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R.P. McGeary et al. / Tetrahedron 65 (2009) 3990–3997
argon. After stirring overnight at room temperature, the suspension
was evaporated and the residue was purified by silica flash column
chromatography (20% ethyl acetate in petroleum ether), Rf 0.20, to
give 20 as a yellow solid (0.286 g, 54%), mp 118–121 ꢁC; ESI-MS m/z
0 ꢁC under an atmosphere of argon. The suspension was stirred for
a further 30 min before water (13 mL) was added and stirring was
continued for 1 h. The solid was collected, washed with water and
air-dried to yield 23 as almost colourless crystals (4.74 g, 90%), mp
356 [MþNa]þ; nmax 3362, 1664 cmꢀ1
;
1H NMR (500 MHz, CDCl3)
65–67 ꢁC (lit.15 mp 67 ꢁC); 1H NMR (400 MHz, CDCl3)
d 8.81 (1H, t, J
d
8.16 (1H, s, NH), 7.98 (2H, d, J 8.5), 7.91 (2H, d, J 8.5), 7.65 (2H, d, J
2.0), 8.44 (1H, ddd, J 8.2, 2.3, 1.1), 8.34–8.31 (1H, m), 7.67 (1H, t, J
8.0), 7.36 (2H, t, J 8.0), 7.17 (2H, t, J 7.5), 3.82 (2H, d, J 6.5), 1.90–1.96
8.0); 13C NMR (100 MHz, CDCl3)
128.5, 124.3.
d 170.6, 148.4, 134.8, 132.2, 130.0,
(1H, m, J 6.5), 0.88 (6H, d, J 7.0); 13C NMR (125 MHz)
d
164.1, 139.9,
138.7, 137.1, 129.1, 128.1, 128.0, 125.1, 120.3, 77.1, 28.0, 18.4; HRMS
[MþNa]þ calcd for C17H19NNaO4S: 356.0927, found: 356.0920.
4.19. N,N0-Bis(3-nitrophenyl)urea (8)21
4.15. 4-(Phenylcarbamoyl)benzenesulfonic acid sodium salt (21)
A solution of 3-nitrobenzoyl azide 23 (4.74 g, 24.7 mmol) in dry
toluene (50 mL) was heated under reflux under an atmosphere of
argon for 40 min. The solution was allowed to cool before a sus-
pension of 3-nitroaniline 9 (3.42 g, 24.8 mmol) in toluene (150 mL)
was added followed by the addition of a crystal of toluene-4-sul-
fonic acid. The suspension was heated at 120 ꢁC for 3.5 h; upon
cooling the solid was collected, washed with toluene and dried in
vacuo to yield 8 as yellow crystals (6.65 g, 89%), mp 247–251 ꢁC
(lit.21 mp 256–258 ꢁC); ESI-MS m/z 325 [MþNa]þ; 1H NMR
A solution of isobutyl 4-(phenylcarbamoyl)benzenesulfonate 20
(0.057 g, 0.17 mmol) and sodium iodide (0.039 g, 0.26 mmol) in dry
acetone (1 mL) was heated under reflux for 32 h. The resulting
precipitate was collected and washed thoroughly with acetone to
give 21 as a colourless solid (0.043 g, 86%), mp>300 ꢁC; ESI-MS m/z
276 [MꢀNa]ꢀ; nmax 1648 cmꢀ1
;
1H NMR (500 MHz, (CD3)2SO)
10.22 (1H, s, NH, exchanged with D2O), 7.29 (2H, d, J 8.5), 7.77 (2H,
d
d, J 7.7), 7.72 (2H, d, J 8.3), 7.33 (2H, t, J 7.7), 7.08 (1H, t, J 7.3); 13C
(500 MHz, (CD3)2SO)
(2H, m), 7.77–7.75 (2H, m), 7.58 (2H, t, J 8.2); 13C NMR (100 MHz,
(CD3)2SO) 152.4, 148.1, 140.6, 130.1, 124.7, 116.7, 112.5.
d 9.39 (2H, s, NH), 8.55 (2H, t, J 2.1), 7.86–7.84
NMR (125 MHz, (CD3)2SO)
d 165.1, 151.0, 139.1, 134.8, 128.5, 127.2,
125.5, 123.6, 120.4; HRMS [MꢀNaþ] calcd for C13H10NO4S:
d
276.0336, found: 276.0329.
