A. Kamal et al. / Bioorg. Med. Chem. xxx (2014) xxx–xxx
7
thoxyphenyl)-5,6-dihydronaphtho[2,3-d][1,3]dioxole-6-carboxyl-
ate (11, 200 mg, 0.46 mmol) and o-phenylenediamine (48 mg,
101.2, 60.7, 56.3, 52.1, 48.9, 47.6. MS (ESI): m/z 593 [M+H]+. HRMS
(ESI) calcd for [M+H]+ 593.09228; found: 593.09193.
0.46 mmol) to affords 12a as off white solid 184 mg, in 76% yield.
25
Mp: 161–164 °C; [
a
]
276 32.07 (c 0.99 mg/mL, CHCl3). 1H
5.5.5. ((5R,6R)-Methyl 7-(6-methoxy-1H-benzo[d]imidazol-2-
yl)-5-(3,4,5-trimethoxyphenyl)-5,6-dihydronaphtho[2,3-
d][1,3]dioxole-6-carboxylate) (12e)
This compound 12e was prepared by method described in Sec-
tion 5.5 employing (5R,6R)-methyl 7-formyl-5-(3,4,5-trimethoxy-
phenyl)-5,6-dihydronaphtho[2,3-d][1,3]dioxole-6-carboxylate (11,
200 mg, 0.46 mmol) and 4-methoxy-1,2-phenylenediamine
D
NMR (300 MHz, CDCl3) d 7.51 (dd, J = 6.0, 3.1 Hz, 2H), 7.27 (s,
1H), 7.20 (dd, J = 6.0, 3.1 Hz, 2H), 6.83(s, 1H), 6.61 (s, 1H), 6.20 (s,
2H), 5.95 (d, J = 1.3 Hz, 1H), 5.94 (d, J = 1.3 Hz, 1H), 4.57 (d,
J = 4.3 Hz, 1H), 4.38 (d, J = 4.4 Hz, 1H), 3.87 (s, 3H), 3.79 (s, 6H),
3.48 (s, 3H). 13C NMR (75 MHz, CDCl3) d 172.2, 153.3, 150.9,
148.1, 146.3, 144.1, 139.3, 138.0, 137.2, 134.8, 129.1, 126.9,
122.9, 114.3, 109.8, 108.5, 106.5, 101.2, 61.0, 56.0, 51.9, 48.7,
48.1. MS (ESI): m/z 515 [M+H]+. HRMS (ESI) calcd for C29H27O7N2
[M+H]+ 515.18128; found: 515.18064.
(64 mg, 0.46 mmol) to affords 12e as off white solid 172 mg, in
26.6
67% yield. Mp: 249–251 °C; [
a]
31.84 20.96 (c 1.19 mg/mL,
D
CHCl3). 1H NMR (300 MHz, CDCl3) d 7.36 (d, J = 8.8 Hz, 1H), 7.29
(S, 1H), 7.23 (s, 1H), 6.96 (d, J = 8.7 Hz, 1H), 6.87 (s, 1H), 6.55 (s,
1H), 6.35 (s, 2H), 5.97 (d, J = 3.7 Hz, 2H), 4.68 (d, J = 3.9 Hz, 1H),
3.99 (d, J = 4.4 Hz, 1H), 3.80 (s, 3H), 3.76 (s, 3H), 3.73 (s, 6H), 3.44
(s, 3H). 13C NMR (75 MHz, CDCl3) d 173.0, 156.5, 154.1, 151.3,
148.2, 146.5, 139.3, 138.4, 137.5, 136.9, 134.9, 129.3, 126.6,
118.8, 112.2, 109.9, 108.6, 106.5, 101.2, 99.3, 60.7, 56.3, 55.9,
52.1, 48.9, 47.6. MS (ESI): m/z 545 [M+H]+; HRMS (ESI) calcd for
5.5.2. ((5R,6R)-Methyl 7-(6-fluoro-1H-benzo[d]imidazol-2-yl)-5-
(3,4,5-trimethoxyphenyl)-5,6-dihydronaphtho[2,3-
d][1,3]dioxole-6-carboxylate) (12b)
This compound 12b was prepared by method described in Sec-
tion 5.5 employing (5R,6R)-methyl 7-formyl-5-(3,4,5-trimethoxy-
phenyl)-5,6-dihydronaphtho[2,3-d][1,3]dioxole-6-carboxylate (11,
200 mg, 0.46 mmol) and 4-flouro-1,2-phenylenediamine (58 mg,
C30H29O8N2 [M+H]+ 545.19240; found: 545.19226.
0.46 mmol) to affords 12a as off white solid 176 mg, in 70% yield.
