H, J =
8.4 Hz), 7.15 (d, 2H, J = 1.6 Hz), 3.51 (s, 3H), 3.41 (t, 2H, J = 6.8
Hz), 3.21 (t, 2H, J = 6.8 Hz), 1.83 (p, 2H, J = 6.8 Hz), 1.16 (s,
18H). 13C NMR (CD3OD): 172.1, 167.7, 157.3, 150.4, 148.0,
134.4, 131.9, 127.9, 126.7, 123.5, 123.1, 38.6, 37.0, 36.5, 34.2,
30.2, 28.6. HRMS-ESI: C27H40N5O2 [M+H]+ calcd: 466.3182,
found: 466.3162; mp 139-141 C (decomp.).
N1-(3,5-di-tert-butylphenyl)-N4-(2-
guanidinoethyl)terephthalamide hydrochloride (C15). H NMR
1
(CD3OD): 8.03 (d, 2H, J = 8.8 Hz), 7.97 (d, 2H, J = 8.8 Hz), 7.59
(s, 2H), 7.28 (s, 1H), 3.60 (t, 2H, J = 6 Hz), 3.45 (t, 2H, J = 6
Hz), 1.34 (18s). 13C NMR (CD3OD): 168.6, 166.4, 157.5, 151.2,
138.1, 137.6, 136.4, 127.5, 127.2, 118.5, 115.5, 40.6, 38.7, 34.4,
30.4. HRMS-ESI: C25H36N5O2 [M+H]+ calcd: 438.2869, found:
438.2869; mp 305-307 C (decomp.).
1
in 91% yield (216 mg). H NMR (CD3OD): 7.89 (d, 2H, J = 9.2
Hz), 7.85 (d, 2H, J = 9.2 Hz), 7.79 (d, 2H, J = 1.6 Hz), 7.69 (t,
1H, J = 1.6 Hz), 3.57 (t, 2H, J = 6.4 Hz), 3.43 (t, 2H, J = 6.4 Hz),
1.38 (s, 18H). 13C NMR (CD3OD): 168.9, 168.6, 157.5, 151.1,
142.2, 134.1, 128.9, 127.8, 126.0, 121.6, 120.2, 40.7, 38.6, 34.5,
30.3. HRMS-ESI: C25H36N5O2 [M+H]+ calcd: 438.2869, found:
438.2855; mp 307-309 C (decomp.).
N1-(3,5-Di-tert-butylphenyl)-N4-(3-
guanidinopropyl)terephthalamide hydrochloride (C16). H NMR
1
(CD3OD): 8.02 (d, 2H, J = 8 Hz), 7.95 (d, 2H, J = 8 Hz), 7.59 (s,