S. Q. Yao, C. Y. He et al.
146.7, 166.8, 173.8 ppm; LC-IT-TOF/MS: m/z calcd for C27H26N4O4:
471.1954 [M+H]+; found: 471.1968.
sodium acetate (108 mg, 1.3 mmol), and cyanogen bromide (141 mg,
1.3 mmol) in anhydrous methanol (10 mL) to afford 1h (97 mg, 67%) as
a white solid. 1H NMR (500 MHz, CDCl3): d=0.89 (t, J=10.0 Hz, 6H),
1.94–2.04 (m, 1H), 3.06–3.13 (m, 2H), 3.19 (s, 3H), 3.60–3.73 (m, 1H),
3.84–3.89 (m, 1H), 4.27–4.30 (m, 4H), 4.72 (t, J=10.0, 1H), 6.36 (d, J=
10.0 Hz, 1H), 6.89 (d, J=10 Hz, 1H), 7.23–7.38 ppm (m, 7H); 13C NMR
(126 MHz, CDCl3): d=17.9, 19.5, 31.0, 31.4, 32.9, 54.1, 54.8, 64.2, 64.6,
112.6, 116.6, 117.3, 120.5, 127.1, 127.2, 128.8, 129.2, 136.3, 143.4, 146.7,
166.9, 174.0 ppm; LC-IT-TOF/MS: m/z calcd for C24H28N4O4: 437.2111
[M+H]+; found: 437.2121.
(S)-N-[1-(2-Cyano-1-methyl-2-phenethylhydrazinyl)-1-oxo-3-phenylpro-
pan-2-yl]-2,3-dihydrobenzo[b]ACTHUNRTGNEUNG[1,4]dioxine-6-carboxamide (1c): Prepared
according to the general procedure using 12c (138 mg, 0.3 mmol), sodium
acetate (100 mg, 1.2 mmol), and cyanogen bromide (128 mg, 1.2 mmol) in
anhydrous methanol (10 mL) to afford 1c (118 mg, 81%) as a white
solid. 1H NMR (500 MHz, CDCl3): d=2.85–2.89 (m, 2H), 3.06–3.16 (m,
2H), 3.18 (s, 3H), 3.71–3.76 (m, 1H), 3.83–3.89 (m, 1H), 4.26 (dd, J=5.0,
10.0 Hz, 4H), 5.11–5.16 (m, 1H), 6.38 (d, J=10.0 Hz, 1H), 6.85 (d, J=
10.0 Hz, 1H), 7.03 (d, J=10.0 Hz, 1H), 7.15–7.36 ppm (m, 11H);
13C NMR (126 MHz, CDCl3): d=31.6, 32.9, 37.7, 50.6, 54.8, 64.2, 64.5,
112.3, 116.6, 117.3, 120.5, 126.9, 127.2, 127.3, 128.8, 128.9, 129.0, 129.2,
129.5, 135.4, 136.2, 143.4, 146.8, 166.6, 173.4 ppm; LC-IT-TOF/MS: m/z
calcd for C28H28N4O4: 485.2111 [M+H]+; found: 485.2102.