Mp: 245–248 °C; [
a
]
198 65.01 (c 0.87 mg/mL, CHCl3). 1H
25.1
D
5.5.6. ((5R,6R)-Methyl 7-(6-methyl-1H-benzo[d]imidazol-2-yl)-
5-(3,4,5-trimethoxyphenyl)-5,6-dihydronaphtho[2,3-
d][1,3]dioxole-6-carboxylate) (12f)
This compound 12f was prepared by method described in Sec-
tion 5.5 employing (5R,6R)-methyl 7-formyl-5-(3,4,5-trimethoxy-
phenyl)-5,6-dihydronaphtho[2,3-d][1,3]dioxole-6-carboxylate (11,
200 mg, 0.46 mmol) and 4-methyl-1,2-phenylenediamine (56 mg,
NMR (300 MHz, CDCl3) d 7.39–7.48 (m, 2H), 7.21 (s, 1H), 6.91–
7.02 (m, 2H), 6.61 (s, 1H), 6.29 (s, 2H), 5.99 (s, 2H), 4.60 (d,
J = 4.3 Hz, 1H), 4.00 (d, J = 4.4 Hz, 1H), 3.87 (s, 3H), 3.80 (s, 6H),
3.46 (s, 3H). 13C NMR (75 MHz, CDCl3) d 172.1, 157.9, 153.3,
151.7, 148.1, 146.9, 144.1, 141.2, 138.2, 137.6, 135.1, 128.8,
126.8, 119.1, 110.7, 109.5, 108.2, 107.8, 101.8, 101.4, 60.8, 56.3,
52.1, 47.9, 45.7. MS (ESI): m/z 533 [M+H]+. HRMS (ESI) calcd for
0.46 mmol) to affords 12f as off white solid 158 mg, in 64% yield.
26.6
C
29H26O7N2F [M+H]+ 533.17186; found: 533.17099.
Mp: 164–166 °C; [
a
]
D
14.22 83.26 (c 0.90 mg/mL, CHCl3). 1H
NMR (500 MHz, CDCl3) d 7.59 (d, J = 7.41 Hz, 1H), 7.46 (s, 1H),
6.99 (d, J = 7.3 Hz, 1H), 6.88 (s, 1H), 6.58 (s, 1H), 6.36 (s, 2H), 5.95
(d, J = 1.3 Hz, 1H), 5.94 (d, J = 1.3 Hz, 1H), 4.61 (d, J = 3.7 Hz, 1H),
4.25–4.21 (m, 1H), 3.89 (s, 3H), 3.85 (s, 6H), 3.49 (s, 3H), 2.36 (s,
3H). 13C NMR (75 MHz, CDCl3) d 173.6, 153.0, 151.0, 148.1, 146.9,
144.1, 139.4, 138.0, 137.3, 135.1, 128.8, 126.8, 121.9, 117.9,
114.1, 109.6, 108.2, 107.7, 101.3, 60.6, 52.8, 52.1, 47.6, 46.2, 21.6.
MS (ESI): m/z 529 [M+H]+. HRMS (ESI) calcd for C30H29O7N2
[M+H]+ 529.19693; found: 529.19517.
5.5.3. ((5R,6R)-Methyl 7-(6-chloro-1H-benzo[d]imidazol-2-yl)-
5-(3,4,5-trimethoxyphenyl)-5,6-dihydronaphtho[2,3-
d][1,3]dioxole-6-carboxylate) (12c)
This compound 12c was prepared by method described in Sec-
tion 5.5 employing (5R,6R)-methyl 7-formyl-5-(3,4,5-trimethoxy-
phenyl)-5,6-dihydronaphtho[2,3-d][1,3]dioxole-6-carboxylate (11,
200 mg, 0.46 mmol) and 4-chloro-1,2-phenylenediamine (65 mg,
0.46 mmol) to affords 12c as off white solid 170 mg, in 66% yield.
26.6
Mp: 165–169 °C; [
a]
116.73 35.64 (c 1.40 mg/mL, CHCl3).
D
1H NMR (300 MHz, CDCl3) d 7.89 (s, 1H), 7.48 (d, J = 7.1 Hz, 1H),
7.29 (d, J = 7.3 Hz, 2H), 6.91 (s, 1H), 6.76 (s, 1H), 6.28 (s, 2H), 5.95
(s, 2H), 4.69 (d, J = 4.3 Hz, 1H), 4.05 (d, J = 4.5 Hz, 1H), 3.80
(s, 3H), 3.76 (s, 6H), 3.48 (s, 3H). 13C NMR (75 MHz, CDCl3) d
172.8, 153.9, 151.6, 148.0, 146.4, 139.3, 138.6, 138.1, 137.3,
134.9, 129.2, 128.8, 126.6, 124.6, 118.1, 111.5, 109.8, 108.8,
106.7, 101.3, 60.9, 56.1, 52.2, 48.8, 47.9. MS (ESI): m/z 549
[M+H]+. HRMS (ESI) calcd for C29H26O7N2Cl [M+H]+ 549.14231;
found: 549.14188.
5.5.7. ((5R,6R)-Methyl 7-(6-(trifluoromethyl)-1H-
benzo[d]imidazol-2-yl)-5-(3,4,5-trimethoxyphenyl)-5,6-
dihydronaphtho[2,3-d][1,3]dioxole-6-carboxylate) (12g)
This compound 12g was prepared by method described in Sec-
tion 5.5 employing (5R,6R)-methyl 7-formyl-5-(3,4,5-trimethoxy-
phenyl)-5,6-dihydronaphtho[2,3-d][1,3]dioxole-6-carboxylate (11,
200 mg, 0.46 mmol) and 4-triflouromethyl-1,2-phenylenediamine
(81 mg, 0.46 mmol) to affords 12g as off white solid 164 mg, in
26.1
60% yield. Mp: 149–153 °C; [
a
]
D
95.06 39.89 (c 1.54 mg/mL,
CHCl3). 1H NMR (300 MHz, CDCl3) d 7.90 (d, J = 8.9 Hz, 1H), 7.78
(s, 1H), 7.36 (d, J = 8.8 Hz, 1H), 7.29 (s, 1H), 6.71 (s, 1H), 6.52 (s,
1H), 6.35 (s, 2H), 5.97 (d, J = 3.7 Hz, 2H), 4.68–4.73 (m, 1H), 3.97
(d, J = 4.4 Hz, 1H), 3.80 (s, 3H), 3.76 (s, 6H), 3.53 (s, 3H). 13C NMR
(75 MHz, CDCl3) d 173.0, 153.9, 151.8, 148.2, 146.4, 139.0, 137.7,
137.2, 135.1, 134.4, 129.2, 128.3, 126.5, 124.3, 119.6, 118.8,
112.3, 109.8, 108.7, 106.6, 101.1, 60.8, 56.2, 52.0, 48.4, 47.3. MS
(ESI): m/z 583 [M+H]+. HRMS (ESI) calcd for C30H26O7N2F3
[M+H]+ 583.16866; found: 583.16893.
5.5.4. ((5R,6R)-Methyl 7-(6-bromo-1H-benzo[d]imidazol-2-yl)-
5-(3,4,5-trimethoxyphenyl)-5,6-dihydronaphtho[2,3-
d][1,3]dioxole-6-carboxylate) (12d)
This compound 12d was prepared by method described in Sec-
tion 5.5 employing (5R,6R)-methyl 7-formyl-5-(3,4,5-trimethoxy-
phenyl)-5,6-dihydronaphtho[2,3-d][1,3]dioxole-6-carboxylate (11,
200 mg, 0.46 mmol) and 4-bromo-1,2-phenylenediamine (86 mg,
0.46 mmol) to affords 12d as off white solid 188 mg, in 67% yield.
26.6
Mp: 231–235 °C; [
a]
127.14 84.03 (c 0.78 mg/mL, CHCl3). 1H
D
NMR (500 MHz, CDCl3) d 7.79 (s, 1H), 7.46–7.51 (m, 1H), 7.43 (d,
J = 8.0 Hz, 1H), 7.20 (s, 1H), 6.91 (s, 1H), 6.62 (s, 1H), 6.27 (s, 2H),
6.05 (s, 2H), 4.61 (d, J = 4.7 Hz, 1H), 4.01–4.07 (m, 1H), 3.89 (s,
3H), 3.81 (s, 6H), 3.48 (s, 3H). 13C NMR (75 MHz, CDCl3) d 172.9,
154.0, 151.6, 148.1, 146.6, 139.9, 138.5, 137.9, 137.4, 135.0,
129.3, 126.6, 125.8, 119.1, 115.6, 112.3, 109.9, 108.6, 106.5,
5.5.8. ((5R,6R)-Methyl 7-(5,6-dimethyl-1H-benzo[d]imidazol-2-
yl)-5-(3,4,5-trimethoxyphenyl)-5,6-dihydronaphtho[2,3-
d][1,3]dioxole-6-carboxylate) (12h)
This compound 12h was prepared by method described in Sec-
tion 5.5 employing (5R,6R)-methyl 7-formyl-5-(3,4,5-trimethoxy-
phenyl)-5,6-dihydronaphtho[2,3-d][1,3]dioxole-6-carboxylate (11,