Experimental Section

General procedure 1: Optimized reaction. xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx

Shai273 : 73% yield (780 mg, 3.13 mmol) Sólido pardo. MP: 59.7 – 63.2°C. 1H NMR (300 MHz,
Acetone): δ 8.23 (d, J = 6.2 Hz, 1H), 7.83 (dd, J = 7.9, 0.8 Hz, 1H), 7.37 (dd, J = 7.9, 6.4 Hz, 1H),
4.42 (q, J = 7.1 Hz, 2H), 4.04 (dt, J = 13.9, 7.0 Hz, 1H), 1.46 – 1.36 (m, 9H). 13C NMR (75 MHz,
Acetone): δ 171.67, 163.12, 136.34, 124.16, 122.34, 120.44, 108.94, 61.71, 28.37, 20.60, 14.56.
HRMS (ESI): m/z calcd: [M + H]+. for xxxxxxx, found xxxxx. (DCM/MeOH 9:1)
Shai276: 67% yield (60 mg, 0,2 mmol) Sólido branco. MP: 78.0 – 82.2 °C. 1H NMR (300 MHz,
CDCl3): δ 7.95 (d, J = 8.5 Hz, 1H), 6.34 (d, J = 8.5 Hz, 1H), 4.36 (q, J = 7.1 Hz, 2H), 3.93 (q, J =
13.9, 6.9 Hz, 1H), 3.49 (t, J = 6.6 Hz, 4H), 2.05 – 1.97 (m, 4H), 1.41 (t, J = 7.1 Hz, 3H), 1.34 (d, J
= 7.0 Hz, 6H). 13C NMR (75 MHz, CDCl 3): δ 166.10, 164.50, 160.73, 155.01, 132.17, 106.66,
106.24, 104.08, 60.24, 47.19, 29.81, 27.38, 25.62, 20.84, 14.50. HRMS (ESI): m/z calcd: [M + H]+
for C17H23N2O3+ 303.1703, found 303.1707. (Hex/Acto 9:1)
Shai279a: 37% yield (34 mg, 0.11 mmol) Sólido amarelo. MP: 58.8 – 61.2°C. 1H NMR (300 MHz,
CDCl3): δ 7.92 (d, J = 8.4 Hz, 1H), 6.37 (d, J = 8.4 Hz, 1H), 4.36 (q, J = 7.1 Hz, 2H), 3.93 (qt, J =
13.9, 6.9 Hz, 1H), 3.35 (dd, J = 11.6, 6.8 Hz, 2H), 1.69 – 1.55 (m, 4H), 1.41 (t, J = 7.1 Hz, 3H),
1.34 (d, J = 7.0 Hz, 6H), 0.96 (t, J = 7.3 Hz, 3H). 13C NMR (75 MHz, CDCl 3): δ 166.55, 164.41,
160.54, 156.46, 132.56, 107.66, 106.76, 104.73, 60.33, 42.20, 31.78, 27.43, 20.82, 20.34, 14.52,
14.04. HRMS (ESI): m/z calcd: [M + H]+: for C17H25N2O3+ 305.1860, found 305.1857. (Hex/Acto
9:1)
Shai279b: 30% yield (29 mg, 0.09 mmol) Óleo amarelo. 1H NMR (300 MHz, CDCl3): δ 7.68 (d, J
= 2.5 Hz, 1H), 7.46 (d, J = 2.6 Hz, 1H), 4.39 (q, J = 7.1 Hz, 2H), 3.96 (dt, J = 13.8, 6.9 Hz, 1H),
3.16 (t, J = 7.0 Hz, 2H), 1.71 – 1.59 (m, 2H), 1.43 (t, J = 7.1 Hz, 5H), 1.36 (d, J = 6.9 Hz, 6H), 0.97
(t, J = 7.3 Hz, 3H).. 13C NMR (75 MHz, CDCl 3): δ 171.37, 164.23, 154.62, 143.04, 131.06, 119.12,
113.13, 106.25, 60.46, 44.54, 31.64, 29.84, 27.87, 20.64, 20.41, 14.53, 14.04. HRMS (ESI): m/z
calcd: [M + H]+: for C17H25N2O3+ 305.1860, found 305.1861. (Hex/Acto 9:1)
Shai284: 31% yield (33mg, 0.10 mmol) Sólido Branco. MP: 92.9 – 96.6°C. 1H NMR (300 MHz,
CDCl3): δ 8.03 (d, J = 8.6 Hz, 1H), 6.65 (d, J = 8.6 Hz, 1H), 4.38 (q, J = 7.1 Hz, 2H), 3.95 (qt, J =
13.9, 7.0 Hz, 1H), 3.87 – 3.80 (m, 4H), 3.58 – 3.51 (m, 4H), 1.42 (t, J = 7.1 Hz, 3H), 1.35 (d, J =
7.0 Hz, 6H).13C NMR (75 MHz, CDCl3): δ 167.65, 164.23, 160.06, 157.00, 132.77, 108.98, 106.65,
104.31, 66.80, 60.43, 46.20, 29.83, 27.47, 20.77, 14.51. HRMS (ESI): m/z calcd [M + H]+: for
C17H23N2O4+ 319.1652, found 319.1660. (Hex/Acto 9:1)
Shai287: 33% yield (39 mg, 0.10 mmol) Sólido amarelo. MP: 115.8 – 120.6°C. 1H NMR (300
MHz, CDCl3): δ 8.05 (d, J = 8.6 Hz, 1H), 7.33 – 7.27 (m, 2H), 6.99 (d, J = 7.9 Hz, 2H), 6.90 (t, J =
7.3 Hz, 1H), 6.72 (d, J = 8.6 Hz, 1H), 4.39 (q, J = 7.1 Hz, 2H), 3.97 (dt, J = 13.9, 7.0 Hz, 1H), 3.80
– 3.72 (m, 4H), 3.36 – 3.29 (m, 4H), 1.43 (t, J = 7.1 Hz, 3H), 1.37 (d, J = 7.0 Hz, 6H).13C NMR (75
MHz, CDCl3): δ 167.54, 164.26, 160.14, 156.82, 151.32, 132.78, 129.34, 120.31, 116.56, 108.71,
106.67, 104.60, 60.41, 49.29, 45.92, 29.83, 27.48, 20.79, 14.52. HRMS (ESI): m/z calcd [M + H]+:
for C23H28N3O3+ 394.2125, found 394.2122. (Hex/Acto 9:1)
Shai288: 32% yield (41 mg, 0.10 mmol) Sólido branco. MP: 203.0 – 205.9°C. 1H NMR (300 MHz,
CDCl3): δ 8.05 (d, J = 8.6 Hz, 1H), 7.23 (d, J = 8.9 Hz, 2H), 6.89 (d, J = 9.0 Hz, 2H), 6.71 (d, J =
8.6 Hz, 1H), 4.38 (q, J = 7.1 Hz, 2H), 3.96 (dt, J = 13.8, 6.9 Hz, 1H), 3.80 – 3.70 (m, 4H), 3.33 –
3.22 (m, 4H), 1.43 (t, J = 7.1 Hz, 3H), 1.36 (d, J = 7.0 Hz, 6H).13C NMR (75 MHz, CDCl3): δ
167.62, 164.25, 160.12, 156.71, 149.95, 132.83, 129.19, 125.14, 117.73, 108.85, 106.69, 104.62,
60.44, 49.26, 45.82, 29.84, 27.50, 20.80, 14.53.HRMS (ESI): m/z calcd [M + H]+: for
C23H27ClN3O3+ 428.1735, found 428.1734. (Hex/Acto 9:1)
Shai289b: 29% yield (27mg, 0.08 mmol) Óleo amarelo claro. 1H NMR (300 MHz, CDCl3):
