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6.11.19. 40-Chloro-N-[6-[(methylanilino)methyl]-7,8-dihydro-2-
naphthalenyl][1,10-biphenyl]-4-carboxamide (2e)
diluted with EtOAc and the solution was washed with 10% K2CO3
and brine, dried over Na2SO4. The solution was passed through
NH silica gel (eluted with EtOAc) and concentrated in vacuo. The
oil was purified by silica gel column chromatography eluting 25%
- 50% EtOAc in hexane to give 14 (6.44 g, 85%) as a solid, which
was collected and washed with i-Pr2O. 1H NMR (CDCl3) d: 1.48
(9H, s), 2.20 (2H, t, J = 8.1 Hz), 2.80–2.85 (5H, m), 3.96 (2H, s),
6.24 (1H, s), 6.99 (1H, d, J = 7.8 Hz), 7.33 (1H, d, J = 9.0 Hz), 7.46
(1H, s), 7.61 (2H, d, J= 8.7 Hz), 7.72 (2H, d, J = 8.7 Hz), 7.80 (1H, s).
The following compound (2k) was prepared in the same man-
ner as described for 1d.
Yield 20%, yellow crystals, mp 177–179 °C (THF–hexane). 1H
NMR (CDCl 3)
(2H, m), 2.84–2.90 (2H, m), 3.00 (3H, s),
d: 2.23–2.28
4.00 (2H, s), 6.29 (1H, s), 6.68–6.76 (3H, m), 6.97 (1H, d,
J = 8.4 Hz), 7.20–7.25 (2H, m), 7.30–7.33 (1H, m), 7.43 (2H, m),
7.53–7.57 (3H, m), 7.66 (2H, d, J = 8.4 Hz), 7.76 (1H, s), 7.93 (2H,
d, J = 8.4 Hz). Anal. Calcd for C31H27ClN2O: C, 77.73; H, 5.68; N,
5.85. Found: C, 77.45; H, 5.57; N, 6.04.
6.11.20. 40-Chloro-N-[6-(4-morpholinylmethyl)-7,8-dihydro-2-
naphthalenyl][1,10-biphenyl]-4-carboxamide (2f)
Yield 30%, yellow crystals, mp 194–196 °C (THF–hexane). 1H
NMR (CDCl3) d: 2.34 (2H, t, J = 7.8 Hz), 2.45 (4H, m), 2.84 (2H, t,
J = 7.8 Hz), 3.06 (2H, s), 3.73 (4H, m), 6.36 (1H, s), 7.02 (1H, d,
J = 8.1 Hz), 7.36–7.57 (6H, m), 7.67 (2H, d, J = 8.4 Hz), 7.80 (1H, s),
7.94 (2H, d, J = 8.4 Hz). Anal. Calcd for C28H27ClN2O2: C, 73.27; H,
5.93; N, 6.10. Found: C, 73.30; H, 5.93; N, 5.98.
6.11.26. tert-Butyl (6-(40-chlorobiphenyl-4-ylcarboxamido)-3,4-
dihydronaphthalen-2-yl)methyl(methyl) carbamate (2k)
Yield 69%, white crystals, mp 191–193 °C (i-Pr2O). 1H NMR
(CDCl3) d: 1.48 (9H, s), 2.22 (2H, m), 2.82–2.88 (5H, m), 3.96 (2H,
m), 6.25 (1H, s), 7.01 (1H, d, J = 8.1 Hz), 7.38 (1H, d, J = 8.4 Hz),
7.42–7.46 (2H, m), 7.51–7.57 (3H, m), 7.66 (2H, d, J = 8.4 Hz),
7.80 (1H, s), 7.93 (2H, d, J = 8.7 Hz). Anal. Calcd for C30H31ClN2O3:
C, 71.63; H, 6.21; N, 5.57. Found: C, 71.65; H, 6.25; N, 5.52.
