1
97% yield; mp 73–75 °C; [α]D = +19.4 (c = 1.0, CHCl3); H
(CH3)3]; 13C NMR (50 MHz, CDCl3) δ 182.2 (CvS), 174.8
(174.5) (CO), 170.6 (CO), 170.0 (169.7) (CO), 137.6 (Ar),
136.4 (Ar), 128.3 (Ar), 128.2 (Ar), 127.7 (Ar), 127.4 (Ar), 127.2
(Ar), 126.9 (Ar), 82.2 [C(CH3)3], 81.2 [C(CH3)3], 78.1 (77.2)
(OCH), 62.3 (NCH), 59.7 (NCH), 54.2 (NCH), 46.7 (NCH2),
37.6 (CH2CO), 30.0 (CH2), 28.0 [C(CH3)3], 27.8 [C(CH3)3],
25.2 (CH2); MS (ESI) 598 (M + H+, 100%); HRMS exact mass
calculated for [M + H]+ (C32H44O6N3S) requires m/z 598.2945,
found m/z 598.2927.
NMR (200 MHz, CDCl3) δ 8.46–8.18 (1H, m, NH), 7.69–7.13
(7H, m, ArH, 2 × NH), 5.66–5.34 (1H, m, NCH), 4.49–3.58
(4H, m, NCH2, 2 × NCH), 3.23–2.52 (4H, m, CH2CO2tBu,
NCH2), 2.29–1.57 (5H, m, 4 × CHH, NH), 1.40 [18H, s, 2 × C
(CH3)3]; 13C NMR (50 MHz, CDCl3) δ 183.6 (CvS), 175.2
(CO), 173.6 (CO), 169.2 (CO), 138.5 (Ar), 128.8 (Ar), 127.8
(Ar), 126.3 (Ar), 82.4 [C(CH3)3], 82.2 [C(CH3)3], 60.4 (NCH),
55.6 (NCH), 51.2 (NCH), 51.0 (NCH2), 46.9 (NCH2), 36.2
(CH2CO2tBu), 30.3 (CH2), 27.9 [C(CH3)3], 27.9 [C(CH3)3],
25.9 (CH2); MS (ESI) 521 (M + H+, 100%); HRMS exact mass
calculated for [M + H]+ (C26H41O5N4S) requires m/z 521.2792,
found m/z 521.2782.
(S)-2-[(1S,2S)-2-3,5-Bis(trifluoromethyl)phenylcarbamothio-
yloxy]-1,2-diphenylethylcarbamoyl)
pyrrolidinium
2,2,2-
trifluoroacetate (14). White solid; 0.11 g, 91% yield; mp
97–99 °C; [α]D = −9.3 (c = 1.0, CHCl3); IR (film) 3238, 2917,
1
(S)-Di-tert-butyl 2-{3-[(1S,2S)-1,2-diphenyl-2-[(S)-pyrrolidine-
2-carbothioamido]-ethyl]thioureido}succinate (11). White solid;
0.04 g, 98% yield; mp 82–84 °C; [α]D = +21.4 (c = 1.0, CHCl3);
1H NMR (200 MHz, CDCl3) δ 10.86 (1H, br s, NHCvS),
7.73–7.07 (12H, m, ArH, 2 × NH), 6.89–6.38 (1H, m, NCH),
6.21–5.84 (1H, m, NCH), 5.25–4.93 (1H, m, NCH), 4.32–4.01
(1H, m, NCH), 3.28–2.67 (4H, m, CH2CO2tBu, NCH2),
2.47–1.65 (5H, m, 4 × CHH, NH), 1.43 [9H, s, C(CH3)3], 1.39
[9H, s, C(CH3)3]; 13C NMR (50 MHz, CDCl3) δ 205.7 (CvS),
181.5 (NHCvSNH), 170.2 (CO), 169.8 (CO), 137.9 (Ar), 136.9
(Ar), 128.7 (Ar), 128.5 (Ar), 128.1 (Ar), 127.8 (Ar), 82.5
[C(CH3)3], 81.9 [C(CH3)3], 67.9 (NCH), 63.2 (NCH), 62.8
(NCH), 54.1 (NCH), 47.2 (NCH2), 38.0 (CH2CO2tBu), 29.7
(CH2), 28.0 [C(CH3)3], 27.9 [C(CH3)3], 25.8 (CH2); MS
(ESI) 623 (M + H+, 100%); HRMS exact mass calculated for
[M + H]+ (C32H45O4N4S2) requires m/z 613.2877, found m/z
613.2874.
