8.14 (ddd, J = 7.9, 1.8, 1.2 Hz, 1H), 8.11 (s, 1H), 8.01 (ddd, J = 7.7, 1.7, 1.2 Hz, 1H), 7.79 (ddd, J = 7.8, 1.6, 0.9 Hz, 1H), 7.75 – 7.66
(
2
m, 2H), 7.47 (td, J = 8.0, 6.1 Hz, 1H), 7.16 (dddd, J = 9.0, 8.2, 2.7, 0.9 Hz, 1H), 3.70 (td, J = 6.8, 5.5 Hz, 2H), 3.32 (t, J = 6.39 Hz,
H); EIMS m/z 352.1 (M + 1) ; HPLC 100 area% (254 nm). Anal. Calcd for C19H14FN OS: C, 64.94 H, 4.02; N, 11.96. Found: C,
3
+
64.75; H, 4.19; N, 11.83.
5
.2.5.5. 2-[2-(3-Cyanobenzamido)]ethyl-4-(4-fluorophenyl)thiazole (58) was prepared from 89d and 3-cyanobenzoyl chloride as
1
6
white crystals (68 mg, 19%): mp 126-128 °C; H NMR (400 MHz, DMSO-d ) δ 8.90 (t, J = 5.6 Hz, 1H), 8.24 (t, J = 1.8 Hz, 1H), 8.14
(
6
1
ddd, J = 7.9, 1.9, 1.2 Hz, 1H), 8.05 – 7.93 (m, 4H), 7.70 (t, J = 7.9 Hz, 1H), 7.33 – 7.18 (m, 2H), 3.70 (q, J = 6.8 Hz, 2H), 3.31 (t, J =
+
.8 Hz, 2H); EIMS m/z 352.1 (M + 1) ; HPLC 100 area% (254 nm). Anal. Calcd for C19
H14FN
3 2
OS·0.2H O: C, 64.28 H, 4.09; N,
1.84. Found: C, 64.21; H, 4.11; N, 11.66.
5
.2.5.6. 2-[2-(3-Nitrobenzamido)]ethyl-4-(2-fluorophenyl)thiazole (59) was prepared from 89b and 3-nitrobenzoyl chloride as
1
white crystals (276 mg, 74%): mp 114-115 °C; H NMR (400 MHz, DMSO-d
6
) δ 9.09 (t, J = 5.6 Hz, 1H), 8.70 – 8.64 (m, 1H), 8.39
(ddd, J = 8.3, 2.4, 1.0 Hz, 1H), 8.28 (dt, J = 7.8, 1.4 Hz, 1H), 8.10 (td, J = 7.9, 1.9 Hz, 1H), 7.87 (d, J = 2.5 Hz, 1H), 7.79 (t, J = 8.0 Hz,
1
3
1
H), 7.39 (dddd, J = 8.8, 7.2, 5.2, 1.8 Hz, 1H), 7.35 – 7.22 (m, 2H), 3.73 (td, J = 6.8, 5.5 Hz, 2H), 3.35 (t, J = 6.8 Hz, 2H); EIMS m/z
+
72.1 (M + 1) ; HPLC 100 area% (254 nm). Anal. Calcd for C18
1.27.
3 3
H14FN O S: C, 58.21 H, 3.80; N, 11.31. Found: C, 58.18; H, 3.85; N,
5
.2.5.7. 2-[2-(3-Nitrobenzamido)]ethyl-4-(3-fluorophenyl)thiazole (60) was prepared from 89c and 3-nitrobenzoyl chloride as
1
white crystals (301 mg, 81%): mp 106 °C; H NMR (400 MHz, DMSO-d
6
) δ 9.08 (t, J = 5.6 Hz, 1H), 8.67 (t, J = 2.0 Hz, 1H), 8.39
(ddd, J = 8.2, 2.3, 1.1 Hz, 1H), 8.28 (ddd, J = 7.8, 1.7, 1.0 Hz, 1H), 8.11 (s, 1H), 7.83 – 7.73 (m, 2H), 7.72 (ddd, J = 10.7, 2.6, 1.5 Hz,
1
3
H), 7.46 (td, J = 8.0, 6.1 Hz, 1H), 7.16 (dddd, J = 9.1, 8.3, 2.7, 1.0 Hz, 1H), 3.73 (q, J = 6.9, 2H), 3.34 (t, J = 6.9 Hz, 2H); EIMS m/z
+
3 3 2
72.1 (M + 1) ; HPLC 98.6 area% (254 nm). Anal. Calcd for C18H14FN O S·0.25H O: C, 57.51 H, 3.89; N, 11.18. Found: C, 57.32;
H, 3.71; N, 11.05.
