R.W. Waller et al. / Tetrahedron 66 (2010) 6496e6507
6503
2:1); IR (film) nmax 3330 (br), 2951, 2930, 2958, 1746, 1662, 1510,
1456 cmꢁ1 1H NMR (CDCl3, 300 MHz)
0.77 (3H, t, J 6.6 Hz,
133.2, 137.6, 166.4, 171.3; HRMS: [MþH]þ, C25H34ClN2O3 requires
;
d
445.2258, found 445.2266.
CH3), 1.05 (3H, t, J 7.5 Hz, propyleCH3), 1.13e1.23 (6H, m, CH2),
t
1.25 (9H, s, Bu), 1.39e1.54 (2H, m, CH2), 1.60e1.72 (2H, m, CH2),
4.4.11. 2-{[tert-Butylcarbamoyl-(4-methoxyphenyl)methyl]methyl-
amino}ethyl benzoate 4k. Yield: 68% (method A), 66% (method C);
colourless oil; Rf 0.40 (Petrol/EtOAc, 2:1); IR (film) nmax 3390 (br),
2.19 (3H, s, NeCH3), 2.25 (2H, q, J 7.5 Hz, C]OeCH2), 2.53e2.71
(2H, m, NeCH2), 2.77 (1H, dd, J 7.3, 5.3 Hz, CH), 4.04 (2H, t, J
6.5 Hz, OeCH2), 6.78 (1H, br s, NH); 13C NMR (75 MHz, CDCl3)
2980, 2970, 2930, 2885, 1716, 1678, 1510, 1452 cmꢁ1 1H NMR
;
d
9.0, 14.0, 22.7, 27.3, 27.5, 28.7, 29.2, 30.0, 38.4, 51.0, 53.3, 62.0,
(CDCl3, 300 MHz) d
1.27 (9H, s, tBu), 2.33 (3H, s, NeCH3), 2.67e2.85
68.9, 172.3, 174.3; HRMS: [MþH]þ, C18H37N2O3 requires
(2H, m, NeCH2), 4.02 (3H, s, OMe), 4.06 (1H, s, CH), 4.32e4.62 (2H,
m, CH2eO), 6.78 (2H, d, J 6.8 Hz, m-PhOMe), 7.04 (1H, br s, NH), 7.17
(2H, d, J 6.8 Hz, AreH), 7.32e7.53 (3H, m, AreH), 8.00 (2H, d, J
329.28040, found 329.28191.
4.4.7. 2-[(1-Cyclohexylcarbamoylheptyl)methylamino]ethyl benzoate
4g. Yield: 48% (method A), 43% (method C); colourless oil; Rf 0.26
(Petrol/EtOAc, 2:1); IR (film) nmax 3400e3250 (br), 2930, 2955,1717,
8.5 Hz, AreH); 13C NMR (75 MHz, CDCl3)
d 28.5, 40.4, 50.6, 53.4,
55.2, 62.3, 75.1, 113.8, 128.1, 128.4, 129.6, 130.1, 130.2, 132.5, 133.1,
159.4, 166.4, 170.9; HRMS: [MþH]þ, C23H31N2O4 requires
399.22837, found 399.22720.
1647, 1510, 1452 cmꢁ1 1H NMR (CDCl3, 300 MHz):
; d 0.86 (3H, t, J
7.0 Hz, CH3), 0.88e1.05 (3H, m, alkyl), 1.20 (9H, m, alkyl), 1.32e1.80
(8H, m, alkyl), 2.27 (3H, s, NeCH3), 2.83e2.97 (3H, m, NeCH2 and
CH), 3.53e3.61 (1H, m, CH), 4.28e4.42 (2H, m, CH2eO), 6.82 (1H, d,
J 8.5 Hz, NH), 7.36e7.41 (2H, m, AreH), 7.47e7.51 (1H, m, AreH)
4.4.12. 2-{[tert-Butylcarbamoyl-(4-nitrophenyl)methyl]methyl-
amino}ethyl benzoate 4l. Yield: 47% (method A), 30% (method C);
orange oil; Rf 0.40 (Petrol/EtOAc, 2:1); IR (film) nmax 3300 (br), 3060,
7.96e8.01 (2H, m, AreH); 13C NMR (75 MHz, CDCl3)
d
14.0, 22.6,
2990, 2895, 2805, 1716, 1682, 1521, 1452 cmꢁ1 1H NMR (CDCl3,
;
24.8, 25.4, 27.3, 27.5, 29.5, 31.7, 32.8, 33.1, 38.4, 47.5, 53.8, 62.6, 68.5,
128.4, 129.6, 130.1, 133.1, 166.5, 171.9; HRMS: [MþH]þ, C24H39N2O3
requires 403.29605, found 403.29553.
300 MHz) d
1.26 (9H, s, tBu), 2.30 (3H, s, NeCH3), 2.67e2.88 (2H, t, J
5.6 Hz NeCH2), 4.18 (1H, s, CH), 4.41(2H, m, CH2eO), 6.98 (1H, br s,
NH), 7.39e7.47 (4H, m, AreH), 7.52e7.57 (1H, m, AreH), 8.01 (2H, d,
J 8.6 Hz, AreH), 8.12 (2H, d, J 8.6 Hz, AreH); 13C NMR (75 MHz,
4.4.8. 3-(1H-Indol-3-yl)-2-[(1-tert-butylcarbamoylheptyl)methyl-
aminoethyl propionate 4h. Yield: 44% (method A); colourless oil;
Rf 0.12 (Petrol/EtOAc, 2:1); IR (film) nmax 3300 (br), 3387 (br),
CDCl3) d 28.5, 40.0, 51.0, 53.8, 61.9, 74.7, 123.5, 128.5, 129.6, 129.9,
130.2, 133.3, 143.0, 147.5, 166.4, 169.1; HRMS: [MþNa]þ,
C22H27N3NaO5 requires 437.19099, found 437.19266.
3020, 2959, 2930, 2858, 1732, 1666, 1514, 1456 cmꢁ1 1H NMR
;
(CDCl3, 300 MHz)
d
0.89 (3H, t, J 6.8 Hz CH3), 1.20e1.32 (8H, m,
4.4.13. 2-[Benzyl-(tert-butylcarbamoyl-p-tolylmethyl)amino]ethyl
benzoate 4m. Yield: 44% (method A); colourless oil; Rf 0.28 (Petrol/
EtOAc, 4:1); IR (film) nmax 3342 (br), 2924, 1717, 1678, 1510,
t
CH2), 1.37 (9H, s, Bu), 1.50e1.64 (1H, m, CHHealkyl), 1.68e1.82
(1H, m, CHHealkyl), 2.26 (3H, s, NeCH3), 2.62e2.72 (2H, m,
NeCH2), 2.75 (2H, t, J 7.5 Hz, COeCH2), 2.87 (1H, t, J 5.4 Hz, CH),
3.13 (2H, t, J 7.5 Hz, C]CeCH2), 4.17 (2H, t, J 5.6 Hz, OeCH2), 6.92
(1H, s, NH), 6.97 (1H, s, C]CH), 7.11 (1H, t, J 7.2 Hz, Ar), 7.18 (1H,
t, J 7.1 Hz, Ar), 7.34 (1H, d, J 7.8 Hz, Ar), 7.69 (1H, d, J 7.7 Hz, Ar),
1364 cmꢁ1; 1H NMR (CDCl3, 300 MHz) 1.26 (9H, s, tBu), 2.34 (3H, s,
d
PheCH3), 2.79e2.98 (2H, m, NeCH2), 3.53e3.58 (1H, d, J 4.7 Hz,
PheCH2), 3.87e3.92 (1H, d, J 4.7 Hz, benzylic CH2), 4.20e4.49 (2H,
m, CH2eO), 4.39 (1H, s, CH), 6.96 (1H, br s, NH), 7.13e7.98 (14H, m,
8.84 (1H, br s, NH indole); 13C NMR (75 MHz, CDCl3)
d
14.1, 20.8,
AreH); 13C NMR (75 MHz, CDCl3)
d 21.2, 28.7, 49.2, 50.9, 56.3, 62.6,
22.7, 27.3, 27.6, 28.8, 29.6, 31.7, 35.1, 38.5, 50.5, 53.4, 62.3, 69.1,
111.4, 114.3, 118.5, 119.1, 121.76, 121.82, 127.1, 136.5, 172.6, 173.5;
HRMS: [MþH]þ, C26H41N3O3 requires 443.31479, found
443.31388.
70.2, 127.4, 128.4, 128.5, 129.0, 129.7, 129.9, 130.2, 132.1, 133.1, 137.6,
138.8, 166.5, 170.8; HRMS: [MþH]þ, C29H35N2O3 requires
459.26475, found 459.26337.
