The Journal of Organic Chemistry
Page 24 of 33
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8.36 (d, J = 8.3 Hz, 1H), 7.70 (dd, J = 7.2, 1.7 Hz, 2H), 7.67 (s, 1H), 7.47 (t, J = 7.4 Hz, 2H), 7.41
(dd, J = 7.7, 1.9 Hz, 2H), 7.33 (td, J = 7.9, 1.5 Hz, 1H), 7.04 (td, J = 7.6, 1.2 Hz, 1H), 6.89 – 6.80 (m,
4H), 5.53 (s, 1H), 3.78 (s, 3H), 1.79 (s, 3H). 13C{1H}NMR (125 MHz, Chloroform-d) δ 168.5, 153.3,
139.3, 139.3, 131.6, 129.7, 129.0, 128.5, 127.3, 123.2, 119.3, 115.7, 115.0, 111.2, 96.1, 80.5, 55.7,
51.6, 24.3. IR (film) νmax 3382, 3063, 2920, 2851, 2361, 1694, 1517, 1445, 1304, 1235, 1034, 821,
760 cm-1. HRMS (ESI-TOF) m/z: Exact mass calcd C24H23N2O2 [M+H]+: 371.1754; Found:
371.1763. MP: 86−88 °C [α]D25 = +134.29 (CHCl3, c = 3.56 for 90% ee). HPLC (Chiralpak IC, n-
hexane/ iso-propanol = 80/20, 1.0 mL/min, 254 nm): tR = 22.04 min (minor), 26.22 min (major).
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(S)-N-(2-(3-(2-Fluorophenyl)-3-((3,4,5-trimethoxyphenyl)amino)prop-1-yn-1-yl)phenyl)-4-
methylbenzenesulfonamide, (8c): Colourless viscous liquid, 97 mg, 87% yield. Rf = 0.35 (30%
EtOAc in hexanes) 1H NMR (500 MHz, Chloroform-d) δ 7.64 (td, J = 7.6, 1.8 Hz, 1H), 7.59 (dd, J =
8.7, 1.1 Hz, 1H), 7.49 (d, J = 8.4 Hz, 2H), 7.42 (dddd, J = 8.3, 7.3, 5.3, 1.8 Hz, 1H), 7.28 – 7.25 (m,
2H), 7.25 – 7.20 (m, 1H), 7.14 (s, 1H), 7.09 (d, J = 7.6 Hz, 2H), 7.01 (td, J = 7.6, 1.1 Hz, 1H), 6.06 (s,
2H), 5.71 (s, 1H), 3.84 (s, 6H), 3.80 (s, 3H), 2.34 (s, 3H). 13C{1H}NMR (125 MHz, Chloroform-d) δ
160.2 (d, J = 247.6 Hz), 154.0, 143.9, 142.4, 138.1, 135.9, 132.0, 131.4, 130.4 (d, J = 8.3 Hz), 129.9,
129.5, 128.7 (d, J = 3.5 Hz), 127.2, 126.5 (d, J = 13.1 Hz), 124.9 (d, J = 3.5 Hz), 124.2, 119.5, 116.2
(d, J = 21.4 Hz), 113.3, 94.9, 92.0, 79.4, 61.1, 56.0, 45.6 (d, J = 3.9 Hz), 21.5. IR (film) νmax 3381,
2924, 2851, 2261, 1605, 1511, 1451, 1401, 1339, 1234, 1157, 1004, 766, 673 cm-1. HRMS (ESI-
TOF) m/z: Exact mass calcd for C31H28FN2O5S [M−H]−: 559.1697; Found: 559.1694. [α]D = −37.6
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(CHCl3, c = 1.9 for 72% ee). HPLC (Chiralpak ID, n-hexane/ iso-propanol = 70/30, 1.0 mL/min, 254
nm): tR = 41.46 min (major), 47.30 min (minor).
