MHz) δ 1.90 (s, 3H, CH3), 2.19 (s, 3H, CH3), 3.02 (s, 3H,
-NCH3), 3.20-3.36 (m, 3H, 3×CH), 4.29 (m, 1H, CH), 5.86
(1H, dCH), 6.31 (d, 1H, CH), 6.91-7.61 (m, 5H, 4H, aromatic
protons and -CONH); HRMS calcd for C16H20N2O2 272.3509,
found, 272.3497.
(500 MHz) δ 1.44 (d, 3H, CH3), 5.10 (m, 1H, CH), 6.47 (dd,
1H, aromatic proton), 7.23-7.34 (m, 5H, aromatic protons),
7.71 (d,1H, aromatic proton), 8.32 (1H, aromatic proton), 10.22
(1H, NH), 12.61 (broad OH); HRMS calcd for C14H14N2O2
242.2799, found, 242.2795.
9: method b: 93% yield; mp 210-212 °C; 96.9% de; IR
(cm-1) 3315 and 3249 (sharp N-H stretching), 1709 (sharp
CdO stretching), 1668 and 1658 (sharp amide CdO stretching);
1H NMR (500 MHz) δ 1.3 (d, CHCH3), 2.9 (S, NCH3),
3.16-3.38 (m, 3H, -CH and -CH2), 4.29 (m, 2H), 5.05 (s,
CH2), 6.1 (d, CH), 7.15-7.36 (m, 9H aromatic protons), 7.75
(d, NH), 8.22 (d, NH); HRMS calcd for C22H25N3O4 395.4621,
found, 395.4623.
10: method b: 88% yield; mp 170-174 °C; 98.7% de; IR
(cm-1): 3430 (broad O-H stretching), 3320 (broad N-H
stretching), 1681 and 1641 (sharp carbonyl stretching); 1H NMR
(500 MHz) δ 2.91 (s, 3H, -NCH3), 3.12-3.75 (m, 3H, 3×CH),
4.12 (m, 1H, CH), 5.17 (d, 1H, -OH), 6.12 (d, CH), 7.14-7.46
(m, 9H, aromatic protons), 8.33 (d, 1H, -CONH); HRMS calcd
for C19H20N2O3 324.3829, found, 324.3826.
14: method b: product was isolated via extractive workup
with EtOAc; 93% yield; mp 95-98 °C; [R]20D -23.62° (c 1.00,
MeOH); IR (cm-1) 3348 and 3330 (sharp N-H stretching),
1736 (sharp CdO strectching), 1679 (sharp amide CdO
stretching); 1H NMR (500 MHz) δ 1.7-1.12 (m, 6H, -CHCH3
and -CH2CH3), 1.35 (s, 9H, C(CH3)3), 2.96 (m, 2H, CH2), 4.01
(m, 3H, CH and -OCH2CH3), 4.85 (m, CH), 6.81 (d, NH),
7.21-7.25 (m, 5 H aromatic protons), 8.16 (d, NH); HRMS
calcd for C19H28N2O5 364.4454, found, 364.4451.
15: method b: 80% yield; mp 58 -61 °C; [R]20 -71.39°
D
(c 1.00, MeOH); IR (cm-1) 3323 (sharp O-H stretching), 3200
1
(broad N-H stretching), 1687 (sharp CdO strectching); H
NMR (DMSO-d6) δ 1.32 (d, 3H, CHCH3), 1.37 (s, 9H,
C(CH3)3), 3.52 (m, 2H, CH2), 3.97 (m, 1H, CH), 4.87 (broad,
1H, OH), 4.93 (q, 1H, -CH), 6.55 (d, NH), 7.15 -7.28 (m,
5H aromatic protons), 8.16 (d, NH); HRMS calcd for
C16H24N2O4 308.3807, found, 308.3804.
16: method b: 76% yield; mp 125 -126 °C; 1H NMR (500
MHz) δ 1.81 (t, 4H), 1.96 (t, 4H), 2.57 (d, 4H), 2.71 (m, 2H),
3.26 (m, 2H), 4.09 (m, 2H), 4.6 (m, 2H), 4.69 (m, 2H), 6.42
(d, 2H, aromatic), 7.03 (t, 2H, aromatic), 7.10 (t, 2H, aromatic),
7.45 (d, 2H, aromatic), 7.52 (d, 2H, aromatic), 7.57 (d, 2H,
aromatic); 13C NMR (500 MHz) δ 40, 40.6, 44.7, 31.76, 32.52,
52.24, 65.4, 101.01, 109.79, 120.43, 124.92, 127.60, 135.22,
169.15; HRMS calcd for C31H36N4O3 512.6576, found, 512.6571.
11: method b: 87% yield; mp 195-197 °C; 98.7% ee; IR
(cm-1) 3400-3200 (broad, O-H and N-H stretching), 1662
1
and 1642 (sharp, amide carbonyl stretching); H NMR (500
MHz) δ 2.93 (s, 3H, -CH3), 3.2 -3.4 (m, 3H, 3×CH), 4.32
(m, 1H CH), 6.43 (d, 1H, CH), 7.09 -7.20 (m, 4H, aromatic
protons), 7.73-7.81 (m, 2H, 2×CH aromatic protons), 8.13 (d,
1H, aromatic proton), 9.75 (d, NH); HRMS calcd for
C18H17N3O5 355.3533, found, 355.3531.
12: method b: 99% yield; mp 105-108 °C; [R]20D -98.51°
(c 1.00, MeOH); IR (KBr cm-1) 3320 (sharp N-H stretching),
1735 (sharp CdO stretching), 1652 (sharp amide CdO stretch-
ing); 1H NMR (500 MHz) δ 1.35 (s, 9H, -C(CH3)3), 1.78 (m,
2H, CH2), 1.9 (s, 3H, SCH3), 2.36 (m, 2H, -CH2), 3.61 (s,
3H,COOH3), 4.10 (m, CH), 5.41 (d, CH), 7.01 (d, NH), 7.31
(m, 5 H aromatic protons), 8.56 (d, NH); HRMS calcd for
C19H28N2O5S 396.5094, found, 396.5091.
Acknowledgment
We thank the physical chemistry department for providing
analytical data and Professors Marvin Miller, William Roush,
and Peter Wipf for helpful discussions during this project.
13: method b: 82% yield; mp 193-195 °C; [R]20D +127.19°
(c 1.00, MeOH); IR (cm-1) 3400-3200 (broad, O-H and N-H
stretching), 1679 (sharp, amide carbonyl stretching); 1H NMR
Received for review September 26, 2008.
OP800240D
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Vol. 13, No. 2, 2009 / Organic Process Research & Development