4.4.14. 2-[(1-tert-Butylcarbamoylcyclohexyl)methylamino]ethyl ben-
zoate 4n. Yield: 63% (method A); colourless oil; Rf 0.63 (Petrol/
EtOAc, 2:1); IR (film) nmax 3380 (br), 2973, 2944, 2870, 1710, 1680,
4.4.9. 3-{[1-(2,6-Dimethylphenylcarbamoyl)heptyl]methylamino}
ethyl propionate 4i. Yield: 42% (method A); colourless oil; Rf 0.40
(Petrol/EtOAc, 2:1); IR (film) nmax 3300 (br), 3020, 2955, 2928, 2856,
1505, 1465 cmꢁ1 1H NMR (CDCl3, 300 MHz) 1.19 (9H, s, tBu),
; d
1738, 1674, 1468 cmꢁ1
;
1H NMR (CDCl3, 300 MHz)
d
0.88 (3H, t, J
1.30e1.37 (2H, m, CH2) 1.51e1.91 (8H, m, CH2), 2.21 (3H, s, NeCH3),
2.68 (2H, t, J 6.0 Hz, NeCH2,), 4.28 (2H, t, J 6.1 Hz CH2eO), 6.22 (1H,
br s, NH), 7.04e7.41 (3H, m, Ar), 7.92 (2H, d, J 9.4 Hz, Ar); 13C NMR
6.6 Hz, CH3), 1.02 (3H, t, J 7.5 Hz, COCH2CH3), 1.25e1.58 (10H, m,
CH2), 1.63e1.78 (1H, m, CH2), 1.88e2.00 (1H, m, CH2), 2.21 (6H, s,
AreCH3), 2.45 (3H, s, NeCH3), 2.91 (2H, m, NeCH2,), 3.25 (1H, t, J
6.5 Hz, CH), 4.22 (2H, t, J 5.5 Hz, CH2eO), 7.01 (3H, s, Ar), 8.65 (1H, br
(75 MHz, CDCl3)
d 22.9, 25.9, 28.6, 30.2, 36.0, 49.8, 50.1, 63.7, 66.4,
128.3, 129.9, 130.1, 132.9, 166.3, 174.4; HRMS: [MþH]þ, C21H33N2O3
s, NH); 13C NMR (75 MHz, CDCl3)
d
8.9, 14.1, 18.7, 22.6, 27.33, 27.38,
requires 361.24910, found 361.24790.
29.6, 31.7, 38.8, 54.0, 62.1, 68.6, 126.8, 128.8, 134.1, 134.9, 171.4,
174.4; HRMS: [MþNa]þ, C22H36N2NaO3 requires 399.26235, found
399.26169.
4.4.15. 2-[tert-Butyl-(tert-butylcarbamoyl-p-tolyl-methyl)amino]
ethyl acetate 4o. Yield: 20% (method A); colourless needles mp
90e91 ꢀC (CHCl3); Rf 0.40 (Petrol/EtOAc, 2:1); IR (KBr Disc) nmax
3314 (br), 2968, 2924, 1738, 1670, 1506, 1456 cmꢁ1; 1H NMR (CDCl3,
4.4.10. 2-{[1-(2-Chloro-6-methylphenylcarbamoyl)heptyl]methyl-
amino}ethyl benzoate 4j. Yield: 29% (method A); colourless oil; Rf
0.18 (Petrol/EtOAc, 2:1); IR (film) nmax 3280 (br), 2961, 2919, 2874,
t
t
300 MHz)
d 1.16 (9H, s, Bu), 1.41 (9H, s, Bu), 2.00 (3H, s, CO2CH3),
2.28 (3H, s, CH3 tolyl), 2.30e2.41 (1H, m, NeCHH), 2.81e2.92 (1H,
m, NeCHH), 3.58e3.67 (1H, m, OeCHH), 3.78e3.87 (1H, m,
OeCHH), 4.55 (1H, s, CH), 7.01 (2H, d, J 8.1 Hz, Ph), 7.08 (2H, d, J
1719, 1637, 1467 cmꢁ1 1H NMR (CDCl3, 400 MHz)
; d 0.77 (3H, t, J
6.9 Hz, CH2CH3), 1.16e1.28 (6H, m, CH2), 1.32e1.47 (2H, m, CH2),
1.65e1.75 (1H, CH2), 1.87e1.94 (1H, m, CH2), 2.10 (3H, s, NeCH3),
2.55 (3H, s, PheCH3), 3.13 (2H, t, J 5.6 Hz, NeCH2), 3.53 (1H, dd, J 7.1,
6.0 Hz, CH), 4.45e4.90 (2H, t, J 5.6 Hz, OeCH2), 7.05e7.32 (2H, m,
Ar), 7.44e7.49 (2H, m, AreH), 7.57e7.61 (1H, m, Ar), 7.95e8.00 (1H,
m, AreH), 8.11 (2H, m, AreH), 8.70 (1H, br s, NH); 13C NMR
8.1 Hz, Ph), 7.83 (1H, br s, NH); 13C NMR (75 MHz, CDCl3)
d 21.1, 27.9,
28.7, 42.8, 50.6, 56.7, 65.2, 66.6, 129.5, 130.2, 134.4, 137.3, 170.7,
174.0; HRMS: [MþH]þ, C21H35N2O3 requires 363.26475, found
363.26552.
(100 MHz, CDCl3)
d
13.9, 18.9, 22.5, 27.2, 27.5, 29.3, 31.5, 38.4, 53.6,
4.4.16. 2-[(tert-Butylcarbamoyl-p-tolylmethyl)methylamino]ethyl
62.0, 68.3, 127.0, 127.5, 128.17, 128.23, 129.0, 129.4, 130.0, 132.9,
acetate 4p. Yield: 54% (method B); colourless oil; Rf 0.40 (2:1