European Journal of Organic Chemistry
10.1002/ejoc.201601221
FULL PAPER
filtered and solvent was removed in vacuo to give the crude product
which was purified by column chromatography (c-Hex/EtOAc; 1:1) to give
triazole 7 as a white solid (50 mg, 73%). M.p. = 76-79 °C. Rf = 0.4 (c-
Hex/EtOAc; 1:2). IR (film): νmax = 3302, 3137, 3062, 3034, 2927, 2859,
7.52-7.58 (m, 2H, ArH) 7.60-7.66 (m, 1H, ArH) 7.84 (d, J = 7.5 Hz, 2H,
ArH) 8.07 (s, 1H, ArH) ppm. 13C NMR (100 MHz, CDCl3): δ = 22.0 (CH2)
29.1 (CH2) 32.9 (CH2) 38.0 (CH2) 48.8 (CH) 49.9 (CH2) 52.2 (CH3) 56.8
(CH) 67.0 (CH2) 127.2 (CH) 127.5 (CH) 127.6 (CH) 128.0 (CH) 128.2
(CH) 128.5 (CH) 128.7 (CH) 129.2 (CH) 129.4 (CH) 130.6 (CH) 133.6
(CH) 136.1 (C) 136.2 (C) 139.9 (2 × C) 145.1 (CH) 156.1 (CO) 161.2
(CO) 171.0 (CO) ppm. HRMS (ES+) C34H37N5O7NaS (MNa+) calcd.
682.2311; found 682.2311. [α]D = ‒6 (c = 0.1, CH2Cl2).
1713, 1663, 1532, 1447, 1307, 1287, 1236, 1146, 1086 cm‒1 1H NMR
.
(500 MHz, CDCl3): δ = 1.20-1.34 (m, 2H, CH2) 1.49-1.70 (m, 2H, CH2)
1.76-1.96 (m, 2H, CH2) 2.91 (dd, J = 14.0, 7.5 Hz, 1H, CH2) 3.05 (dd, J =
14.0, 7.5 Hz, 1H, CH2) 4.26-4.37 (m, 2H, CH2) 4.40 (app. q, J = 7.5 Hz,
1H, CH) 4.59-4.67 (m, 1H, CH) 4.98-5.08 (m, 2H, CH2) 6.00 (d, J = 8.0
Hz, 1H, NH) 6.21 (dd, J = 15.0, 1.5 Hz, 1H, CH) 6.45 (d, J = 7.5 Hz, 1H,
NH) 6.79 (dd, J = 15.0, 4.5 Hz, 1H, CH) 7.08-7.12 (m, 2H, ArH) 7.13-7.16
(m, 3H, ArH) 7.22-7.35 (m, 6H, ArH) 7.36-7.41 (m, 2H, ArH) 7.50-7.55 (m,
2H, ArH) 7.60 (t, J = 7.5 Hz, 1H, ArH) 7.73 (s, 1H, ArH) 7.80 (d, J = 7.0
Hz, 2H, ArH) 7.84 (d, J = 7.5 Hz, 2H, ArH) ppm. 13C NMR (125 MHz,
CDCl3): δ = 21.9 (CH2) 29.2 (CH2) 32.3 (CH2) 38.2 (CH2) 49.2 (CH2) 49.3
(CH) 57.0 (CH) 67.1 (CH2) 119.9 (CH) 125.9 (CH) 127.2 (CH) 127.7 (CH)
128.0 (CH) 128.2 (CH) 128.4 (CH) 128.6 (CH) 128.8 (CH) 129.0 (CH)
129.3 (CH) 129.5 (CH) 130.4 (C) 130.6 (CH) 133.7 (CH) 136.3 (C) 136.5
(C) 140.1 (C) 145.4 (CH) 148.0 (C) 156.4 (CO) 171.4 (CO) ppm. HRMS
Benzyl
{(S)-1-[((S,E)-7-(4-(hydroxymethyl)-1H-1,2,3-triazol-1-yl)-1-
(phenylsulfonyl)hept-1-en-3-yl)amino]-1-oxo-3-phenylpropan-2-
yl}carbamate 10: As per general procedure: azide 4[16] (30 mg, 0.05
mmol, 1.0 equiv.), propargyl alcohol (13.5 μL, 0.23 mmol, 4.5 equiv.),
CH2Cl2/H2O; 1:1 (1 mL), CuSO4∙5H2O (1 mg, 0.004 mmol, 0.1 equiv.)
and sodium ascorbate (2 mg, 0.01 mmol, 0.2 equiv.). Purification by
column chromatography (CH2Cl2/MeOH; 15:1) gave triazole 10 as a
white solid (30 mg, 91%). M.p. = 46-48 °C. Rf = 0.3 (CH2Cl2/MeOH; 15:1).
IR (film): νmax = 3295, 3062, 2927, 2860, 1707, 1663, 1536, 1447, 1307,
1287, 1259, 1145, 1085, 1052 cm‒1
1.04-1.34 (m, 2H, CH2) 1.38-1.66 (m, 2H, CH2) 1.74-1.96 (m, 2H, CH2)
2.88 (s (br), 1H, OH) 2.94-3.08 (m, 2H, CH2) 4.23-4.45 (m, 3H, CH2
.
1H NMR (400 MHz, CDCl3): δ =
(ES+) C38H39N5O5NaS (MNa+) calcd. 700.2570; found 700.2554. [α]D
=
‒26 (c = 0.1, CH2Cl2). Anal. calcd. C38H39N5O5S: C, 67.34; H, 5.80; N,
+
10.33; found C, 67.07; H, 5.83; N, 9.98.
CH) 4.52-4.63 (m, 1H, CH) 4.76 (s, 2H, CH2) 5.00-5.10 (m, 2H, CH2) 5.77
(s, 1H, NH) 6.06 (d, J = 15.0 Hz, 1H, CH) 6.18 (d, J = 8.5 Hz, 1H, NH)
6.72 (dd, J = 15.0, 4.5 Hz, 1H, CH) 7.13-7.24 (m, 5H, ArH) 7.25-7.37 (m,
5H, ArH) 7.47-7.59 (m, 3H, ArH) 7.64 (t, J = 7.5 Hz, 1H, ArH) 7.84 (d, J =
7.5 Hz, 2H, ArH) ppm. 13C NMR (100 MHz, CDCl3): δ = 21.8 (CH2) 29.0
(CH2) 32.5 (CH2) 38.4 (CH2) 49.0 (CH) 49.4 (CH2) 56.4 (CH + CH2) 67.1
(CH2) 127.1 (CH) 127.6 (CH) 127.9 (2 × CH) 128.2 (CH) 128.5 (CH)
128.6 (CH) 129.2 (CH) 129.3 (CH) 130.4 (CH) 133.6 (CH) 136.1 (C)
136.2 (C) 140.0 (2 × CH) 145.5 (CH) 156.2 (CO) 171.2 (CO) ppm. HRMS
(ES+) C33H37N5O6NaS (MNa+) calcd. 654.2362; found 654.2348. [α]D = ‒6
(c = 0.1, CH2Cl2).
Benzyl
{(S)-1-[((S,E)-7-(4-hexyl-1H-1,2,3-triazol-1-yl)-1-
(phenylsulfonyl)hept-1-en-3-yl)amino]-1-oxo-3-phenylpropan-2-
yl}carbamate 8: As per general procedure: azide 4[16] (30 mg, 0.05 mmol,
1.0 equiv.), n-octyne (10 μL, 0.06 mmol, 1.2 equiv.), CH2Cl2/H2O; 1:1 (1
mL), CuSO4∙5H2O (1 mg, 0.004 mmol, 0.1 equiv.) and sodium ascorbate
(3 mg, 0.015 mmol, 0.3 equiv.). Purification by column chromatography
(c-Hex/EtOAc; 1:1) gave triazole 8 as a white solid (31 mg, 87%). M.p. =
88-90 °C. Rf = 0.4 (c-Hex/EtOAc; 1:2). IR (film): νmax = 3306, 2927, 2857,
1712, 1661, 1530, 1447, 1305, 1256, 1147, 1085, 1053, 1028, 749 cm‒1
.
1H NMR (500 MHz, CDCl3): δ = 0.87 (t, J = 7.0 Hz, 3H, CH3) 1.14-1.90
(m, 14H, CH2) 2.68 (t, J = 8.0 Hz, 2H, CH2) 2.95 (dd, J = 14.0, 8.0 Hz, 1H,
CH2) 3.08 (dd, J = 14.0, 6.5 Hz, 1H, CH2) 4.18-4.31 (m, 2H, CH2) 4.38
(app. q, J = 7.5 Hz, 1H, CH) 4.56-4.64 (m, 1H, CH) 5.04 (s, 2H, CH2)
6.03 (d, J = 8.0 Hz, 1H, NH) 6.22 (d, J = 15.0 Hz, 1H, CH) 6.39 (s (br.),
1H, NH) 6.78 (dd, J = 15.0, 4.5 Hz, 1H, CH) 7.16-7.34 (m, 11H, ArH)
7.51-7.56 (m, 2H, ArH) 7.62 (t, J = 7.5 Hz, 1H, ArH) 7.85 (d, J = 7.5 Hz,
2H, ArH) ppm. 13C NMR (125 MHz, CDCl3): δ = 14.2 (CH3) 21.9 (CH2)
22.7 (CH2) 25.8 (CH2) 29.1 (CH2) 29.3 (CH2) 29.5 (CH2) 31.7 (CH2) 32.3
(CH2) 38.2 (CH2) 48.9 (CH2) 49.3 (CH) 57.0 (CH) 67.1 (CH2) 120.8 (CH)
127.2 (CH) 127.7 (CH) 128.0 (CH) 128.2 (CH) 128.6 (CH) 128.8 (CH)
129.3 (CH) 129.4 (CH) 130.6 (CH) 133.6 (CH) 136.3 (C) 136.6 (C) 140.2
(C) 145.3 (CH) 148.8 (C) 156.4 (CO) 171.3 (CO) ppm. HRMS (ES+)
C38H48N5O5S (MH+) calcd. 686.3376; found 686.3375. [α]D = ‒22 (c = 0.1,
CH2Cl2).
{1-[(S,E)-5-((S)-2-(((Benzyloxy)carbonyl)amino)-3-
phenylpropanamido)-7-(phenylsulfonyl)hept-6-en-1-yl]-1H-1,2,3-
triazol-4-yl}methyl
5-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-
d]imidazol-4-yl]pentanoate 11: Azide 4[16] (35 mg, 0.06 mmol, 1.0
equiv.), biotin ester alkyne[26] (17 mg, 0.06 mmol, 1.0 equiv.) and
CuSO4∙5H2O (1 mg, 0.005 mmol, 0.05 equiv.) was vigorously stirred in
CH2Cl2/H2O; 1:1 (2 mL). Na ascorbate (4 mg, 0.02 mmol, 0.3 equiv.) was
added and the mixture was left to stir for 48 hours. Solvent was removed
in vacuo and the crude product was purified by column chromatography
(CH2Cl2/MeOH; 4:1) to give triazole 11 as a white powdery solid (51 mg,
>95%). M.p. = 65-68 °C. Rf = 0.6 (CH2Cl2/MeOH; 4:1). IR (film): νmax
3274, 3061, 2928, 2860, 1699, 1539, 1497, 1455, 1447, 1307, 1287,
1265, 1146, 1086, 735 cm‒1 1H NMR (600 MHz, CDCl3): δ = 1.21-1.31
=
.
(m, 4H, CH2) 1.32-1.40 (m, 2H, CH2) 1.44-1.69 (m, 4H, CH2) 1.75-1.91
(m, 2H, CH2) 2.32 (t, J = 7.0 Hz, 2H, CH2) 2.65 (d, J = 13.0 Hz, 1H, CH2)
2.84 (dd, J = 13.0, 5.0 Hz, 1H, CH2) 2.93 (dd, J = 13.5, 7.5 Hz, 1H, CH2)
3.00 (dd, J = 13.5, 7.5 Hz, 1H, CH2) 3.08 (td, J = 7.5, 4.5 Hz, 1H, CH)
4.19-4.23 (m, 1H, CH) 4.23-4.30 (m, 2H, CH2) 4.40-4.44 (m, 1H, CH)
4.48 (app. q, J = 7.5 Hz, 1H, CH) 4.54-4.61 (m, 1H, CH) 5.00 (d, J = 12.5
Hz, 1H, CH2) 5.04 (d, J = 12.5 Hz, 1H, CH2) 5.19 (d, J = 13.0 Hz, 1H,
CH2) 5.22 (d, J = 13.0 Hz, 1H, CH2) 5.52 (s, 1H, NH) 5.96 (s, 1H, NH)
6.08 (d, J = 15.0 Hz, 1H, CH) 6.13 (d, J = 8.0 Hz, 1H, NH) 6.76 (dd, J =
15.0, 4.5 Hz, 1H, CH) 7.08-7.20 (m, 5H, ArH) 7.25 (d, J = 7.0 Hz, 2H,
ArH) 7.27-7.33 (m, 3H, ArH) 7.36 (d, J = 8.0 Hz, 1H, NH) 7.55 (app. t, J =
7.5 Hz, 2H ArH) 7.63 (t, J = 7.5 Hz, 1H, ArH) 7.67 (s, 1H, ArH) 7.83 (d, J
= 7.5 Hz, 2H, ArH) ppm. 13C NMR (150 MHz, CDCl3): δ = 22.2 (CH2) 24.7
(CH2) 28.0 (2 × CH2) 29.4 (CH2) 32.9 (CH2) 32.9 (CH2) 33.7 (CH2) 38.5
(CH2) 40.6 (CH2) 49.1 (CH) 49.7 (CH2) 55.4 (CH) 56.4 (CH) 57.6 (CH2)
60.1 (CH) 61.8 (CH) 66.9 (CH2) 124.0 (CH) 127.0 (CH) 127.6 (CH) 127.8
(CH) 128.1 (CH) 128.5 (CH) 128.6 (CH) 129.27 (CH) 129.31 (CH) 130.2
(CH) 133.5 (CH) 136.2 (C) 136.4 (C) 140.1 (C) 142.9 (C) 145.7 (CH)
Methyl
1-{(S,E)-5-((S)-2-[((benzyloxy)carbonyl)amino)-3-
phenylpropanamido]-7-(phenylsulfonyl)hept-6-en-1-yl}-1H-1,2,3-
triazole-4-carboxylate 9: As per general procedure: azide 4[16] (40 mg,
0.07 mmol, 1.0 equiv.), methyl propiolate (9 μL, 0.11 mmol, 1.5 equiv.),
CH2Cl2/H2O; 1:1 (1 mL), CuSO4∙5H2O (1 mg, 0.004 mmol, 0.05 equiv.)
and sodium ascorbate (2 mg, 0.01 mmol, 0.1 equiv.). Purification by
column chromatography (c-Hex/EtOAc; 1:1) gave triazole 9 as a white
solid (30 mg, 65%). M.p. = 61-63 °C. Rf = 0.4 (c-Hex/EtOAc; 1:3). IR
(film): νmax = 3308, 3140, 3061, 3033, 2951, 2927, 2856, 1721, 1665,
1531, 1446, 1371, 1307, 1288, 1230, 1146, 1086, 1044 cm‒1 1H NMR
.
(400 MHz, CDCl3): δ = 1.18-1.35 (m, 2H, CH2) 1.40 -1.66 (m, 2H, CH2)
1.74-1.97 (m, 2H, CH2) 2.97 (dd, J = 14.0, 7.0 Hz, 1H, CH2) 3.04 (dd, J =
14.0, 7.0 Hz, 1H, CH2) 3.90 (s, 3H, CH3) 4.24-4.40 (m, 3H, CH2 + CH)
4.60-4.68 (m, 1H, CH) 5.02 (s, 2H, CH2) 5.65 (d, J = 7.5 Hz, 1H, NH)
6.14 (dd, J = 15.0, 1.5 Hz, 1H, CH) 6.35 (d, J = 8.5 Hz, 1H, NH) 6.77 (dd,
J = 15.0, 4.5 Hz, 1H, CH) 7.12-7.22 (m, 5H, ArH) 7.23-7.34 (m, 5H, ArH)
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