A. L. LaFrate et al. / Bioorg. Med. Chem. 16 (2008) 10075–10084
10083
4.2.3. 1-Chloro-6-methoxy-3,4-dihydronaphthalene-2-carboxal-
4.2.10. 1-Phenoxy-3,4-dihydronaphthalene-2-carboxaldehyde
dehyde aminoguanylhydrazone HCl (19)
aminoguanylhydrazone HCl (26)
Following the general procedure for hydrazone formation, 19
was obtained as a white solid (105 mg, 33%). Mp 216 °C. 1H NMR
(500 MHz, methanol-d4) d: 2.61–2.80 (m, 4H) 3.72 (s, 3H) 6.65–
6.78 (m, 2H) 7.52 (d, J = 8.58 Hz, 1H) 8.39 (s, 1H). 13C NMR
(125 MHz, methanol-d4) d: 24.17, 28.52, 55.89, 112.84, 114.44,
126.48, 128.12, 128.46, 136.75, 141.26, 147.54, 156.83, 162.50.
HRMS: Calcd for C13H16N4OCl [M+H]+: 279.1013. Found:
279.1009.
Following the general procedure for hydrazone formation, 26
was obtained as an orange solid (224 mg, 66%). Mp 262–264 °C.
1H NMR (500 MHz, methanol-d4) d: 2.75 (t, J = 7.83 Hz, 2H) 2.87
(t, J = 7.93 Hz, 2H) 6.80–6.92 (m, 3H) 6.97 (t, J = 7.50 Hz, 1H)
7.05–7.22 (m, 5H) 8.12 (s, 1H). 13C NMR (125 MHz, methanol-d4)
d: 22.04, 28.26, 116.31, 123.34, 123.50, 124.61, 126.63, 127.60,
128.89, 130.51, 131.00, 131.21, 140.20, 145.83, 153.06, 159.54.
HRMS: Calcd for C18H19N4O [M+H]+: 307.1559. Found: 307.1563.
4.2.4. 1-Chloro-5,7-dimethyl-3,4-dihydronaphthalene-2-
carboxaldehyde aminoguanylhydrazone HCl (20)
4.2.11. 1-(1,1,1,-Trifluoromethyl)-3,4-dihydronaphthalene-2-
carboxaldehyde aminoguanylhydrazone HCl (27)
Following the general procedure for hydrazone formation, 20
was obtained as a white solid (176 mg, 56%). Mp decomposed at
242 °C. 1H NMR (500 MHz, methanol-d4) d: 2.17 (d, J = 13.72 Hz,
3H) 2.19 (s, 3H) 2.66 (s, 4H) 6.91 (s, 1H) 7.29 (s, 1H) 8.41 (s, 1H).
13C NMR (125 MHz, methanol-d4) d: 19.45, 21.13, 23.79, 24.01,
49.85, 125.03, 130.42, 133.29, 133.61, 134.43, 136.07, 136.82,
147.51, 152.39. HRMS: Calcd for C14H18N4Cl [M+H]+: 277.1220.
Found: 277.1207.
Following the general procedure for hydrazone formation, 27
was obtained as a white solid (55 mg, 81%). Mp decomposed at
230 °C. 1H NMR (400 MHz, methanol-d4) d: 2.69–2.78 (m, 2H)
2.78–2.87 (m, 2H) 7.20–7.29 (m, 3H) 7.36–7.45 (m, 1H) 8.42–
8.47 (m, 1H). 13C NMR (125 MHz, methanol-d4) d: 24.45, 28.35,
124.38, 126.51, 126.55, 127.12, 127.86, 127.90, 128.88, 130.34,
139.22, 145.95, 145.96. HRMS: Calcd for C13H15N4F3 [M+H]+:
283.1171. Found: 283.1166.
4.2.5. 1-Chloro-3-dihydro-4-methylnaphthalene-2-
carboxaldehyde aminoguanylhydrazone HCl (21)
4.2.12. b-Chlorocinnamaldehyde aminoguanylhydrazone HCl
(28)
Following the general procedure for hydrazone formation, the
product did not precipitate upon HCl addition. The crude free base
was used for CBI testing, no yield recorded. 1H NMR (500 MHz,
methanol-d4) d: 1.19 (s, 3H) 2.68–2.88 (m, 2H) 2.87–3.00 (m, 1H)
7.08–7.33 (m, 3H) 7.57–7.73 (m, 1H) 8.47 (s, 1H).
Following the general procedure for hydrazone formation, 28
was obtained as a white powder (210 mg, 81%). Mp 182–184 °C.
1H NMR (500 MHz, methanol-d4) d: 7.08 (d, J = 8.79 Hz, 1H) 7.45
(d, J = 3.00 Hz, 3H) 7.73–7.80 (m, 2H) 8.32 (d, J = 9.00 Hz, 1H). 13C
NMR (125 MHz, methanol-d4) d: 147.2, 142.0, 137.6, 131.4, 129.8,
127.6, 122.5. ESI-MS: [M+H]+: 223.1.
4.2.6. 1-Chloro-3-dihydrobenzocyclopentene-2-carboxal-
dehyde (22)
4.2.13. b-Chloro-a-methylcinnamaldehyde aminoguanyl-
Following the general procedure for hydrazone formation, 22
was obtained as a white powder (96 mg, 63%). Mp 206–210 °C.