xxxxxxxxxxxxx 13C NMR (75 MHz, CDCl3): xxxxxxxxxxxxxxxxxxxxx. HRMS (ESI): m/z calcd
[M + H]+: for C16H22NO3S+ 308.1315, found 308.1323. (Hex100%)
Shai289c: 26% yield (24 mg, 0.08 mmol) Óleo transparente. 1H NMR (300 MHz, CDCl3): δ 8.31
(d, J = 2.1 Hz, 1H), 8.29 (d, J = 2.2 Hz, 1H), 4.42 (q, J = 7.1 Hz, 2H), 4.02 (dt, J = 13.9, 6.9 Hz,
1H), 2.89 (t, J = 7.3 Hz, 2H), 1.45 (t, J = 7.1 Hz, 3H), 1.39 (d, J = 7.0 Hz, 6H), 1.01 (t, J = 7.3 Hz,
3H). 13C NMR (75 MHz, CDCl 3): δ 172.07, 163.61, 159.71, 146.63, 134.08, 129.37, 119.32,
106.35, 60.81, 38.09, 29.85, 27.80, 22.72, 20.59, 14.53, 13.37. HRMS (ESI): m/z calcd [M + H]+:
for C16H22NO3S+ 308.1315, found 308.1313. (Hex 100%)
Shai298: 48% yield (42 mg, 0.14 mmol) Sólido Bege. MP: 96.9 – 99.1°C. 1H NMR (300 MHz,
CDCl3): δ 8.01 (d, J = 8.6 Hz, 1H), 6.63 (d, J = 8.6 Hz, 1H), 4.37 (q, J = 7.1 Hz, 2H), 3.87 – 3.79
(m, 4H), 3.58 – 3.49 (m, 4H), 2.71 (s, 3H), 1.41 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3): δ
164.27, 160.06, 159.58, 156.96, 132.46, 108.91, 108.65, 104.24, 66.76, 60.43, 46.12, 14.51, 14.24.
HRMS (ESI): m/z calcd [M + H]+: for C15H19N2O4+ 291.1339, found 291.1341. (Hex/Acto7:3)
Shai299a 47% yield (52 mg, 0.14 mmol) Sólido amarelo claro. MP:132.6 – 134.5°C. 1H NMR (300
MHz, CDCl3): δ 8.03 (d, J = 8.6 Hz, 1H), 7.34 – 7.26 (m, 2H), 6.99 (d, J = 7.9 Hz, 2H), 6.90 (t, J =
7.3 Hz, 1H), 6.71 (d, J = 8.6 Hz, 1H), 4.38 (q, J = 7.1 Hz, 2H), 3.79 – 3.71 (m, 4H), 3.37 – 3.27 (m,
4H), 2.73 (s, 3H), 1.43 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3: δ 164.32, 160.13, 159.48,
156.77, 151.31, 132.48, 129.23, 120.26, 116.51, 108.68, 108.63, 104.53, 60.43, 49.22, 45.84,
14.53, 14.26. HRMS (ESI): m/z calcd: [M + H]+ for C21H24N3O3+ 366.1812, found 366.1813.
(Hex/Acto 9:1)
Shai311C 40% yield (52 mg, 0.12mmol) Sólido amarelo. MP: 73.1 – 78.3°C. 1H NMR (300 MHz,
CDCl3): δ 8.09 (d, J = 5.6 Hz,1H), 6.68 (d, J = 5.7 Hz, 1H), 4.36 (q, J = 7.1 Hz, 2H), 3.90 – 3.83
(m, 4H), 3.63 (dt, J = 13.9, 6.9 Hz, 1H), 3.16 – 3.08 (m, 4H), 1.38 (dd, J = 14.5, 7.1 Hz, 9H).. 13C