4.20. N,N0-Bis(3-(3-nitrobenzamido)phenyl)urea (7)
4.16. N,N0-Bis(4-(3-((4-isobutoxysulfonyl)benzamido)-
benzamido)phenyl)urea (22)
Urea 8 (2.04 g, 6.80 mmol) was suspended in DMF (30 mL) and
5% palladium on carbon (166 mg) was added. The flask was fitted
with a balloon of hydrogen gas, and the mixture was allowed to stir
for 60 h. The mixture was filtered through CeliteÒ, the catalyst was
washed with DMF and the solvent was evaporated to yield the air-
sensitive N,N0-bis(3-aminophenyl)urea 24. Dry THF (10 mL) and
triethylamine (3.75 mL, 26.9 mmol) were added and the mixture
was cooled to 0 ꢁC. A solution of 3-nitrobenzoyl chloride (2.51 g,
13.6 mmol) in dry THF was added dropwise to the mixture under an
atmosphere of argon. The suspension was allowed to warm to room
temperature and stirring was continued for 12 h. The mixture was
filtered and evaporated. The residue was triturated firstly in CHCl3
and then in saturated NaHCO3 before the solid was collected and
washed with water, then acetone, to yield 7 as aþyellow solid (1.54þg,
42%), mp 170 ꢁC (dec); ESI-MS m/z 541.7 [MþH] , 558.6 [MþNH4] ;
The diamine 13 (0.095 g, 0.20 mmol) was added to a solution of
19 (0.117 g, 0.42 mmol) in dry THF (5 mL) at 0 ꢁC under argon.
Triethylamine (0.080 mL, 0.57 mmol) was added and the reaction
was allowed to warm to room temperature while stirring over-
night. The resulting precipitate was collected, sonicated in satu-
rated NaHCO3 (3 mL) for 2 min and then this was repeated in 5%
HCl solution (3 mL) and finally washed with water and THF to yield
22 as a light yellow solid (0.139 g, 73%), mp 240 ꢁC (dec); ESI-MS m/
z 983 [MþNa]þ; nmax 3296, 1642, 1604, 1532, 1515, 1438, 1225 cmꢀ1
;
1H NMR (500 MHz, (CD3)2SO)
d 10.71 (2H, s, NH), 10.19 (2H, s, NH),
8.61 (2H, s, NH), 8.30 (2H, s), 8.24 (4H, d, J 8.6), 8.09 (4H, d, J 8.6),
8.02 (2H, d, J 8.0), 7.74 (2H, d, J 8.0), 7.69 (4H, d, J 9.0), 7.53 (2H, t, J
7.9), 7.45 (4H, d, J 9.0), 3.91 (4H, d, J 6.3), 1.93–1.85 (2H, m), 0.84
(12H, d, J 6.8); 13C NMR (125 MHz, (CD3)2SO)
d
165.0, 164.2, 152.6,
nmax 3417, 3309, 1684, 1640, 1604, 1539, 1511, 1438, 1345 cmꢀ1
NMR (500 MHz, (CD3)2SO) 10.59 (2H, s, NH), 8.79 (2H, s, NH), 8.79
(2H, s), 8.44–8.40 (4H, m), 8.04 (2H, m), 7.84 (2H, t, J 8.0), 7.40 (2H,
br d, J 7.5), 7.29–7.24 (4H, m); 13C NMR (100 MHz, (CD3)2SO)
163.8,
;
1H
139.6, 138.9, 137.9, 135.9, 135.7, 133.3, 129.0, 128.7, 127.7, 123.3,
122.9, 121.1, 120.0, 118.4, 76.9, 27.5, 18.2; HRMS [MþNa]þ calcd for
C49H48N6NaO11S2: 983.2715, found: 983.2711.
d
d
152.7, 148.0, 140.2, 139.3, 136.5, 134.4, 130.5, 129.3, 126.4, 122.7,
114.6, 114.4, 110.8; HRMS [MþNa]þ calcd for C27H20N6NaO7:
563.1286, found: 563.1311.
