1800
G.S. Khan et al. / Tetrahedron 68 (2012) 1790e1801
(230 mg, 1.70 mmol). The mixture was then stirred for 18 h before
the DMF was evaporated in vacuo. The residue was diluted with 5:1
methanol/water (12 mL) and potassium carbonate (235 mg,
1.70 mmol) was added. Silica gel was then added until a consistent
slurry was formed. The solvent was removed to give the crude
product adhered to silica. This silica was then loaded and purified
by flash chromatography (CH2Cl2/MeOH 9:1) to give the title
compound 33 (430 mg, 96%) as a white foam. Rf (MeOH/NH3 9:1)¼
was purified with flash chromatography (CH2Cl2/MeOH 19:1) to
furnish the title compound 36 (194 mg, 90%) as a pale yellow foam.
Rf (CH2Cl2/MeOH 9:1)¼0.66; 1H NMR (400 MHz, CDCl3):
d 0.06 (6H,
s, OSi(CH3)2), 0.89 (9H, s, OSiC(CH3)3), 1.01 (12H, d, J¼6.4 Hz,
N(CH(CH3)2)2), 2.03 (3H, s, NHCOCH3), 3.04 (2H, m, N(CH(CH3)2)2),
3.09 (2H, s, COCH2N), 4.64 (2H, s, ArCH2O), 7.31e7.34 (2H, m, AreH),
7.43 (1H, s, AreH), 7.54 (1H, d, J¼7.6 Hz, AreH), 7.75 (2H, d,
J¼7.6 Hz, AreH), 7.96 (1H, s, AreH), 8.17, 8.73 and 9.62 (3H,
NHCOCH3, NHCOAr and NHCOCH2); 13C NMR (100 MHz, CDCl3):
0.13; 1H NMR (400 MHz, CD3OD):
d 0.10 (6H, s, OSi(CH3)2), 0.94 (9H,
s, OSiC(CH3)3), 1.81 (2H, dt, J¼7.1, 7.6 Hz, CH2CH2CH2), 2.10 (3H, s,
NHCOCH3), 2.26 (6H, s, N(CH3)2), 2.43 (2H, t, J¼7.6 Hz, NCH2), 3.41
(2H, t, J¼7.1 Hz, CONHCH2), 4.69 (2H, s, ArCH2O), 7.36 (1H, s, AreH),
7.42 (1H, s, AreH), 7.86e90 (3H, m, AreH), 7.96 (2H, d, J¼8.3 Hz,
d
ꢂ5.4 (OSi(CH3)2), 18.3 (OSiC(CH3)3), 20.5 (N(CH(CH3)2)2), 24.3
(NHCOCH3), 50.1 (COCH2N and N(CH(CH3)2)2), 64.7 (ArCH2O), 110.5
(AreCH), 113.5 (AreCH), 113.7 (AreCH), 118.1 (AreCH), 122.4
(AreCH), 122.7 (AreCH), 129.3 (AreCH), 135.8 (AreC), 137.8 (AreC),
138.4 (AreC), 138.6 (AreC), 143.1 (AreC), 165.8, 168.9 and 172.2
(C]O); nmax cmꢂ1: 3278 (NeH), 2930 (CeH), 1667 (C]O), 1607,
1523 br, 1455, 1420, 1368, 1280 br, 1256; m/z (ESIþ): 555 (MHþ,
100%), 319 (80%); HRMS found (ESIþ): MHþ 555.3360, C30H47N4O4Si
requires 555.3367.