5
.2.5.8. 2-[2-(3-Nitrobenzamido)]ethyl-4-(4-fluorophenyl)thiazole (61) was prepared from 89d and 3-nitrobenzoyl chloride as
1
white crystals (261 mg, 70%): mp 143-144 °C; H NMR (400 MHz, DMSO-d
6
) δ 9.08 (t, J = 5.6 Hz, 1H), 8.67 (ddd, J = 2.3, 1.7, 0.5
Hz, 1H), 8.39 (ddd, J = 8.2, 2.3, 1.0 Hz, 1H), 8.28 (ddd, J = 7.8, 1.7, 1.1 Hz, 1H), 8.05 – 7.93 (m, 3H), 7.79 (dd, J = 8.3, 7.7 Hz, 1H),
+
7
.32 – 7.17 (m, 2H), 3.72 (td, J = 6.9, 5.5 Hz, 2H), 3.33 (d, J = 6.8 Hz, 2H); EIMS m/z 372.1 (M + 1) ; HPLC 100 area% (254 nm).
Anal. Calcd for C18 S: C, 58.21 H, 3.80; N, 11.31. Found: C, 58.35; H, 3.93; N, 11.17.
3 3
H14FN O
5
.2.5.9. 2-[2-(3-Fluorobenzamido)]ethyl-4-(3-fluorophenyl)thiazole (62) was prepared from 89c and 3-fluorobenzoyl chloride as
1
white crystals (266 mg, 77%): mp 106-107 °C; H NMR (400 MHz, DMSO-d
.8, 1.6, 0.9 Hz, 1H), 7.74 (ddd, J = 10.7, 2.7, 1.5 Hz, 1H), 7.69 (dt, J = 7.7, 1.2 Hz, 1H), 7.62 (ddd, J = 10.1, 2.7, 1.5 Hz, 1H), 7.50
dtd, J = 22.2, 8.0, 6.0 Hz, 2H), 7.39 (tdd, J = 8.3, 2.6, 1.0 Hz, 1H), 7.16 (dddd, J = 9.0, 8.2, 2.7, 0.9 Hz, 1H), 3.68 (td, J = 6.8, 5.5 Hz,
6
) δ 8.78 (t, J = 5.6 Hz, 1H), 8.10 (s, 1H), 7.80 (ddd, J =
7
(
2
+
H), 3.31 (t, J = 6.9 Hz, 2H); EIMS m/z 345.2 (M + 1) ; HPLC 100 area% (254 nm). Anal. Calcd for C18
14 2 2
H F N OS: C, 62.78 H, 4.10;
N, 8.13. Found: C, 62.59; H, 4.16; N, 8.03.
5
.2.5.10. 2-[2-(3-Fluorobenzamido)]ethyl-4-(4-fluorophenyl)thiazole (63)was prepared from 89d and 3-fluorobenzoyl chloride as
1
white crystals (266 mg, 77%): mp 122 °C; H NMR (400 MHz, DMSO-d
6
) δ 8.78 (t, J = 5.6 Hz, 1H), 7.99 (dd, J = 8.9, 5.6 Hz, 2H),
7
1
.96 (s, 1H), 7.69 (dt, J = 7.8, 1.2 Hz, 1H), 7.62 (ddd, J = 10.1, 2.7, 1.5 Hz, 1H), 7.53 (td, J = 8.0, 5.8 Hz, 1H), 7.39 (tdd, J = 8.4, 2.7,
+
.0 Hz, 1H), 7.30 – 7.21 (m, 2H), 3.68 (td, J = 6.9, 5.6 Hz, 2H), 3.30 (t, J = 7.0 Hz, 2H); EIMS m/z 345.2 (M + 1) ; HPLC 100 area%
OS: C, 62.78 H, 4.10; N, 8.13. Found: C, 62.72; H, 4.17; N, 8.06.
(254 nm). Anal. Calcd for C18
14 2 2
H F N
5
.2.5.11. 2-(2-Thiophen-2-ylamido)ethyl-4-(2-fluorophenyl)thiazole (64) was prepared from 89b and thiophene-2-carbonyl
1
chloride as white crystals (267 mg, 80%): mp 139-141 °C; H NMR (400 MHz, DMSO-d
6
) δ 8.70 (t, J = 5.7 Hz, 1H), 8.12 (td, J = 7.9,
1
2
.9 Hz, 1H), 7.86 (d, J = 2.6 Hz, 1H), 7.75 (dd, J = 5.0, 1.1 Hz, 1H), 7.73 (dd, J = 3.7, 1.2 Hz, 1H), 7.45 – 7.37 (m, 1H), 7.36 – 7.24 (m,
+
H), 7.15 (dd, J = 5.0, 3.7 Hz, 1H), 3.66 (td, J = 6.9, 5.6 Hz, 2H), 3.31 (t, J = 6.9 Hz, 2H); EIMS m/z 333.1 (M + 1) ; HPLC 100 area%
OS : C, 57.81 H, 3.94; N, 8.43. Found: C, 57.72; H, 4.06; N, 8.37.