2849, 1735, 1672, 1563, 1379, 1218, 1180, 1136, 772 cm−1; H
NMR (200 MHz, CD3OD) δ 8.18–8.01 (2H, m, ArH),
7.74–6.96 (13H, m, 11 × ArH, 2 × NH), 6.32 (0.6H, d, J =
12 Hz, OCH), 6.14 (0.4H, dd, J = 7.2 Hz and 4.0 Hz, OCH),
4.58–4.46 (0.5H, m, NCH), 4.44–4.26 (0.5H, m, NCH),
4.21–3.98 (1H, m, NCH), 3.31–3.06 (2H, m, NCH2), 2.57–1.63
(6H, m, 4 × CHH, 2 × NH); 13C NMR (50 MHz, CD3OD) δ
188.5 (CvS), 168.4 (q, J = 15.9 Hz, CF3CO2−) 168.7 (168.2)
(CO), 142.8 (143.5) (Ar), 142.2 (142.5) (Ar), 141.7 (141.8)
(Ar), 133.2 (q, J = 33.2 Hz, Ar), 130.2 (Ar), 129.6 (Ar), 129.2
(Ar), 129.1 (Ar), 128.1(Ar), 127.4 (Ar), 124.5 (q, J = 272.1 Hz,
CF3), 119.8 (Ar), 117.4 (Ar), 114.9 (q, J = 243.9 Hz, CF3), 76.9
(80.7) (OCH), 60.7 (m, NCH), 57.9 (58.6) (m, NCH), 47.2
(m, NCH2), 30.6 (m, CH2), 24.5 (m, CH2); MS (ESI) 582
(M + H+, 100%); HRMS exact mass calculated for [M + H]+
(C28H26F6O2N3S) requires m/z 582.1644, found m/z 582.1626.
(S)-N-((1S,2S)-1,2-Diphenyl-2-(3-phenylthioureido) ethyl)
pyrrolidine-2-carboxamide (15). White solid; 0.05 g, 100%
yield; mp 85–88 °C; [α]D = −25.8 (c = 1.0, CHCl3); IR (film)
3303, 2916, 2849, 1735, 1665, 1540, 1465, 1218, 772 cm−1; 1H
NMR (200 MHz, CDCl3) δ 9.04 (1H, s, NH), 8.63 (1H, d, J =
9.4 Hz, NH), 7.86 (1H, d, J = 8.8 Hz, ArH), 7.56–6.15 (15H, m,
14 × ArH and NH), 6.07 (1H, t, J = 9.0 Hz, NCH), 5.29 (1H, t,
J = 9.8 Hz, NCH), 3.67 (1H, dd, J = 4.2 Hz, J = 6.2 Hz, NCH),
3.15–2.63 (3H, m, NCH2, NH), 2.16–1.35 (4H, m, 4 × CHH);
13C NMR (50 MHz, CDCl3) δ 180.8 (CvS), 175.0 (CO), 137.9
(Ar), 137.4 (Ar), 129.1 (Ar), 128.4 (Ar), 128.2 (Ar), 127.5 (Ar),
127.4 (Ar), 127.3 (Ar), 125.9 (Ar), 124.3 (Ar), 63.3 (NCH),
60.2 (NCH), 58.8 (NCH), 46.6 (NCH2), 29.9 (CH2), 25.4 (CH2);
MS (ESI) 445 (M + H+, 100%); HRMS exact mass calculated
for [M + H]+ (C26H29ON4S) requires m/z 445.2057, found m/z
445.2038.