AreH); 13C NMR (100 MHz, CD3OD):
d
ꢂ5.5 (OSi(CH3)2), 18.2
(OSiC(CH3)3), 23.8 (NHCOCH3), 25.3 (OSiC(CH3)3), 25.7
(CH2CH2CH2), 38.3 (CONHCH2), 44.2 (N(CH3)2), 56.8 (NCH2), 66.7
(ArCH2O), 110.8 (AreCH), 113.8 (AreCH), 114.0 (AreCH), 127.0
(AreCH), 127.4 (AreCH), 136.7 (AreC), 137.3 (AreC), 138.3 (AreC),
138.6 (AreC), 142.7 (AreC), 165.9, 167.2 and 169.6 (C]O); nmax
cmꢂ1: 3429 (NeH), 2952 (CeH), 1670 (C]O), 1620, 1551, 1459 br,
1374, 1287; m/z (FABþ) 527 (MHþ, 72%), 469 (MHþꢂC4H9, 7%), 450
(100%), 265 (20%); HRMS found (FABþ); MHþ 527.3058,
C28H43N4O4Si requires 527.3054. When EDC was used in place of
DIC the yield of amide 33 was 55% and alcohol 34 was obtained as
an off-white foam in 25%. Rf (MeOH/NH3 9:1)¼0.12; 1H NMR
4.5.4. 3-Acetamido-N-(4-(2-(diethylamino)acetamido)phenyl)ben-
zamide 38. Using the same procedure as for 33, with acid 13a
(100 mg, 0.40 mmol) and aniline 37 (30 mg, 0.20 mmol) to give the
crude product, which was purified with flash chromatography
(CH2Cl2/MeOH 19:1) to furnish the title compound 38 (74 mg, 97%),
as a white foam. Rf (CH2Cl2/MeOH 9:1)¼0.51; 1H NMR (400 MHz,
(400 MHz, CD3OD):
d
1.79 (2H, dt, J¼7.2, 7.6 Hz, CH2CH2CH2), 2.08
CDCl3):
d
1.05 (6H, t, J¼7.2 Hz, N(CH2CH3)2), 2.01 (3H, s, NHCOCH3),
(3H, s, COCH3), 2.26 (6H, s, N(CH3)2), 2.42 (2H, t, J¼7.6 Hz, NCH2),
3.40 (2H, t, J¼7.2 Hz, CONHCH2), 4.54 (2H, s, ArCH2O), 7.32 (1H, s,
AreH), 7.40 (1H, s, AreH), 7.86 (2H, t, J¼8.3 Hz, AreH), 7.94 (1H, s,
AreH), 7.97 (2H, t, J¼8.3 Hz, AreH); 13C NMR (100 MHz, CD3OD):
2.61 (4H, q, J¼7.2 Hz, N(CH2CH3)2), 3.11 (2H, s, COCH2N), 7.17 (1H, t,
J¼8.0 Hz AreH), 7.27 (1H, d, J¼8.0 Hz, AreH), 7.41 (1H, d, J¼8.0 Hz,
AreH), 7.56 (2H, d, J¼8.4 Hz, AreH), 7.78 (2H, d, J¼8.4 Hz, AreH),
7.88 (1H, s, AreH), 8.28, 8.65 and 9.56 (3H, NHCOCH3, NHCOAr and
d
24.0 (NHCOCH3), 28.0 (CH2CH2CH2), 39.4 (CONHCH2), 45.3
NHCOCH2); 13C NMR (100 MHz, CDCl3):
d 12.3 (N(CH2CH3)2), 24.3
(N(CH3)2), 58.2 (NCH2), 65.0 (ArCH2O), 113.0 (AreCH), 115.9
(AreCH), 116.4 (AreCH), 128.4 (AreCH), 128.9 (AreCH), 138.5
(AreC), 138.9 (AreC), 140.1 (AreC), 140.4 (AreC), 144.0 (AreC),
167.9, 169.2 and 171.7 (C]O); nmax cmꢂ1: 3275, 2944, 1634, 1544,
1280; m/z (FABþ): 413 (MHþ, 33%), 219 (5%), 154 (100%); HRMS
found (FABþ): MHþ 413.2202 C22H29N4O4 requires 413.2189.
(NHCOCH3), 48.8 (N(CH2CH3)2), 58.0 (COCH2N), 112.4 (AreCH),
116.0 (AreCH), 116.4 (AreCH), 118.9 (AreCH), 128.4 (AreCH), 129.2
(AreCH), 130.0 (AreC), 138.6 (2ꢁ AreC), 140.5 (AreC), 165.6, 169.1
and 170.7 (C]O); nmax cmꢂ1: 3276 (NeH), 2969 (CeH), 1671 (C]
O), 1603, 1516, 1480, 1421, 1286; m/z (FABþ): 383 (MHþ, 100%);
HRMS found (FABþ): MHþ 383.2097, C21H27N4O3 requires
383.2083.
4.5.2. N1-(3-Acetamido-5-((tert-butyldimethylsilyloxy)methyl)phe-
nyl)-N4-(3-morpholinopropyl)terephthalamide 35. Using the same
procedure as for 33, with acid 31c (258 mg, 0.88 mmol) and aniline
32 (130 mg, 0.44 mmol) to give the crude product, which was
purified by flash chromatography (CH2Cl2/MeOH 9:1) to give the
title compound 35 (232 mg, 80%) as a pale yellow foam. Rf (MeOH/
4.5.5. N1-(3-Acetamidophenyl)-N4-(2-morpholinoethyl)tereph-
thalamide 39. Using the same procedure as for 33, with acid 31e
(240 mg, 0.86 mmol) and aniline 37 (65 mg, 0.43 mmol) to give the
crude product, which was purified by flash chromatography
(CH2Cl2/MeOH 9:1) to give the title compound 39 (126 mg, 72%) as
a white foam. Rf (MeOH/NH3 9:1)¼0.93; 1H NMR (400 MHz,
NH3 9:1)¼0.72; 1H NMR (400 MHz, CDCl3):
d 0.02 (6H, s, OSi(CH3)2),
0.85 (9H, s, OSiC(CH3)3),1.72 (2H, p, J¼6.4 Hz, CH2CH2CH2),1.98 (3H,
s, NHCOCH3), 2.39e2.42 (6H, m, CH2N(CH2CH2)2), 3.39 (2H, dt,
J¼4.8, 6.4 Hz, CONHCH2), 3.61 (4H, t, J¼4.0 Hz, O(CH2CH2)2), 4.60
(2H, s, ArCH2O), 7.24 (1H, s, AreH), 7.40 (1H, s, AreH), 7.70 (3H, d,
J¼8.0 Hz, AreH), 7.76 (2H, d, J¼8.4 Hz, AreH), 8.20 (1H, t, J¼4.8 Hz,
CONHCH2), 9.02 and 9.38 (2H, NHCOCH3, NHCOAr); 13C NMR
(CD3)2SO):
d
2.02 (3H, s, NHCOCH3), 2.39 (4H, t, J¼4.4 Hz,
CH2N(CH2CH2)2), 2.50 (2H, m, (CH2CH2)2NHCH2), 3.39 (2H, m,
CONHCH2), 3.61 (4H, t, J¼4.4 Hz, O(CH2CH2)2), 7.22 (1H, t, J¼8.0 Hz,
AreH), 7.30 (1H, d, J¼8.8 Hz, AreH), 7.40 (1H, d, J¼6.8 Hz, AreH),
7.92 (2H, d, J¼6.8 Hz, AreH), 8.0 (2H, d, J¼6.8 Hz, AreH), 8.08 (1H, t,
J¼1.8 Hz, AreH), 8.54 (1H, t, J¼5.8 Hz, CONHCH2), 9.94 and 10.32
(2H, NHCOAr and NHCOCH3); 13C NMR (100 MHz, (CD3)2SO): 23.9
(NHCOCH3), 36.6 (CONHCH2), 53.2 (CH2N(CH2CH2)2), 57.2
((CH2CH2)2NCH2), 66.1 (O(CH2CH2)2), 111.2 (AreCH), 114.6 (AreCH),
115.2 (AreCH), 127.0 (AreCH), 127.6 (AreCH), 128.6 (AreCH), 136.9
(AreC), 137.0 (AreC), 139.1 (AreC), 139.4 (AreC), 164.8, 165.3 and
168.2 (C]O); nmax cmꢂ1: 3304 (NeH), 2941, 1663 (C]O), 1645,
1631, 1604, 1532, 1281; m/z (ESIþ): 411 (MHþ, 100%), 313 (2%), 282
(4%), 242 (3%); HRMS found (ESIþ): MHþ 411.2024, C22H27N4O4
requires 411.2032.
(100 MHz, CDCl3):
d
ꢂ5.6 (OSi(CH3)2), 18.2 (OSiC(CH3)3), 23.8
(CH2CH2CH2), 24.5 (NHCOCH3), 25.7 (OSiC(CH3)3), 39.3 (CONHCH2),
53.4 (CH2N(CH2CH2)2), 57.2 (NCH2CH2), 64.7 (ArCH2O), 66.5
(O(CH2CH2)2), 110.7 (AreCH), 113.7 (AreCH), 113.8 (AreCH), 126.9
(AreCH), 127.4 (AreCH), 137.0 (AreC), 137.3 (AreC), 138.2 (AreC),
138.5 (AreC), 142.7 (AreC), 165.8, 167.1 and 169.6 (C]O); nmax
cmꢂ1: 3266 (NeH), 2930 (CeH), 1670 (C]O),1626,1556, 1457, 1418,
1365, 1294; m/z (ESIþ): 569 (MHþ, 100%), 419 (10%), 341 (2%), 219
(58%); HRMS found (ESIþ): MHþ 569.3146, C30H45N4O5Si requires
569.3159.
4.5.6. N1-(3-Morpholinopropyl)-N4-phenylterephthalamide
41. Using the same procedure as for 33, with acid 31c (220 mg,
0.75 mmol) and aniline 40 (35 mg, 0.38 mmol) to give the crude
product, which was purified by flash chromatography (CH2Cl2/
MeOH 9:1) to give the title compound 246 (129 mg, 94%) as a white
4.5.3. N-3-Acetamido-5-(((tert-butyldimethylsilyloxy)methyl)phe-
nyl)-3-(2-(diisopropylamino)acetamido)benzamide 36. Using the
same procedure as for 33, with acid 13f (217 mg, 0.78 mmol) and
aniline 32 (115 mg, 0.39 mmol) to give the crude product, which