6.11.21. 40-Chloro-N-[6-(1-pyrrolidinylmethyl)-7,8-dihydro-2-
naphthalenyl][1,10-biphenyl]-4-carboxamide (2g)
Yield 40%, white crystals, mp 185–187 °C (THF–hexane). 1H
NMR (CDCl3) d: 1.83 (4H, m), 2.35 (2H, t, J = 8.1 Hz), 2.52 (4H, m),
2.84 (2H, t, J = 8.1 Hz), 3.18 (2H, s), 6.36 (1H, s), 7.02 (1H, d,
J = 8.4 Hz), 7.39–7.56 (6H, m), 7.66 (2H, d, J = 7.5 Hz), 7.82 (1H, s),
7.93 (2H, d, J = 7.5 Hz). Anal. Calcd for C28H27ClN2Oꢁ0.2H2O: C,
75.31; H, 6.18; N, 6.27. Found: C, 75.14; H, 5.99; N, 6.35.
6.11.27. 40-Chloro-N-[6-(methylamino)methyl]-7,8-dihydro-2-
naphthalenyl][1,10-biphenyl]-4-carboxamide 2,2,2-
trifluoroacetate (2j)
A solution of 2k (4.72 g, 9.38 mmol) in TFA (50 mL, 9.38 mmol)
was stirred for 30 min and concentrated in vacuo. The residue was
solidified with EtOAc and washed with same solvent to afford 2j
(4.70 g, 97%) as a light gray solid. Mp >210 °C (EtOAc, decomposi-
tion). 1H NMR (DMSO-d6) d: 2.29–2.34 (2H, t, J = 8.1 Hz), 2.59
(3H, s), 2.79–2.93 (2H, t, J = 8.1 Hz), 3.70 (2H, s), 6.58 (1H, s), 7.10
(1H, d, J = 8.4 Hz), 7.54–7.66 (4H, m), 7.78–7.85 (4H, m), 8.05
(2H, d, J = 8.4 Hz), 8.69 (2H, br s), 10.30 (1H, s). Anal. Calcd for
6.11.22. 40-Chloro-N-[6-(1-piperidinylmethyl)-7,8-dihydro-2-
naphthalenyl][1,10-biphenyl]-4-carboxamide (2h)
Yield 43%, white crystals, mp 209–211 °C (THF–hexane). 1H
NMR (CDCl3) d: 1.26–1.61 (6H, m), 2.30–2.36 (6H, m), 2.83 (2H, t,
J = 8.4 Hz), 3.02 (2H, s), 6.33 (1H, s), 7.01 (1H, d, J = 8.1 Hz), 7.36–
7.49 (4H, m), 7.55 (2H, d, J = 8.4 Hz), 7.66 (2H, d, J = 8.4 Hz), 7.81
(1H, s), 7.93 (2H, d, J = 8.1 Hz). Anal. Calcd for C29H29ClN2Oꢁ1.5H2O:
C, 71.96; H, 6.66; N, 5.79. Found: C, 71.42; H, 6.14; N, 5.64.
C27H24ClF3N2O3: C, 62.73; H, 4.68; N, 5.42; Cl, 6.86; F, 11.03. Found:
C, 62.51; H, 4.75; N, 5.27.
6.11.28. 40-Chloro-N-(6-((N-methylacetamido)methyl)-7,8-
dihydronaphthalen-2-yl)biphenyl-4-carboxamide (2l)
To a solution of 2j (200 mg, 0.39 mmol) in pyridine (2 mL) was
added acetic anhydride (0.073 mL, 0.77 mmol) at room tempera-
ture. The reaction mixture was stirred for 2 h and product was
crystallized. H2O was added to the mixture and the precipitates
were washed with CH3CN and i-Pr2O to afford 2l (135 mg, 78%)
as a white powder. Mp 233–235 °C (pyridine–H2O). 1H NMR
(DMSO-d6) d: 2.02–2.19 (5H, m), 2.73–2.93 (5H, m), 4.05 (2H, s),
6.20, 6.27 (1H, sx2), 7.02–7.07 (1H, m), 7.54–7.62 (4H, m), 7.78–
7.85 (4H, m), 8.05 (2H, d, J = 8.4 Hz), 10.22, 10.23 (1H, sx2). Anal.
Calcd for C27H25ClN2O2: C, 72.88; H, 5.66; N, 6.30; Cl, 7.97. Found:
C, 72.84; H, 5.71; N, 6.35.
6.11.23. 40-Chloro-N-[6-[(4-methyl-1-piperazinyl)methyl]-7,8-
dihydro-2-naphthalenyl][1,10-biphenyl]-4-carboxamide (2i)
Yield 21%, yellow crystals, mp 220–222 °C (THF–hexane). 1H
NMR (CDCl3) d: 2.30 (3H, s), 2.25–2.50 (10H, m), 2.83 (2H, t,
J = 8.1 Hz), 3.07 (2H, s), 6.35 (1H, s), 7.01 (1H, d, J = 8.1 Hz), 7.36
(1H, d, J = 7.8 Hz), 7.44 (2H, d, J = 8.4 Hz), 7.51 (1H, s), 7.55 (2H,
d, J = 8.4 Hz), 7.66 (2H, d, J = 8.4 Hz), 7.84 (1H, s), 7.93 (2H, d,
J = 8.4 Hz). Anal. Calcd for C29H30ClN3O: C, 73.79; H, 6.41; N, 8.90.
Found: C, 73.73; H, 6.45; N, 8.72.
6.11.24. tert-Butyl (6-amino-3,4-dihydronaphthalen-2-
yl)methyl(methyl)carbamate (6d)
The following compounds (2m–o) was prepared in the same
manner as described for 2l.
Di-tert-butyl dicarbonate (4.22 mL, 18.4 mmol) in CH3CN
(100 mL) was added dropwise to
a solution of 6b (3.46 g,
18.4 mmol) and triethylamine (2.56 mL, 18.4 mmol) in CH3CN
(50 mL) at 0 °C for 1 h. The reaction mixture was stirred for 3 h
at same temperature and concentrated in vacuo and the oil was
purified by silica gel column chromatography eluting 25% - 50%
EtOAc in hexane to give 6d (4.62 g, 87%) as a light yellow oil. 1H
NMR (CDCl3) d: 1.47 (9H, s), 2.15 (2H, t, J = 8.1 Hz), 2.73 (2H, t,
J = 8.1 Hz), 2.82 (3H, br s), 3.61 (2H, s), 4.08 (2H, br s), 6.17 (1H,
s), 6.46–6.48 (2H, m), 6.82 (1H, d, J = 8.7 Hz).
6.11.29. 40-Chloro-N-(6-((N-methylpropionamido)methyl)-7,8-
dihydronaphthalen-2-yl)biphenyl-4-carboxamide (2m)
Yield 80%, white crystals, mp 220–222 °C (EtOAc). 1H NMR
(DMSO-d6) d: 0.97–1.05 (3H, m), 2.07–2.18 (2H, m), 2.29–2.43
(2H, m), 2.73–2.82 (2H, m), 2.84, 2.92 (3H, sx2), 4.06 (2H, s),
6.18, 6.26 (1H, sx2), 7.01–7.06 (1H, m), 7.54–7.62 (4H, m), 7.78–
7.85 (4H, m), 8.05 (2H, d, J = 8.4 Hz), 10.22 (1H, s). Anal. Calcd for
C28H27ClN2O2ꢁ0.1H2O: C, 72.98; H, 5.95; N, 6.08; Cl, 7.72. Found:
C, 72.83; H, 5.96; N, 6.13.
6.11.25. tert-Butyl (6-(4-bromobenzamido)-3,4-
dihydronaphthalen-2-yl)methyl(methyl)carbamate (14)
4-Bromobenzoyl chloride (3.51 g, 16.0 mmol) was added drop-
wise to a solution of 6d (4.61 g, 16.0 mmol) and TEA (4.45 mL,
32.0 mmol) in THF (70 mL) at 0 °C for 1 h and the reaction mixture
was stirred for 2 h at same temperature. The reaction mixture was
6.11.30. Ethyl (6-(40-chlorobiphenyl-4-ylcarboxamido)-3,4-
dihydronaphthalen-2-yl)methyl(methyl) carbamate (2n)
Yield 79%, white crystals, mp 181–182 °C (EtOAc–i-Pr2O). 1H
NMR (DMSO-d6) d: 1.20 (3H, m), 2.11–2.16 (2H, m), 2.75–2.82
(5H, m), 3.98 (2H, s), 4.07 (2H, q, J = 6.9 Hz), 6.27 (1H, s), 7.04