Full Paper
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756 cm–1. H NMR (500 MHz, CDCl3): δ = 9.95 (s, 1 H), 8.92 (s, 1 H),
9.49rotamer (0.4 H), 8.57–8.55 (d, J = 8.3 Hz, 1 H), 7.97–7.86 (m, 1 H),
8.38–8.36 (d, J = 8.3 Hz, 1 H), 7.85–7.83 (dd, J = 8.07, 1.2 Hz, 1 H), 7.60–7.49 (m, 1 H), 7.24–7.21 (t, J = 7.6 Hz, 1 H), 5.17–5.15 (dd, J =
7.54–7.51 (t, J = 8.3 Hz, 1 H), 7.43–7.39 (m, 4 H), 7.22–7.19 (t, J = 9.0, 2.1 Hz, 1 H), 4.70–4.63 (m, 1 H), 4.47–4.33 (m, 1 H), 3.80–3.70
8.07 Hz, 1 H), 4.72–4.69 (m, 1 H), 4.67–4.64 (m, 1 H), 4.36–4.34 (dd, (m, 3 H), 3.65 (s, 3 H), 3.56–3.53 (dd, J = 16.8, 7.8 Hz, 1 H), 3.44–3.26
J = 8.4, 1.9 Hz, 1 H), 4.02–3.98 (dd, J = 16.6, 7.7 Hz, 1 H), 3.73–3.66
(m, 2 H), 2.51–2.29 (m, 1 H), 2.26–2.14 (m, 3 H), 2.08–2.03 (m, 2 H),
(m, 3 H), 3.56–3.51 (m, 1 H), 3.46–3.43 (dd, J = 17.1, 8.1 Hz, 1 H), 1.97–1.90 (m, 4 H), 1.88–1.77 (m, 2 H), 1.23rotamer (6 H), 1.01rotamer
2.2–2.14 (m, 3 H), 2.12–2.05 (m, 3 H), 2.04–1.95 (m, 2 H), 1.88–1.83
(3 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 176.51, 173.31, 172.28,
(m, 2 H), 1.80–1.74 (m, 2 H), 1.24 (s, 9 H) ppm. 13C NMR (125 MHz, 171.70, 170.98, 136.44, 134.44, 133.53, 129.76, 129.34, 126.77,
CDCl3): δ = 176.74, 172.99, 170.96, 169.16, 136.64, 136.46, 134.65, 125.78, 123.93, 122.38, 62.10, 61.53, 59.95, 52.70, 48.56, 47.10, 38.50,
131.71, 131.14, 129.94, 124.45, 124.29, 123.24, 121.95, 121.47,
117.14, 62.19, 61.94, 59.75, 49.61, 48.51, 47.42, 38.59, 30.39, 29.40,
32.15, 30.89, 29.10, 28.06, 27.24, 24.74, 22.62 ppm. HRMS: calcd. for
27H39O7N4S 563.2534; found 563.2533. calcd. for C27H38O7N4NaS
C
27.23, 26.17, 25.19, 24.28 ppm. HRMS: calcd. for C32H41O6N5BrS 585.2353; found 585.2349.
702.1955; found 702.1952.
(S)-N-(4-Bromophenyl)-1-({2-[(S)-1-(pivaloyl-D-prolyl)pyrrol-
tert-Butyl (R)-2-{(S)-2-[(2-{[(S)-2-(Methoxycarbonyl)pyrrolidin-1-
yl]sulfonyl}phenyl)carbamoyl]pyrrolidine-1-carbonyl}pyrrol-
idine-2-carboxamido]phenyl}sulfonyl)pyrrolidine-2-carbox-
amide (2): Purification by column chromatography (90:10 ethyl
idine-1-carboxylate (12): Purification by column chromatography acetate/petroleum ether; Rf = 0.3) afforded 2 as a white solid (91 %),
(75:25 ethyl acetate/petroleum ether; Rf = 0.5) afforded 12 as a
m.p. 117–118 °C. [α]2D5 = –109.32 (c = 0.16, CHCl3). IR (CHCl3): ν =
˜
viscous liquid (85 %). [α]2D5 = –113.32 (c = 0.1, CHCl3). IR (CHCl3): ν = 3226, 3114, 2978, 2882, 1684, 1607, 1532, 1436, 1322, 1162, 1075,
˜
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3453, 3338, 2973, 2883, 1745, 1695, 1525, 1403, 1163, 1085, 886,
829, 756 cm–1. H NMR (500 MHz, CDCl3): δ = 9.46 (s, 1 H), 9.12 (s,
758 cm–1
9.61rotamer (0.2 H), 8.55–8.39 (m, 1 H), 8.11rotamer (0.2 H), 7.98–
7.84rotamer (0.8 H), 7.62–7.48 (m, 1 H), 7.22–7.16 (t, J = 7.7 Hz, 1 H), J = 7.8 Hz, 1 H), 4.68–4.66 (m, 2 H), 4.43–4.38 (m, 1 H), 4.16 (br. s, 1
.