(S)-N-((1S,2S)-2-(3-(3,5-bis(trifluoromethyl)phenyl)thioureido)-
1,2-diphenylethyl)-1-((S)-pyrrolidine-2-carbonyl)pyrrolidine-2-
carboxamide (12). Light yellow solid; 0.07 g, 100% yield; mp
149–151 °C; [α]D = −45.1 (c = 1.0, CH3OH); 1H NMR
(200 MHz, CD3OD) δ 8.24–8.13 (2H, m, 2 × ArH), 7.66–7.59
(1H, m, ArH), 7.36–7.08 (10H, m, ArH), 6.16 (1H, d, J = 9.6
Hz, NCH), 5.40 (1H, d, J = 9.6 Hz, NCH), 4.56–4.41 (1H, m,
NCH), 4.00–3.84 (1H, m, NCH), 3.65–3.44 (2H, m, NCH2),
3.14–2.63 (2H, m, NCH2), 2.33–1.53 (8H, m, 8 × CHH); 13C
NMR (50 MHz, CD3OD) δ 182.6 (CvS), 174.1 (173.9) (CO),
172.9 (172.8) (CO), 143.0 (Ar), 140.0 (Ar), 139.7 (Ar), 132.7
(q, J = 33.1 Hz, Ar), 129.6 (Ar), 129.5 (Ar), 129.1 (Ar), 128.9
(Ar), 128.7 (Ar), 128.6 (Ar), 124.7 (q, J = 272.3 Hz, CF3),
123.5 (Ar), 117.9 (Ar), 63.9 (NCH), 61.7 (NCH), 60.0 (NCH),
59.8 (NCH), 48.2 (NCH2), 48.0 (NCH2), 30.7 (CH2), 30.4
(CH2), 26.7 (CH2), 25.8 (CH2); MS (ESI) 678 (M + H+, 100%);
HRMS exact mass calculated for [M + H]+ (C33H34F6O2N5S)
requires m/z 678.2332, found m/z 678.2322.
(S)-N-((1S,2S)-2-(3-Methyl-3-phenylthioureido)-1,2-diphenyl-
ethyl)pyrrolidine-2-carboxamide (16). White solid; 0.06 g,
100% yield; mp 55–57 °C; [α]D = −112.5 (c = 1.0, CHCl3); IR
(film) 3248, 2916, 2848, 1735, 1651, 1515, 1465, 1218,
(S)-Di-tert-butyl 2-(3-((1S,2S)-1,2-diphenyl-2-((S)-pyrrolidine-
2-carbonyloxy) ethyl)thioureido)succinate (13). White solid;
0.07 g, 95% yield; mp 60–62 °C; [α]D = +16.4 (c = 1.0, CHCl3);
1
772 cm−1; H NMR (200 MHz, CDCl3) δ 8.38 (1H, d, J = 9.0
Hz, NH), 7.62–7.39 (3H, m, ArH), 7.38–6.89 (9H, m, ArH),
6.88–6.69 (3H, m, ArH), 6.48 (1H, d, J = 8.0 Hz, NH), 5.87
(1H, t, J = 8.8 Hz, NCH), 4.99 (1H, t, J = 9.2 Hz, NCH),
3.83–3.35 (4H, m, NCH3, NCH), 3.02–2.57 (3H, m, NCH2,
NH), 2.16–1.91 (1H, m, CHH), 1.79–1.38 (3H, m, 3 × CHH);
13C NMR (50 MHz, CDCl3) δ 181.5 (CvS), 174.8 (CO), 142.6
(Ar), 138.7 (Ar), 138.2 (Ar), 130.4 (Ar), 128.5 (Ar), 128.3 (Ar),
IR (film) 3347, 2916, 2848, 1732, 1556, 1219, 1152, 772 cm−1
;
1H NMR (200 MHz, CDCl3) δ 7.43–6.88 (12H, m, ArH,
2 × NH), 6.19–6.01 (1H, m, NCH), 5.26–5.04 (1H, m, OCH),
3.88–3.68 (1H, m, NCH), 3.18–2.74 (5H, m, CH2CO, NCH2
and NCH), 2.25–2.01 (1H, m, CHH), 1.99–1.57 (4H, m,
3 × CHH and NH), 1.40 [9H, s, C(CH3)3], 1.35 [9H, s, C
5618 | Org. Biomol. Chem., 2012, 10, 5613–5619
This journal is © The Royal Society of Chemistry 2012