7674
Q. Yue et al. / Tetrahedron 71 (2015) 7670e7675
4.2.9.3. Compound 10c. White solid. Yield 93%, mp 161e162 ꢀC.
1H NMR (CDCl3, 400 MHz)
: 1.23e1.39 (m, 3H), 1.46e1.55 (m, 2H),
solution was extracted with ethyl acetate (10 mL ꢂ3). The com-
d
bined organic layer was washed with saturated aqueous sodium
chloride (10 mL ꢂ3), dried over sodium sulfate, filtered and con-
centrated in vacuo. The residue was purified by silica gel column
chromatography to give 12. (0.74 g, 95%) as a white solid, mp
1.68e1.71 (m, 1H), 1.77e1.81 (m, 2H), 2.18e2.21 (m, 2H), 4.43 (s, 1H,
CH), 5.09 (br, 1H, NH), 7.65 (d, 1H, J¼8.8 Hz), 8.65 (d, 1H, J¼8.8 Hz),
8.72 (s, 1H). 13C NMR (CDCl3, 100 MHz)
d: 163.11(1C), 156.55(1C),
146.29(1C), 142.20(1C), 130.85(2C), 130.36(2C), 123.22(1C),
49.14(1C), 32.95(2C), 25.69(1C), 23.89(2C). ESI-HRMS: calcd for
209e211 ꢀC. 1H NMR (CDCl3, 400 MHz)
d
: 3.57 (t, 4H, J¼4.8 Hz,
OeCH2 ꢂ2), 3.75 (t, 4H, J¼4.8 Hz, OeCH2 ꢂ2), 3.87e3.90 (m, 8H,
NeCH2 ꢂ2), 7.07 (d, 1H, J¼10.0 Hz), 8.49 (d, 1H, J¼10.0 Hz), 8.83 (s,
C
15H15ClF3N5þNaþ 380.0866, found 380.0865. Elemental Analysis:
C, 50.36; H, 4.23; Cl, 9.91; F, 15.93; N, 19.58, found C, 50.24; H, 4.15;
Cl, 10.03; F, 15.87; N, 19.65.
1H). 13C NMR (CDCl3, 100 MHz)
d: 162.57(1C), 158.20(1C),
149.47(1C), 142.10(1C), 130.93(2C), 130.48(2C), 121.83(1C),
66.38(4C),
C
49.84(2C),
49.01(2C).
ESI-HRMS:
calcd
for
4.2.9.4. Compound 10d. Yellow solid. Yield 70%, mp 213e215 ꢀC.
17H19F3N6O2þNaþ 419.1419, found 419.1417. Elemental Analysis: C,
1H NMR (CDCl3, 400 MHz)
d
: 2.41 (s, 3H, CH3), 2.66 (s, 4H, CH2 ꢂ2),
3.75 (s, 4H, NeCH2 ꢂ2), 7.68 (d, 1H, J¼8.8 Hz), 8.69 (d, 1H, J¼8.8 Hz),
8.82 (s, 1H). 13C NMR (CDCl3, 100 MHz)
: 165.42(1C), 155.35(1C),
148.69(1C), 143.16(1C), 132.61(2C), 132.01(2C), 120.00(1C),
51.51; H, 4.83; F, 14.38; N, 21.20, found C, 51.55; H, 4.80; F, 14.34; N,
21.26.
d
4.2.11. Synthesis of compound 11aeh. To a solution of acetic acid
(10 mL) was added compound 10aeh (2.0 mmol). After stirring for
2 h at 100 ꢀC, the mixture was concentrated under reduced pres-
sure, and the residue was purified by silica gel column chroma-
tography to give 11aeh.
55.04(2C),
49.51(2C),
30.33(1C).
ESI-HRMS:
calcd
for
C
14H14ClF3N6þNaþ 381.0818, found 381.0815. Elemental Analysis:
C, 46.87; H, 3.93; Cl, 9.88; F, 15.89; N, 23.43, found C, 46.95; H, 3.86;
Cl, 9.91; F, 15.94; N, 23.37.