1H NMR (500 MHz, methanol-d4) d: 8.27 (s, 1H), 7.49 (m, 2H),
7.37 (m, 2H), 3.78 (m, 2H). ESI-MS: C11H12ClN4 [M+H]+: 235.1.
hydrazone HCl (29)
Following the general procedure for hydrazone formation, 29
was obtained as a white solid (183 mg, 67%). Note: began with a
6:1 mixture of E to Z isomers, and only one isomer was obtained
for the guanylhydrazone. Mp 220–222 °C. 1H NMR (500 MHz,
methanol-d4) d: 2.25 (s, 3H) 7.37 (d, J = 7.72 Hz, 2H) 7.41–7.50
(m, 3H) 7.75 (s, 1H). 13C NMR (125 MHz, methanol-d4) d: 157.0,
148.6, 142.3, 138.6, 132.4, 131.0, 130.1, 15.2. ESI-MS: [M+H]+:
237.1.
4.2.7. 9-Chloro-6,7-dihydro-5-benzocycloheptene-8-
carboxaldehyde aminoguanylhydrazone HCl (23)
Following the general procedure for hydrazone formation, 23
was obtained as a white powder (176 mg, 59%). Mp 214–216 °C.
1H NMR (500 MHz, methanol-d4) d: 8.55 (s, 1H), 7.58 (m, 2H),
7.33 (m, 2H), 2.64 (t, J = 7.08 Hz, 2H), 2.46 (t, J = 6.96 Hz, 2H),
2.19 (t, 7.08 Hz, 2H). 13C NMR (125 MHz, methanol-d4) d: 157.1,
147.1, 141.6, 136.5, 134.2, 131.1, 130.6, 129.7, 129.1, 127.5, 34.4,
25.0. ESI-MS: [M+H]+: 263.1.
4.2.14. 3-Chloro-3-naphthalen-1-yl-propenal aminoguanyl-
hydrazone HCl (30)
Following the general procedure for hydrazone formation, 30
was obtained as a white powder (96 mg, 63%). Mp 190–192 °C.
1H NMR (500 MHz, methanol-d4) d: 6.85 (d, J = 9.86 Hz, 1H) 7.23
(d, J = 9.00 Hz, 1H) 7.51–7.67 (m, 2H) 7.77–8.03 (m, 3H) 8.30 (s,
1H). ESI-MS: C14H13N4Cl [M+H]+: 273.
4.2.8. 1-Bromo-3,4-dihydronaphthalene-2-carboxaldehyde
aminoguanylhydrazone HCl (24)
Following the general procedure for hydrazone formation, 24
was obtained as a white solid (170 mg, 52%). Mp 230–232 °C. 1H
NMR (500 MHz, methanol-d4) d: 2.71–2.90 (m, 4H) 7.12–7.21 (m,
1H) 7.24 (dd, J = 5.36, 3.43 Hz, 2H) 7.62–7.76 (m, 1H) 8.49 (s,
1H). 13C NMR (125 MHz, methanol-d4) d: 25.30, 28.18, 127.90,
127.93, 128.35, 128.76, 129.81, 130.79, 134.08, 134.59, 139.23,
149.93. HRMS: Calcd for C12H14N4Br [M+H]+: 293.0402. Found:
293.0393.
4.2.15. 2-(1-Naphthalenylmethylene) hydrazinecarboxi-
midamide HCl (31)
Followingthegeneralprocedureforhydrazoneformation, 31was
obtained as a white solid (241 mg, 97%). Mp 162 °C. 1H NMR
(500 MHz, methanol-d4) d: 8.87 (s, 1H), 8.42 (d, J = 8.36 Hz, 1H),
8.09 (d, J = 7.08 Hz, 1H), 7.94 (d, J = 8.15 Hz, 1H), 7.89 (d,
J = 8.15 Hz, 1H), 7.58 (m, 1H), 7.51 (t, J = 7.72 Hz, 2H). 13C NMR
(125 MHz, methanol-d4) d: 157.3, 148.4, 135.5, 132.7, 132.5, 130.2,
130.1, 128.6, 128.2, 127.5, 126.6, 124.3. ESI-MS: [M+H]+: 213.2.
4.2.9. 1-Methoxy-3,4-dihydronaphthalene-2-carboxaldehyde
aminoguanylhydrazone HCl (25)
4.2.16. 2-(2-Naphthalenylmethylene)hydrazine-
carboximidamideHCl (32)
Following the general procedure for hydrazone formation, 32
was obtained as a white solid (216 mg, 87%). Mp 260–262 °C. 1H
NMR (500 MHz, methanol-d4) d: 8.34 (s, 1H), 8.20 (m, 1H), 8.19
(2, 1H), 7.94 (m, 2H), 7.55 (m, 2H). 13C NMR (125 MHz, metha-
Following the general procedure for hydrazone formation, the
product did not precipitate upon HCl addition. The crude free base
was used for CBI testing, no yield recorded. 1H NMR (500 MHz,
methanol-d4) d: 2.58–2.83 (m, 4H) 3.67 (s, 3H) 7.08–7.25 (m, 3H)
7.31–7.40 (m, 1H) 8.29 (s, 1H).