1H NMR (400 MHz, CDCl3): δ = 9.82rotamer (0.8 H), 1 H), 7.90–7.89 (d, J = 8.1 Hz, 1 H), 7.74–7.73 (d, J = 7.8 Hz, 1 H),
7.45–7.42 (dd, J = 8.1, 1.4 Hz, 1 H), 7.39–7.34 (m, 4 H), 7.26–7.23 (t,
4.69–4.65 (dd, J = 10.4, 5.3 Hz, 1 H), 4.54–4.43 (m, 1 H), 4.39–4.27
(m, 1 H), 3.84–3.78 (m, 1 H), 3.73 (s, 1 H), 3.69 (s, 3 H), 3.54–3.45 (m,
2 H), 3.41–3.25 (m, 2 H), 2.29–2.21 (m, 2 H), 2.18–2.12 (m, 2 H), 2.09–
H), 3.77–3.71 (m, 2 H), 3.65–3.61 (m, 1 H), 3.60–3.54 (m, 1 H), 3.50–
3.44 (m, 1 H), 2.33–2.25 (m, 2 H), 2.21–2.11 (m, 4 H), 2.06–1.98 (m,
2 H), 1.92–1.85 (m, 3 H), 1.82–1.77 (m, 1 H), 1.02 (s, 9 H) ppm. 13C
2.02 (m, 3 H), 1.97–1.88 (m, 4 H), 1.87–1.82 (m, 1 H), 1.42rotamer (7 NMR (125 MHz, CDCl3): δ = 177.23, 172.5, 171.36, 169.53, 136.92,
H), 1.18rotamer (2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 172.89, 136.56, 136.03, 134.14, 131.93, 131.45, 130.28, 128.98, 127.18,
172.65, 172.47, 171.65, 171.02, 170.71, 170.56, 154.31, 153.96,
136.79, 136.26, 134.67, 134.20, 133.62, 130.13, 129.83, 129.73,
129.17, 128.07, 125.99, 125.67, 125.35, 124.50, 124.14, 123.70,
123.58, 123.08, 122.47, 79.80, 79.47, 61.56, 60.06, 59.34, 58.99, 58.34,
57.57, 52.74, 52.59, 52.48, 48.99, 48.59, 48.34, 47.34, 47.03, 46.90,
46.79, 46.38, 32.26, 32.09, 31.21, 30.86, 30.18, 29.60, 29.07, 28.41,
28.04, 24.98, 24.75, 24.56, 23.75, 23.34, 22.37 ppm. HRMS: calcd. for
125.66, 124.26, 121.48, 116.53, 62.86, 61.68, 60.24, 49.06, 48.55,
47.14, 38.48, 32.07, 30.56, 29.43, 28.05, 27.08, 26.83, 26.20, 24.93,
24.52 ppm. HRMS: calcd. C32H41O6N5BrS 702.1955; found 702.1953.
Methyl {[2-((S)-1-{2-[(tert-Butoxycarbonyl)amino]-2-methyl-
propanoyl}pyrrolidine-2-carboxamido)phenyl]sulfonyl}-L-prol-
inate (15): Purification by column chromatography (75:25 ethyl
acetate/petroleum ether; Rf = 0.5) afforded 15 as a white solid
C
27H39O8N4S 579.2483; found 579.2485. calcd. for C27H38O8N4NaS
(97 %), m.p. 149–153 °C. [α]2D5 = –238 (c = 0.1, CHCl3). IR (CHCl3): ν =
˜
601.2303; found 601.2298.
3330, 3019, 2400, 1745, 1708, 1634, 1584, 1524, 1437, 1338, 1215,
tert-Butyl (R)-2-((S)-2-{[2-({(S)-2-[(4-Bromophenyl)carbamoyl]- 771 cm–1. H NMR (500 MHz, CDCl3): δ = 9.90 (s, 1 H), 8.42 (s, 1 H),
1
pyrrolidin-1-yl}sulfonyl)phenyl]carbamoyl}pyrrolidine-1-carb-
onyl)pyrrolidine-1-carboxylate (13): Purification by column chro-
matography (70:30 ethyl acetate/petroleum ether; Rf = 0.3) afforded
7.82–7.81 (d, J = 7.8 Hz, 1 H), 7.56–7.53 (t, J = 7.1 Hz, 1 H), 7.22–
7.19 (t, J = 7.8 Hz, 1 H), 7.00 (s, 1 H), 5.01 (br. s, 1 H), 4.61 (br. s, 1
H), 4.22–4.19 (m, 1 H), 3.79 (s, 3 H), 3.45 (br. s, 1 H), 2.70 (br. s, 2 H),
13 as a white solid (83 %), m.p. 126–128 °C. [α]2D5 = –83.5 (c = 0.14, 2.16–2.09 (m, 4 H), 1.99–1.76 (m, 4 H), 1.51 (s, 6 H), 1.42 (s, 9 H) ppm.