(S)-N-{1-[2-Cyano-1-methyl-2-(3-phenylpropyl)hydrazinyl]-3-methyl-1-
oxobutan-2-yl}-2,3-dihydrobenzo[b]ACTHNUTRGENUGN[1,4]dioxine-6-carboxamide (1i): Pre-
pared according to the general procedure using 12i (127 mg, 0.3 mmol),
sodium acetate (98 mg, 1.2 mmol), and cyanogen bromide (127 mg,
1.2 mmol) in anhydrous methanol (10 mL) to afford 1i (101 mg, 75%) as
a white solid. 1H NMR (500 MHz, CDCl3): d=1.02 (d, J=5.0 Hz, 3H),
1.08 (d, J=5.0 Hz, 3H), 2.09–2.18 (m, 3H), 2.78–2.85 (m, 2H), 3.21 (s,
3H), 3.43–3.51 (m, 2H), 4.26 (dd, J=5.0, 10.0 Hz, 4H), 5.18 (dd, J=5.0,
10.0 Hz, 1H), 6.54 (d, J=10.0 Hz, 1H), 6.89 (d, J=10 Hz, 1H), 7.19–
7.34 ppm (m, 7H); 13C NMR (126 MHz, CDCl3): d=17.8, 19.7, 28.1,
31.38, 31.42, 32.6, 53.6, 53.9, 64.2, 64.5, 113.7, 116.6, 117.3, 120.5, 126.3,
127.2, 128.3, 128.6, 140.1, 143.4, 146.7, 166.8, 174.0 ppm; LC-IT-TOF/MS:
m/z calcd for C25H30N4O4: 451.2267 [M+H]+; found: 451.2284.
(S)-N-{1-[2-Cyano-1-methyl-2-(3-phenylpropyl)hydrazinyl]-1-oxo-3-phe-
nylpropan-2-yl}-2,3-dihydrobenzo[b]
G
(1d):
Prepared according to the general procedure using 12d (160 mg,
0.34 mmol), sodium acetate (112 mg, 1.4 mmol), and cyanogen bromide
(143 mg, 1.4 mmol) in anhydrous methanol (10 mL) to afford 1d (123 mg,
73%) as a white solid. 1H NMR (500 MHz, CDCl3): d=2.10–2.16 (m,
2H), 2.74–2.86 (m, 2H), 3.00–3.04 (m, 2H), 3.22 (s, 3H), 3.45–3.55 (m,
2H), 4.26 (dd, J=5.0, 10.0 Hz, 4H), 5.44–5.48 (m, 1H), 6.63 (d, J=
10.0 Hz, 1H), 6.84 (d, J=10.0 Hz, 1H), 7.13–7.33 ppm (m, 11H);
13C NMR (126 MHz, CDCl3): d=28.2, 31.6, 32.6, 38.0, 50.8, 53.6, 64.2,
64.6, 112.5, 116.6, 117.3, 120.6, 126.4, 126.9, 127.4, 128.4, 128.7, 128.8,
129.2, 129.6, 135.7, 140.0, 143.4, 146.8, 166.6, 168.4, 173.5 ppm; LC-IT-
TOF/MS: m/z calcd for C29H30N4O4: 499.2267 [M+H]+; found: 499.2329.
(S)-N-[1-(2-Butyl-2-cyano-1-methylhydrazinyl)-3-methyl-1-oxobutan-2-
yl]-2,3-dihydrobenzo[b]ACTHNUTRGNEUG[N 1,4]dioxine-6-carboxamide (1j): Prepared ac-
cording to the general procedure using 12j (124 mg, 0.34 mmol), sodium
acetate (112 mg, 1.4 mmol), and cyanogen bromide (144 mg, 1.4 mmol) in
anhydrous methanol (10 mL) to afford 1j (94 mg, 71%) as a white solid.
1H NMR (500 MHz, CDCl3): d=1.02 (d, J=5.0 Hz, 3H), 1.08 (d, J=
5.0 Hz, 3H), 1.49–1.58 (m, 2H), 1.73–1.81 (m, 2H), 2.13–2.19 (m, 1H),
3.24 (s, 3H), 3.37–3.50 (m, 2H), 4.26–4.30 (m, 4H), 5.14 (dd, J=5.0,
10.0 Hz, 1H), 6.54 (d, J=5.0 Hz, 1H), 6.89 (d, J=10.0 Hz, 1H), 7.28–
7.34 ppm (m, 2H); 13C NMR (126 MHz, CDCl3): d=13.7, 17.6, 19.7, 19.8,
53.8, 54.0, 64.2, 64.5, 112.7, 116.6, 117.3, 120.5, 127.2, 143.4, 146.7, 166.8,
173.9 ppm; LC-IT-TOF/MS: m/z calcd for C20H28N4O4: 389.2111 [M+H]+
; found: 389.2134.