4.2.9.5. Compound 10e. Yellow solid. Yield 78%, mp 149e151 ꢀC.
4.2.11.1. Compound 11a. Yellow solid. Yield 91%, mp
1H NMR (CDCl3, 400 MHz)
d
: 2.06e2.09 (m, 4H, CH2 ꢂ2), 3.84 (s, 4H,
NeCH2 ꢂ2), 7.63 (d, 1H, J¼9.2 Hz), 8.66 (d, 1H, J¼9.2 Hz), 8.78 (s,
1H). 13C NMR (CDCl3, 100 MHz)
160.87(1C), 152.61(1C),
242e244 ꢀC. 1H NMR (CDCl3, 400 MHz)
d
: 3.63 (t, 4H, J¼4.2 Hz,
OeCH2 ꢂ2), 3.89 (t, 4H, J¼4.2 Hz, NeCH2 ꢂ2), 7.17 (d, 1H, J¼9.6 Hz),
d
:
8.40 (s, 1H), 8.58 (d, 1H, J¼9.6 Hz), 12.71 (br, 1H, OH). 13C NMR
146.67(1C), 143.36(1C), 129.73(2C), 129.17(2C), 122.65(1C),
(CDCl3, 100 MHz) d: 162.37(1C), 157.26(1C), 149.19(1C), 142.16(1C),
49.31(2C), 25.65(2C). ESI-HRMS: calcd for
C
13H11ClF3N5þNaþ
130.89(2C), 130.36(2C), 124.51(1C), 66.59(2C), 50.60(2C). ESI-
HRMS: calcd for C13H12F3N5O2þNaþ 350.0841, found 350.0840.
Elemental Analysis: C, 47.71; H, 3.70; F, 17.42; N, 21.40, found C,
47.66; H, 3.78; F, 17.35; N, 21.44.
352.0553, found 352.0556. Elemental Analysis: C, 47.36; H, 3.36; Cl,
10.75; F, 17.29; N, 21.24, found C, 47.41; H, 3.39; Cl, 10.68; F, 17.34; N,
21.29.
4.2.9.6. Compound 10f. White solid. Yield 88%, mp 168e170 ꢀC.
4.2.11.2. Compound 11b. Yellow solid. Yield 90%, mp
1H NMR (CDCl3, 400 MHz)
d
: 1.02 (d, 3H, J¼6.4 Hz, CH3), 1.36e1.45
238e240 ꢀC. 1H NMR (CDCl3, 600 MHz)
d: 1.72e1.75 (m, 6H, CH2
(m, 3H, CH2þCH), 1.81 (d, 1H, J¼13.2 Hz, CH2), 3.17 (t, 2H,
J¼12.0 Hz), 4.13 (d, 2H, J¼13.2 Hz, NeCH2), 7.66 (d, 1H, J¼9.2 Hz),
ꢂ3), 3.54e3.57 (m, 4H, NeCH2 ꢂ2), 7.13 (d, 1H, J¼10.0 Hz), 8.31 (s,
1H), 8.57 (d, 1H, J¼10.0 Hz), 12.41 (s, 1H). 13C NMR (CDCl3, 150 MHz)
8.68 (d, 1H, J¼9.2 Hz), 8.78 (s, 1H). 13C NMR (CDCl3, 100 MHz)
d:
d: 162.37(1C), 157.95(1C), 148.31(1C), 142.50(1C), 130.84(2C),
160.30(1C), 153.73(1C), 147.26(1C), 141.52(1C), 128.83(2C),
128.08(2C), 121.67(1C), 49.98(2C), 33.55(2C), 23.27(1C), 19.92(1C).
ESI-HRMS: calcd for C15H15ClF3N5þNaþ 380.0866, found 380.0869.
Elemental Analysis: C, 50.36; H, 4.23; Cl, 9.91; F, 15.93; N, 19.58,
found C, 50.42; H, 4.18; Cl, 9.82; F, 16.02; N, 19.63.
130.33(2C), 123.99(1C), 51.31(2C), 25.72(2C), 24.12(1C). ESI-HRMS:
calcd for C14H14F3N5OþNaþ 348.1048, found 348.1046. Elemental
Analysis: C, 51.69; H, 4.34; F, 17.52; N, 21.53, found C, 51.52; H, 4.28;
F, 17.63; N, 21.59.
4.2.11.3. Compound 11c. Yellow solid. Yield 90%, mp
4.2.9.7. Compound 10g. Yellow solid. Yield 74%, mp 129e131 ꢀC.
263e264 ꢀC. 1H NMR (CDCl3, 400 MHz)
d: 1.24e1.34 (m, 3H),
1H NMR (CDCl3, 400 MHz)
d
: 3.35 (s, 6H, NeCH3 ꢂ2), 7.66 (d, 1H,
1.43e1.52 (m, 2H), 1.66e1.69 (m, 1H), 1.76e1.79 (m, 2H), 2.15e2.18
(m, 2H), 4.36 (d, 1H, J¼6.8 Hz, NeCH), 4.95 (d, 1H, J¼6.8 Hz, NH),
7.11 (d, 1H, J¼9.6 Hz), 8.21 (s, 1H), 8.54 (d, 1H, J¼9.6 Hz), 12.41 (s, 1H,
J¼9.2 Hz), 8.67 (d, 1H, J¼9.2 Hz), 8.80 (s, 1H). 13C NMR (CDCl3,
100 MHz)
d: 162.35(1C), 157.25(1C), 149.18(1C), 142.15(1C),
130.88(2C), 130.35(2C), 124.50(1C), 42.23(2C). ESI-HRMS: calcd for
OH). 13C NMR (CDCl3, 100 MHz)
d: 162.74(1C), 157.63(1C),
C
11H9ClF3N5þNaþ 326.0396, found 326.0397. Elemental Analysis: C,
146.24(1C), 142.75(1C), 130.75(2C), 130.17(2C), 122.03(1C),
50.55(1C), 32.69(2C), 25.53(1C), 24.63(2C). ESI-HRMS: calcd for
43.51; H, 2.99; Cl, 11.67; F, 18.77; N, 23.06, found C, 43.46; H, 2.87;
Cl, 11.77; F, 18.86; N, 22.99.
C
15H16F3N5OþNaþ 362.1205, found 362.1209. Elemental Analysis:
C, 53.10; H, 4.75; F, 16.80; N, 20.64, found C, 53.04; H, 4.71; F, 16.83;
N, 20.69.
4.2.9.8. Compound 10h. Yellow solid. Yield 67%, mp 136e138 ꢀC.
1H NMR (CDCl3, 400 MHz)
d
: 1.04 (t, 3H, J¼7.2 Hz, CH3), 1.74e1.83
(m, 2H, CH2), 3.75 (q, 2H, J¼6.0 Hz, NeCH2), 5.26 (br, 1H, NH), 7.64
4.2.11.4. Compound 11d. Yellow solid. Yield 93%, mp
(d,1H, J¼8.8 Hz), 8.65 (d,1H, J¼8.8 Hz), 8.71 (s,1H). 13C NMR (CDCl3,
290e292 ꢀC. 1H NMR (DMSO-d6, 400 MHz)
d: 2.61 (s, 3H, CH3), 3.04
100 MHz)
d:
161.54(1C), 152.21(1C), 147.04(1C), 142.41(1C),
(s, 4H, CH2 ꢂ2), 3.58 (s, 4H, CH2 ꢂ2), 7.11 (d, 1H, J¼8.8 Hz), 8.25 (s,
131.32(2C), 130.80(2C), 122.35(1C), 44.05(1C), 22.71(1C), 13.01(1C).
ESI-HRMS: calcd for C12H11ClF3N5þNaþ 340.0553, found 340.0551.
Elemental Analysis: C, 45.37; H, 3.49; Cl, 11.16; F, 17.94; N, 22.04,
found C, 45.31; H, 3.53; Cl, 11.22; F, 17.87; N, 22.11.
1H), 8.37 (d, 1H, J¼8.8 Hz), 13.54 (br, 1H, OH). 13C NMR (CDCl3,
150 MHz)
d: 162.37(1C), 157.25(1C), 149.19(1C), 142.15(1C),
130.88(2C), 130.37(2C), 124.50(1C), 57.20(2C), 50.67(2C), 29.66(1C).
ESI-HRMS: calcd for C14H15F3N6OþNaþ 363.1157, found 363.1156.
Elemental Analysis: C, 49.41; H, 4.44; F, 16.75; N, 24.70, found C,
49.46; H, 4.38; F, 16.81; N, 24.74.
4.2.10. Synthesis of compound 12. To a solution of 9 (0.58 g,
2.0 mmol) in DMF (10 mL) was added morpholine (0.86 g,
10 mmol). The resulting mixture was stirred at 80 ꢀC for 0.5 h, and
ethyl acetate (10 mL) and water (10 mL) were added. After stirring
for 10 min, the organic solution was separated and the aqueous
4.2.11.5. Compound 11e. Yellow solid. Yield 91%, mp
260e262 ꢀC. 1H NMR (DMSO-d6, 400 MHz)
3.67 (s, 4H, Ne CH2 ꢂ2), 7.07 (d, 1H, J¼9.2 Hz), 8.10 (s, 1H), 8.35 (d,
d
: 1.98 (s, 4H, CH2 ꢂ2),