CHCl3). IR (CHCl3): ν = 3286, 2981, 2878, 1697, 1680, 1540, 1400, 13C NMR (125 MHz, CDCl3): δ = 172.93, 171.33, 154.05, 136.77,
˜
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1158, 756 cm–1. H NMR (400 MHz, CDCl3): δ = 10.08rotamer (0.3 H), 134.46, 129.83, 124.07, 123.10, 79.84, 63.76, 61.95, 56.62, 49.53,
9.68rotamer (0.5 H), 8.85rotamer (0.7 H), 8.50rotamer (0.3 H), 7.96–7.86
48.23, 30.62, 28.50, 28.26, 26.25, 25.99, 25.42, 25.10, 24.29 ppm.
(dd, J = 7.5, 1.2 Hz, 1 H), 7.73–7.55 (m, 1 H), 7.50–7.37 (m, 5 H), HRMS: calcd. C26H39O8N4S 567.2483; found 567.2485. calcd.
7.27–7.21 (m, 1 H), 4.74–4.50 (m, 1 H), 4.48–4.37 (m, 1 H), 4.34–4.09 C26H38O8N4NaS 589.2303; found 589.2302.
(m, 1 H), 3.90–3.70 (m, 1 H), 3.67–3.57 (m, 1 H), 3.56–3.38 (m, 4 H),
tert-Butyl [1-((S)-2-{[2-({(S)-2-[(4-Bromophenyl)carbamoyl]pyrr-
2.33–2.16 (m, 4 H), 2.14–2.02 (m, 2 H), 1.99–1.84 (m, 4 H), 1.83–1.79
olidin-1-yl}sulfonyl)phenyl]carbamoyl}pyrrolidin-1-yl)-2-
(m, 2 H), 1.39rotamer (4 H), 1.20rotamer (5 H) ppm. 13C NMR (100 MHz,
methyl-1-oxopropan-2-yl]carbamate (3): Purification by column
CDCl3): δ = 172.59, 172.36, 171.00, 170.15, 169.33, 169.11, 154.65,
chromatography (75:25 ethyl acetate/petroleum ether; Rf = 0.5) af-
153.82, 136.82, 136.27, 134.73, 134.22, 131.83, 131.60, 129.83,
forded 3 as a white crystalline solid (92 %), m.p. 216–218 °C. [α]2D6
=
128.01, 126.63, 125.40, 124.07, 122.97, 121.56, 117.11, 116.76, 79.94,
79.87, 62.59, 62.18, 61.82, 58.56, 58.01, 50.19, 49.34, 47.18, 46.92,
46.53, 41.31, 30.40, 30.22, 29.27, 29.13, 28.80, 28.43, 28.11, 25.30,
24.79, 24.66, 24.58, 24.42, 23.53, 22.58 ppm. HRMS: calcd. for
C32H41O7N5BrS 718.1905; found 718.1901.
–248 (c = 0.1, CHCl3). IR (CHCl3): ν = 3415, 2981, 1687, 1623, 1529,
˜
1436, 1161, 1076, 826, 759 cm–1 1H NMR (400 MHz, CDCl3): δ =
.
9.93 (s, 1 H), 8.93 (s, 1 H), 8.31 (br. s, 1 H), 7.87–7.85 (d, J = 8.0 Hz,
1 H), 7.52–7.48 (t, J = 7.6 Hz, 1 H), 7.39 (s, 4 H), 7.22–7.18 (t, J =
8.0 Hz, 1 H), 4.95 (br. s, 1 H), 4.64 (br. s, 1 H), 4.43–4.37 (m, 1 H),
3.81–3.71 (m, 3 H), 3.53–3.50 (m, 1 H), 2.22–2.09 (m, 4 H), 2.02–1.82
Methyl ({2-[(S)-1-(Pivaloyl-
phenyl}sulfonyl)-
tography (95:5 ethyl acetate/petroleum ether; Rf = 0.3) afforded 14
as a viscous liquid (69 %). [α]2D5 = –105.89 (c = 0.2, CHCl3). IR (CHCl3): 123.49, 121.95, 116.99, 80.11, 63.75, 62.06, 56.61, 49.65, 48.29, 30.64,
ν = 3414, 2971, 1744, 1649, 1609, 1522, 1428, 1332, 1159, 1086, 28.25, 26.04, 25.19, 24.35 ppm. HRMS: calcd. C31H41O7N5BrS
1H NMR (500 MHz, CDCl3): δ = 9.98rotamer (0.6 H), 706.1905; found 706.1906.
D-prolyl)pyrrolidine-2-carboxamido]-
L
-prolinate (14): Purification by column chroma- (m, 4 H), 1.50 (s, 6 H), 1.42 (s, 9 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 173.04, 171.32, 169.26, 136.67, 134.55, 131.61, 129.99, 124.32,
˜
760 cm–1
.
Eur. J. Org. Chem. 2016, 1380–1388
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© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim