112 mL) were added. The reaction mixture was heated at 80 °C
for 2–3 h under nitrogen atmosphere with a mechanical stirrer.
After reaching rt, the mixture was filtered and the pH of the sol-
ution was adjusted to 8 by the addition of 1 M NaOH. The
resulting aqueous phase was extracted with CH2Cl2 (3 ×
150 ml). The combined organic phases were dried (MgSO4) and
evaporated in vacuo to give 19.6 g (63% yield from 14) of a
white solid, compound 15: mp 93.7–94.0 °C; Anal. calc. for
C7H7BrINO: C, 25.64; H, 2.15; N, 4.27. Found: C, 25.39; H,
2.44; N, 4.09; δH (400 MHz, CDCl3) 7.16 (1H, s, ArH), 6.99
(1H, s, ArH), 3.84 (2H, br s, NH), 3.82 (3H, s, OMe);
δC (100 MHz, CDCl3) 148.12, 140.85, 121.49, 117.83, 111.84,
80.95, 56.09. ESI-MS m/z (%) 329.9 (100), 327.9 (100)
[M + 1]+.
N-Boc-5-bromo-2-iodo-4-methoxyaniline (16). Di-tert-butyl
dicarbonate (16.6 g, 0.0761 mol) and compound 15 (12.5 g,
0.0381 mol) were dissolved in ether (dry, 75 mL). The reaction
mixture was stirred for 7 days at 40 °C. The ether was removed
in vacuo, water (200 ml) was added and the resulting phase was
extracted with CH2Cl2 (3 × 100 mL). The combined organic
phases were dried (MgSO4) and evaporated in vacuo. The crude
product was purified by chromatography (PE : CH2Cl2 5 : 1) to
afford 15.0 g (92% yield) of 16 as a pale solid: mp
124.0–124.4°C; Anal. calc. for C12H15BrINO3: C, 33.67; H,
3.53; Br, 18.67; I, 29.65; N, 3.27. Found: C, 33.73; H, 3.48; N,
3.22; δH (400 MHz, CDCl3) 8.22 (1H, br s, CONH), 7.23 (1H,
s, ArH), 6.56 (1H, bs, ArH), 3.86 (3H, s, OMe), 1.54 (9H, s,
3Me); δC (100 MHz, CDCl3) 152.59, 152.27, 133.25, 125.05,
121.36, 87.42, 81.19, 56.68, 28.26; IR (neat) ν 3391, 3113,
1719, 1565, 1510, 1352, 1153, 1020 cm−1; HRMS(FAB+) m/z
calcd 427.9330, found 427.9332 [M + 1]+.
7-Bromo-6-methoxy-3,4-dipentylquinolin-2(1H)-one (17). Com-
pound 16 (500 mg, 1.17 mmol), Bn4NCl (325 mg, 1.17 mmol)
and Pd(OAc)2 (27 mg, 10 mol%) were charged in a dry flask
under nitrogen and 6-dodecyne (583 mg, 3.50 mmol), pyridine
(185 mg, 2.33 mmol) and dry DMF (Aldrich, 25 mL) were
added. The atmosphere was changed to CO (balloon). After 4 h
at 100 °C all of 22 was consumed. After cooling to rt, the reac-
tion mixture was diluted with EtOAc and the solvents were
removed in vacuo. 1 M ethanolic sodium hydroxide (50 mL)
was added and the mixture was left for 1 h at rt under stirring.
Then NH4Cl (aq, sat) was added and the solution was extracted
with EtOAc and water 3 times each. The combined organic
phases were evaporated. The crude product was purified by
chromatography (PE : EtOAc 4 : 1) to afford 299 mg (65% yield)
of 17 as a pale white solid: mp 141.0–143.0 °C; Anal. calc. for
C20H28BrNO2: C, 60.91; H, 7.16; N, 3.55. Found: C, 61.04; H,
6.57; N, 3.20; δH (400 MHz, CDCl3) 11.44 (1H, br s, CONH),
7.55 (1H, s, ArH), 7.08 (1H, s, ArH), 3.94 (3H, s, OMe), 2.85
(2H, t, J = 8.0 Hz, CH2), 2.73 (2H, t, J = 8.0 Hz, CH2),
1.66–1.36 (12H, m, CH2), 0.97 (6H, m, CH3); δC (100 MHz,
CDCl3) 163.18, 151.24, 146.52, 132.26, 132.12, 120.50, 120.00,
114.41, 106.05, 56.64, 32.26, 32.16, 29.29, 29.02, 28.97, 27.15,
22.56, 22.42, 14.08, 14.01; IR (neat) ν 2951, 2922, 2859, 1651,
1453, 1397, 1355, 1221, 1054 cm−1; HRMS(FAB+) m/z calcd
394.1329, found 394.1382 [M + 1]+.
dioxaborolan-2-yl) benzaldehyde12 (5.51 g, 18.1 mmol) and
Na2CO3 (3.06 g, 28.9 mmol) were charged into a round-bottom
flask equipped with a stirring bar. Then Pd(PPh3)4 (1.69 g,
1.45 mmol) was added under nitrogen. A mixture of degassed
dioxane (360 mL) and water (50 mL) was added to the solution
and the mixture was heated to 100 °C. The reaction was followed
by TLC and the starting material was consumed after 4–5 h at
which time the reaction was cooled to rt. The reaction mixture
was extracted with CH2Cl2 (3 × 100 mL). The combined organic
phases were dried (MgSO4) and purified by chromatography
(PE : EtOAc 2.5 : 1) to afford 7.00 g (98% yield) of 18 as a
white solid: mp 165.5–166.0 °C; Anal. calc. for C31H41NO4: C,
75.73; H, 8.41; N, 2.85. Found: C, 75.68; H, 8.31; N, 2.83; δH
(400 MHz, CDCl3) 11.89 (1H, s, CHO), 11.32 (1H, br s,
CONH), 9.96 (1H, s, ArH), 7.79 (1H, d, J = 2.1 Hz, ArH), 7.68
(1H, d, J = 2.1 Hz, ArH), 7.28 (1H, s, ArH), 7.20 (1H, s, ArH),
3.89 (3H, s, OMe), 2.92 (2H, t, J = 7.8 Hz, CH2), 2.76 (2H, t, J
= 7.8 Hz, CH2),1.76–1.31 (21H, m, CH2), 0.97 (3H, d, J = 7.2
Hz, Me), 0.87 (3H, d, J = 7.2 Hz, Me); δC (100 MHz, CDCl3)
197.22, 163.37, 160.78, 152.13, 146.82, 138.03, 135.65, 132.78,
132.15, 131.97, 131.65, 128.29, 120.45, 120.00, 117.59, 105.55,
35.00, 32.33, 32.20, 29.39, 29.30, 29.14, 29.03, 27.11, 22.54,
22.46, 18.44, 14.01, 13.97; IR (neat) ν 2958, 2921, 2871, 1643,
1359, 1216, 776, 622 cm−1; HRMS(FAB+) m/z calcd 492.3106,
found 492.3114 [M + 1]+.
3-tert-Butyl-2-hydroxy-5(6-hydroxy-2-oxo-3,4-dipentyl-1,2-dihy-
droquinolin-7-yl)benzaldehyde (19). To a solution of compound
18 (3.50 g, 7.12 mmol) in dry CH2Cl2 (150 mL) at −20 °C, was
added BBr3 (21.35 mL, 1 M in CH2Cl2). The mixture was left
stirring at rt and the reaction was followed by TLC. When all the
starting material was consumed, the reaction was quenched with
water (100 mL) and the solution was extracted with CH2Cl2
three times. The organic phases were collected and the solvent
was evaporated in vacuo resulting in brownish crystals. The
product was crystallized twice from EtOH to afford 2.79 g (82%
yield) of 19 as bright yellow crystals: mp 219.8–220.3 °C; Anal.
calc. for C30H39NO4: C, 75.44; H, 8.23; N, 2.93. Found: C,
75.07; H, 7.91; N, 2.69; δH (400 MHz, CDCl3) 11.93 (1H, br s,
ArOH), 11.63 (1H, br s, CONH), 9.90 (1H, s, CHO), 7.72 (1H,
d, J = 2.1 Hz, ArH), 7.62 (1H, d, J = 2.1 Hz, ArH), 7.28 (1H, s,
ArH), 7.21 (1H, s, ArH), 5.32 (1H, br, s, ArOH), 2.84 (2H, t, J
= 7.8, CH2), 2.72 (2H, t, J = 7.8, CH2), 1.63–1.25 (21H, m CH2
CH3), 0.97 (3H, d, J = 7.2 Hz, Me), 0.87 (3H, d, J = 7.2 Hz,
Me); δC (100 MHz, CDCl3) 197.02, 163.29, 161.12, 148.32,
147.09, 139.31, 135.05, 132.39, 131.56, 130.23, 127.22, 120.83,
120.67, 117.15, 109.95, 35.10, 32.35, 32.18, 29.58, 29.20,
29.10, 27.10, 22.53, 22.51, 14.03, 13.98; IR (neat) ν 31200,
2958, 2922, 2871, 1643, 1546, 1358, 1270, 1216, 1159 cm−1
;
HRMS(FAB+) m/z calcd 478.2932, found 478.2957 [M + 1]+.
N,N′-Bis[3-tert-butyl-(6,6′-dihydroxy-3,4-dipentyl-2-oxo-1,2-dihy-
droquinolin-7yl)salicylidene]-(1R,2R)-diphenyl-1,2-diaminoethane
(20). A solution of salicylaldehyde 19 (1.00 g, 2.09 mmol) and
(1R,2R)-1,2-diamino-1,2-diphenylethane (222 mg, 1.05 mmol)
in dry EtOH (150 mL) was refluxed overnight to afford 1.18 g
(100% yield) of 20 as yellow crystals: mp 235.5–236.1 °C;
[α]2D0
= +57.1° (c 0.0133 in CHCl3); Anal. calc. for
3-tert-Butyl-2-hydroxy-5(6-methoxy-2-oxo-3,4-dipentyl-1,2-dihy-
droquinolin-7-yl)benzaldehyde (18). Compound 17 (5.70 g,
14.4 mmol), 3-tert-butyl-2-hydroxy-5-(4,4,5,5-tetramethyl-1,3,2-
C74H90N4O6·EtOH: C, 77.51; H, 8.22; N, 4.76. Found: C,
77.77; H, 8.02; N, 4.56; δH (400 MHz, CDCl3) 14 (2H, br s,
CONH), 10.39 (2H, br s, OH), 8.43 (2H, s, HCvN), 7.71 (2H,
2064 | Org. Biomol. Chem., 2012, 10, 2059–2067
This journal is © The Royal Society of Chemistry 2012