NMR (75 MHz, CDCl3): δ 165.92, 163.97, 162.42, 153.93, 145.11, 108.26, 107.99, 107.73, 77.16,
66.32, 61.26, 51.20, 27.81, 20.67, 14.40.. HRMS (ESI): m/z calcd: [M + H]+ for C23H27ClN3O3+
428.1735, found 428.1735. (Hex/Acto 5:5)
Shai312C 39% yield (35 mg, 0.09 mmol) Sólido amarelo. MP:87.9 – 90.3°C. 1H NMR (300 MHz,
CDCl3): δ 8.11 (d, J = 5.6 Hz, 1H), 7.29 (dd, J = 8.6, 7.4 Hz, 2H), 6.98 (d, J = 7.9 Hz, 2H), 6.90 (t,
J = 7.3 Hz, 1H), 6.74 (d, J = 5.7 Hz, 1H), 4.38 (q, J = 7.1 Hz, 2H), 3.66 (dd, J = 13.9, 6.9 Hz, 1H),
3.34 (q, J = 5.6 Hz, 8H), 1.43 – 1.36 (m, 9H). 13C NMR (75 MHz, CDCl 3): δ 165.75, 164.06,
162.47, 153.88, 151.24, 145.11, 129.31, 120.38, 116.57, 108.38, 108.12, 77.16, 61.34, 50.86, 48.88,
27.81, 20.94, 14.47. HRMS (ESI): m/z calcd [M + H]+: for C23H28N3O3+ 394.2125, found 394.2127.
(Hex/Acto 5:5)
Shai313C 40% yield (52 mg, 0.12 mmol) Sólido amarelo. MP:148.0 – 152.6°C. 1H NMR (300
MHz, CDCl3): δ 8.11 (d, J = 5.6 Hz, 1H), 7.22 (d, J = 9.0 Hz, 2H), 6.87 (d, J = 9.0 Hz, 2H), 6.73
(d, J = 5.7 Hz, 1H), 4.37 (q, J = 7.1 Hz, 2H), 3.64 (dt, J = 13.9, 6.9 Hz, 1H), 3.30 (s, 8H), 1.42 –
1.35 (m, 9H).13C NMR (75 MHz, CDCl 3): δ 165.90, 164.00, 162.46, 153.77, 149.85, 145.15,
129.14, 125.14, 117.72, 108.45, 108.11, 108.05, 77.16, 61.32, 50.74, 48.84, 27.85, 20.93,
14.47.HRMS (ESI): m/z calcd: [M + H]+ for C23H27ClN3O3+ 428.1735, found 428.1735. (Hex/Acto
5:5)
Shai326B 44% yield (49 mg, 0.13mmol) Sólido Bege. MP:92.6 – 95.9°C. 1H NMR (300 MHz,
CDCl3): δ 8.11 (d, J = 4.6 Hz, 1H), 7.30 (t, J = 7.1 Hz, 2H), 6.99 (d, J = 8.0 Hz, 2H), 6.91 (t, J =
6.9 Hz, 1H), 6.75 (d, J = 5.3 Hz, 1H), 4.38 (q, J = 6.9 Hz, 2H), 3.35 (d, J = 7.3 Hz, 8H), 2.69 (s,
3H), 1.40 (t, J = 7.0 Hz, 3H).13C NMR (75 MHz, CDCl3): δ 163.87, 162.56, 158.92, 153.88,
151.17, 145.24, 129.35, 116.66, 110.09, 108.20, 77.16, 61.28, 50.89, 48.97, 14.63, 14.57. HRMS
(ESI): m/z calcd: [M + H]+ for C21H24N3O3+ 366.1812, found 366.1813. (Hex/Acto 5:5)
Shai316B 37% yield (32mg, 0.11mmol) Óleo amarelo. 1H NMR (300 MHz, CDCl 3):
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxcccccccccc13C NMR (75 MHz, CDCl 3): δ