(S)-N-[1-(2-Butyl-2-cyano-1-methylhydrazinyl)-1-oxo-3-phenylpropan-2-
yl]-2,3-dihydrobenzo[b]ACHTUNGTRENNUNG[1,4]dioxine-6-carboxamide (1e): Prepared ac-
cording to the general procedure using 12e (155 mg, 0.38 mmol), sodium
acetate (123 mg, 1.5 mmol), and cyanogen bromide (160 mg, 1.5 mmol) in
anhydrous methanol (10 mL) to afford 1e (113 mg, 69%) as a white
1
solid. H NMR (500 MHz, CDCl3): d=0.99 (t, J=10.0 Hz, 3H), 1.47–1.56
(m, 2H), 1.74–1.83 (m, 2H), 2.96–3.21 (m, 2H), 3.26ACTHUNRTGNEUNG(s, 3H), 3.42- 3.54
(m, 2H), 4.25 (d, J=10.0 Hz, 4H), 5.39–5.43 (m, 1H), 6.79–6.87 (m, 2H),
7.18–7.33 ppm (m, 6H); 13C NMR (126 MHz, CDCl3): d=13.7, 19.6, 19.8,
28.6, 31.5, 37.7, 50.9, 53.8, 64.1, 64.5, 112.5, 116.6, 117.2, 120.6, 126.9,
127.2, 128.7, 129.2, 129.5, 135.8, 143.3, 146.7, 166.6, 173.5 ppm; LC-IT-
TOF/MS: m/z calcd for C24H28N4O4: 437.2111 [M+H]+; found: 437.2102.
(S)-N-[1-(2-Cyano-1,2-dimethylhydrazinyl)-4-methyl-1-oxopentan-2-yl]-
2,3-dihydrobenzo[b]ACTHNUTRGNEU[GN 1,4]dioxine-6-carboxamide (1k): Prepared according
to the general procedure using 12k (118 mg, 0.35 mmol), sodium acetate
(115 mg, 1.4 mmol), and cyanogen bromide (149 mg, 1.4 mmol) in anhy-
drous methanol (10 mL) to afford 1k (97 mg, 77%) as a white solid.
1H NMR (500 MHz, CDCl3): d=1.00 (d, J=5.0 Hz, 3H), 1.05 (d, J=
5.0 Hz, 3H), 1.56–1.81 (m, 3H), 3.23 (s, 3H), 3.34 (s, 3H), 4.26–4.30 (m,
4H), 5.23–5.28 (m, 1H), 6.58 (d, J=10.0 Hz, 1H), 6.88 (d, J=10.0 Hz,
1H), 7.27–7.32 ppm (m, 2H); 13C NMR (126 MHz, CDCl3): d=21.5, 32.3,
25.1, 29.7, 30.5, 41.0, 41.3, 48.2, 64.2, 64.5, 113.6, 116.6, 117.3, 120.6, 126.8,
143.4, 146.8, 167.0, 174.7 ppm; LC-IT-TOF/MS: m/z calcd for
C18H24N4O4: 361.1798 [M+H]+; found: 361.1808.
(S)-N-[1-(2-Cyano-1,2-dimethylhydrazinyl)-3-methyl-1-oxobutan-2-yl]-
2,3-dihydrobenzo[b]ACHTUNGTRENNUNG[1,4]dioxine-6-carboxamide (1 f): Prepared according
to the general procedure using 12 f (106 mg, 0.33 mmol), sodium acetate
(107 mg, 1.3 mmol), and cyanogen bromide (138 mg, 1.3 mmol) in anhy-
drous methanol (10 mL) to afford 1 f (80 mg, 70%) as a white solid.