(S)-N-(2-(3-(2-Fluorophenyl)-3-((3,4,5-trimethoxyphenyl)amino)prop-1-yn-1-yl)phenyl)
acetamide (8d): Colourless viscous liquid, 71 mg, 79% yield. Rf = 0.38(30% EtOAc in hexanes). 1H
NMR (500 MHz, Chloroform-d) δ 8.37 (d, J = 8.4 Hz, 1H), 7.77 (s, 1H), 7.71 (td, J = 7.6, 1.8 Hz,
1H), 7.39 (td, J = 7.7, 1.8 Hz, 2H), 7.33 (ddd, J = 8.6, 7.5, 1.6 Hz, 1H), 7.25 (td, J = 7.6, 1.2 Hz, 1H),
7.18 (ddd, J = 10.5, 8.2, 1.2 Hz, 1H), 7.03 (td, J = 7.6, 1.2 Hz, 1H), 6.08 (s, 2H), 5.78 (s, 1H), 4.34 (s,
1H), 3.80 (d, J = 17.8 Hz, 9H), 1.94 (s, 3H). 13C{1H}NMR (125 MHz, Chloroform-d) δ 168.4, 160.2
(d, J = 247.6 Hz), 154.0, 142.5, 139.4, 131.5, 131.3, 130.4 (d, J = 8.3 Hz), 130.0, 128.8 (d, J = 3.3
Hz), 126.6 (d, J = 13.1 Hz), 124.9 (d, J = 3.6 Hz), 123.2, 119.3, 116.1 (d, J = 21.3 Hz), 110.9, 94.8,
91.8, 80.2, 61.0, 56.0, 45.5 (d, J = 3.9 Hz), 24.3 IR (film) νmax 3377, 2930, 2851, 2261, 1694, 1601,
1571, 1453, 1304, 1235, 1120, 1007, 752 cm-1. HRMS (ESI-TOF) m/z: Exact mass calcd for
C26H26FN2O4 [M+H]+: 449.1871; Found: 449.1856. [α]D = +50.2 (CHCl3, c = 2.84 for 96% ee).
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HPLC (Chiralpak ID, n-hexane/ iso-propanol = 70/30, 1.0 mL/min, 254 nm): tR = 22.16 min (major),
44.90 min (minor).
(S)-N-(3-(2-(Ethylamino)phenyl)-1-(2-fluorophenyl)prop-2-yn-1-yl)-3,4,5-trimethoxyaniline (8e):
Yellow viscous liquid, 76 mg, 78% yield. Rf = 0.30 (30% EtOAc in hexanes). Yellow oil, 76 mg, 78%
yield. Rf = 0.30 (30% EtOAc in hexanes). 1H NMR (500 MHz, Chloroform-d) δ 7.74 (td, J = 7.6, 1.8
Hz, 1H), 7.40 – 7.32 (m, 1H), 7.28 – 7.08 (m, 4H), 6.66 – 6.44 (m, 2H), 6.06 (s, 2H), 5.78 (s, 1H),
4.53 – 4.00 (m, 2H), 3.79 (d, J = 18.0 Hz, 9H), 3.09 (qd, J = 7.2, 2.5 Hz, 2H), 1.11 (t, J = 7.2 Hz, 3H).
13C{1H}NMR (125 MHz, Chloroform-d) δ 160.3 (d, J = 247.9 Hz), 153.9, 149.3, 142.8, 131.9, 131.1,
130.2, 130.1 (d, J = 8.3 Hz), 129.0 (d, J = 3.5 Hz), 127.1 (d, J = 13.3 Hz), 124.7 (d, J = 3.6 Hz), 115.9
(d, J = 21.4 Hz), 115.9, 109.4, 106.3, 93.1, 92.0, 82.0, 61.0, 55.9, 45.5 (d, J = 4.0 Hz), 37.9, 14.5. IR
(film) νmax 3377, 2930, 2851, 2261, 1694, 1601, 1571, 1453, 1304, 1235, 1120, 1007, 752 cm-1.
HRMS (ESI-TOF) m/z: Exact mass calcd for C26H28FN2O3 [M+H]+: 435.2078; Found: 435.2069.
[α]D25 = +85.7 (CHCl3, c = 1.2 for 94% ee). HPLC (Chiralpak IC, n-hexane/ iso-propanol = 70/30, 1.0
mL/min, 254 nm): tR = 13.11 min (minor), 21.59 min (major).
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