4.17. N,N0-Bis(4-(3-(4-sulfobenzamido)benzamido)phenyl)-
urea disodium salt (2)
A suspension of 22 (0.089 g, 0.10 mmol) and sodium iodide
(0.082 g, 0.55 mmol) in dry 2-butanone (1 mL) was heated under
reflux for 2 days. The resulting precipitate was collected, resus-
pended in 2-butanone (3ꢂ2 mL) and filtered to give 2 as a colour-
less solid (0.810 g, 99%), mp>300 ꢁC; ESI-MS m/z 915 [MþNa]þ;
4.21. N,N0-Bis(3-(3-aminobenzamido)phenyl)urea (25)
Compound 7 (0.403 g, 0.75 mmol) was suspended with 5%
palladium on carbon (100 mg) in DMF (15 mL). The flask was fitted
with a balloon of hydrogen gas, and the mixture was allowed to stir
for 36 h. The resulting solution was filtered through CeliteÒ, the
catalyst was washed with DMF (40 mL) and the solvent was
evaporated. The residue was triturated with cold water (10 mL),
collected and dried in vacuo to yield 25 as a colourlesþs solid
(0.325 g, 91%), mp 221 ꢁC (dec); ESI-MS m/z 503 [MþNa] ; nmax
nmax 3280, 1641, 1604, 1537, 1486, 1437, 1224 cmꢀ1 1H NMR
;
(500 MHz, (CD3)2SO) d 10.44 (2H, s, NH), 10.18 (2H, s, NH), 8.64 (2H,
s, NH), 8.31 (2H, s), 8.02 (2H, d, J 7.8), 7.97 (4H, d, J 8.3), 7.76 (4H, d, J
8.3), 7.69 (6H, d, J 8.7), 7.50 (2H, t, J 7.9), 7.45 (4H, d, J 8.9); 13C NMR
(125 MHz, (CD3)2SO)
d 165.2, 165.1, 152.6, 152.2, 139.2, 135.7, 135.6,
135.4, 133.4, 128.6, 127.3, 125.5, 123.2, 122.6, 121.0, 119.9, 118.4.
3281, 1637, 1604, 1538, 1515, 1489, 1438 cmꢀ1 1H NMR (500 MHz,
;
(CD3)2SO)
d, J 8.0), 7.27 (2H, d, J 8.1), 7.21 (2H, t, J 8.0), 7.13 (2H, t, J 7.8), 7.08
(2H, s), 7.06 (2H, d, J 7.7), 6.74 (2H, d, J 7.9), 5.30 (4H, br s, NH2); 13
d 10.04 (2H, s, NH), 8.64 (2H, s, NH), 7.92 (2H, s), 7.34 (2H,
4.18. 3-Nitrobenzoyl azide (23)15
C
A solution of 3-nitrobenzoyl chloride (5.09 g, 27.5 mmol) in dry
acetone (13 mL) was added dropwise over a period of 30 min to
a stirred solution of sodium azide (3.08 g, 46.9 mmol) in water at
NMR (125 MHz, (CD3)2SO) d 166.4, 152.3, 148.6, 139.8, 139.7, 136.0,
128.7, 128.6, 116.7, 114.8, 113.9, 113.2, 113.0, 110.1; HRMS [MþH]þ
calcd for C27H25N6O3: 481.1988, found: 481.1990.