(254 nm). Anal. Calcd for C16
H13FN
2
2
5
.2.5.12. 2-(2-Thiophen-2-ylamido)ethyl-4-(3-fluorophenyl)thiazole (65) was prepared from 89c and thiophene-2-carbonyl
1
chloride as ivory needles (266 mg, 79%): mp 137-138 °C; H NMR (400 MHz, DMSO-d
6
) δ 8.70 (t, J = 5.7 Hz, 1H), 8.10 (d, J = 0.6
Hz, 1H), 7.84 – 7.77 (m, 1H), 7.77 – 7.69 (m, 3H), 7.47 (td, J = 8.0, 6.1 Hz, 1H), 7.17 (ddd, J = 8.1, 2.7, 0.8 Hz, 1H), 7.16 – 7.11 (m,
+
1
H), 3.65 (q, J = 6.6 Hz, 2H), 3.30 (t, J = 6.9 Hz, 2H); EIMS m/z 333.2 (M + 1) ; HPLC 98.9 area% (265 nm). Anal. Calcd for
C
16
H13FN
2
OS : C, 57.81 H, 3.94; N, 8.43. Found: C, 57.68; H, 3.97; N, 8.31.
2
5
.2.5.13. 2-(2-Thiophen-2-ylamido)ethyl-4-(4-fluorophenyl)thiazole (66) was prepared from 89d and thiophene-2-carbonyl
1
chloride as a white solid (268 mg, 80%): mp 124-125 °C; H NMR (400 MHz, DMSO-d
6
) δ 8.70 (t, J = 5.7 Hz, 1H), 8.03 – 7.96 (m,
2
H), 7.96 (s, 1H), 7.75 (dd, J = 5.0, 1.1 Hz, 1H), 7.72 (dd, J = 3.8, 1.2 Hz, 1H), 7.31 – 7.18 (m, 2H), 7.14 (dd, J = 5.0, 3.7 Hz, 1H), 3.65
+
(td, J = 6.9, 5.6 Hz, 2H), 3.29 (t, J = 7.0 Hz, 2H); EIMS m/z 333.2 (M + 1) ; HPLC 100 area% (265 nm). Anal. Calcd for
C
16
H13FN
2
OS : C, 57.81 H, 3.94; N, 8.43. Found: C, 57.61; H, 4.03; N, 8.39.
2
5
.2.5.14. 2-(2-Pyrrolidin-1-ylamido)ethyl-4-(2-fluorophenyl)thiazole (67) was prepared from 89b and pyrrolidine-1-carbonyl
1
6
chloride as a white solid (111 mg, 34%): mp 102-103 °C; H NMR (400 MHz, DMSO-d ) δ 8.12 (td, J = 7.8, 1.7 Hz, 1H), 7.85 (d, J =
2
–
1
.6 Hz, 1H), 7.45 – 7.36 (m, 1H), 7.35 – 7.26 (m, 2H), 6.32 (t, J = 5.6 Hz, 1H), 3.42 (td, J = 7.0, 5.5 Hz, 2H), 3.25 – 3.14 (m, 6H), 1.84
+
1.73 (m, 4H); EIMS m/z 320.1 (M + 1) ; HPLC 99.1 area% (254 nm). Anal. Calcd for C16
H18FN
3 · 2
OS 0.2H O: C, 59.50; H, 5.74; N,
3.01. Found: C, 59.39; H, 5.71; N, 13.00.
5
.2.5.15. 2-(2-Pyrrolidin-1-ylamido)ethyl-4-(3-fluorophenyl)thiazole (68) was prepared from 89c and pyrrolidine-1-carbonyl
1
chloride as white crystals (256 mg, 80%): mp 118-120 °C; H NMR (400 MHz, DMSO-d
6
) δ 8.10 (s, 1H), 7.80 (ddd, J = 7.8, 1.6, 0.9
Hz, 1H), 7.75 (ddd, J = 10.7, 2.7, 1.5 Hz, 1H), 7.48 (td, J = 8.0, 6.2 Hz, 1H), 7.17 (dddd, J = 9.0, 8.3, 2.7, 0.9 Hz, 1H), 6.31 (t, J = 5.6