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xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx HRMS (ESI): m/z calcd [M + H]+: for
C15H19N2O4+ 291.1339, found 291.1339. (Hex/Acto 5:5)
Shai319 94% yield (100mg, 0.40 mmol) Sólido amarelo claro. MP:278.8 – 284.0°C. 1H NMR (300
MHz, CDCl3): δ 8.00 (d, J = 8.5 Hz, 1H), 6.37 (d, J = 8.6 Hz, 1H), 3.50 (dd, J = 8.0, 5.1 Hz, 4H),
2.74 (s, 3H), 2.06 – 2.00 (m, 4H). 13C NMR (75 MHz, CDCl 3): δ 160.86, 159.76, 155.15, 131.98,
106.07, 104.34, 77.16, 47.18, 25.66, 14.41.. HRMS (ESI): m/z calcd [M + H]+ for C13H15N2O3+
247.1077, found 247.1075. (Acto/MeOH 9.5:0.5)
Shai320 87% yield (182 mg, 0.66mmol) Sólido amarelo claro. MP:216.0 – 234.5°C. 1H NMR (300
MHz, CDCl3): δ 8.03 (d, J = 8.5 Hz, 1H), 6.37 (d, J = 8.6 Hz, 1H), 3.99 (dt, J = 13.7, 6.9 Hz, 1H),
3.51 (t, J = 6.3 Hz, 4H), 2.03 (t, J = 6.4 Hz, 4H), 1.38 (d, J = 6.9 Hz, 6H).13C NMR (75 MHz,
CDCl3): δ 170.05, 167.82, 160.85, 155.17, 132.29, 106.11, 104.40, 77.16, 47.25, 27.56, 25.66,
20.88. HRMS (ESI): m/z calcd [M + H]+ for C15H19N2O3+ 275.1390, found 275.1396. (Hex/Acto
5:5)
Shai321 44% yield ( 24mg, 0.08 mmol) Sólido branco. MP:171.1 – 173.4°C. 1H NMR (300 MHz,
CDCl3): δ 7.67 (d, J = 8.5 Hz, 1H), 6.29 (d, J = 8.5 Hz, 1H), 5.82 (s, 1H), 3.74 (dt, J = 13.8, 6.9 Hz,
1H), 3.47 (t, J = 6.6 Hz, 4H), 3.00 (d, J = 4.9 Hz, 3H), 2.05 – 1.93 (m, 4H), 1.33 (d, J = 6.9 Hz,
6H).13C NMR (75 MHz, CDCl3): δ 164.95, 161.72, 160.75, 154.81, 129.85, 109.64, 105.64, 103.57,
77.16, 47.19, 27.27, 26.49, 25.60, 21.19. HRMS (ESI): ): m/z calcd [M + H]+ for C16H22N3O2+
288.1707, found 288.1707. (Hex/Acto 7:3)
Shai324 55% yield (17 mg, 0.06 mmol) Sólido amarelo claro. MP:150.0 – 160.5°C. 1H NMR (300
MHz, CDCl3): δ 7.69 (d, J = 8.5 Hz, 1H), 6.30 (d, J = 8.5 Hz, 1H), 5.83 (s, 1H), 3.47 (t, J = 6.6 Hz,
4H), 3.01 (d, J = 4.9 Hz, 3H), 2.62 (s, 3H), 2.07 – 1.94 (m, 4H).13C NMR (75 MHz, CDCl 3): δ
165.13, 160.69, 154.77, 153.74, 129.80, 111.52, 105.59, 103.63, 77.16, 47.15, 26.55, 25.63, 13.85.
HRMS (ESI): m/z calcd [M + H]+ for C14H18N3O2+ 260.1394, found 260.1395. (Hex/Acto 6:4)

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Figura 1. Shai273

Figura 2. shai273

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Figura 3. Shai276

Figura 4shai279a

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Figura 5 shai284

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Figura 6 shai279a

Figura 7. shai279b

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Figura 8. shai279b

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Figura 9. shai284

Figura 10. shai287

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Figura 11. shai287

Figura 12. shai288

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Figura 13. shai288

Figura 14. shai289c

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Figura 15. shai289c

Figura 16. shai299a

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Figura 17. shai299a

Figura 18. shai298

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Figura 19. shai298

Figura 20. shai311c

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Figura 21. Shai311c

Figura 22shai312c

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Figura 23. shai312c

Figura 24. shai313c

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Figura 25. shai313c

Figura 26. shai326B

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Figura 27. shai326B

Figura 28. shai319

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Figura 29. shai319

Figura 30. shai320

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Figura 31. shai320

Figura 32. shai321

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Figura 33. shai321

Figura 34. shai324

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Figura 35. shai324

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