1H NMR (500 MHz, CDCl3): d=1.04 (d, J=10.0 Hz, 3H), 1.07 (d, J=
10.0 Hz, 3H), 2.09–2.17 (m, 1H), 3.24 (s, 3H), 3.32 (s, 3H), 4.26–4.30 (m,
4H), 5.10–5.13 (m, 1H), 6.57 (d, J=10.0 Hz, 1H), 6.88 (d, J=5.0 Hz,
1H), 7.29–7.35 ppm (m, 2H); 13C NMR (126 MHz, CDCl3): d=18.1, 19.6,
30.2, 31.4, 41.2, 54.0, 64.2, 64.5, 113.9, 116.6, 117.3, 120.6, 127.0, 143.4,
146.8, 166.9, 173.0 ppm; LC-IT-TOF/MS: m/z calcd for C17H22N4O4:
347.1641 [M+H]+; found: 347.347.1648.
(S)-N-[1-(2-Benzyl-2-cyano-1-methylhydrazinyl)-4-methyl-1-oxopentan-2-
yl]-2,3-dihydrobenzo[b]ACTHNUTRGNEUG[N 1,4]dioxine-6-carboxamide (1l): Prepared ac-
cording to the general procedure using 12l (132 mg, 0.32 mmol), sodium
acetate (106 mg, 1.3 mmol), and cyanogen bromide (138 mg, 1.3 mmol) in
anhydrous methanol (10 mL) to afford 1l (131 mg, 81%) as a white solid.
1H NMR (500 MHz, CDCl3): d=0.96 (t, J=5.0 Hz, 6H), 1.50–1.81 (m,
3H), 3.14 (s, 3H), 4.28 (dd, J=5.0, 15.0 Hz, 4H), 4.63 (s, 2H), 5.41–5.45
(m, 1H), 6.67 (d, J=10.0 Hz, 1H), 6.89 (d, J=10.0 Hz, 1H), 7.31–
7.57 ppm (m, 7H); 13C NMR (126 MHz, CDCl3): d=21.4, 23.3, 25.0, 32.3,
41.3, 48.4, 58.9, 64.2, 64.6, 112.4, 116.7, 117.3, 120.7, 127.0, 127.4, 128.8,
129.3, 129.8, 130.4, 131.5, 143.4, 146.8, 167.1, 175.1 ppm; LC-IT-TOF/MS:
m/z calcd for C24H28N4O4: 437.2111 [M+H]+; found: 437.2124.
(S)-N-[1-(2-Benzyl-2-cyano-1-methylhydrazinyl)-3-methyl-1-oxobutan-2-
yl]-2,3-dihydrobenzo[b]ACHTUNGTRENNUNG[1,4]dioxine-6-carboxamide (1g): Prepared ac-
cording to the general procedure using 12g (140 mg, 0.35 mmol), sodium
acetate (115 mg, 1.4 mmol), and cyanogen bromide (149 mg, 1.4 mmol) in
anhydrous methanol (10 mL) to afford 1g (115 mg, 78%) as a white
solid. 1H NMR (500 MHz, CDCl3): d=1.03 (d, J=10.0 Hz, 3H), 1.05 (d,
J=10.0 Hz, 3H), 2.10–2.17 (m, 1H), 3.13 (s, 3H), 4.29 (dd, J=5.0,
10.0 Hz, 4H), 4.62 (dd, J=15.0, 20.0 Hz, 2H), 5.26–5.30 (m, 1H), 6.54 (d,
J=10.0 Hz, 1H), 6.91 (d, J=5.0 Hz, 1H), 7.30–7.44 (m, 6H), 7.55 ppm
(d, J=10.0 Hz, 1H); 13C NMR (126 MHz, CDCl3): d=18.0, 19.7, 31.5,
32.2, 54.2, 59.0, 64.2, 64.6, 112.7, 116.7, 117.3, 120.6, 127.2, 129.3, 129.7,
130.3, 131.6, 143.4, 146.8, 167.0, 174.1 ppm; LC-IT-TOF/MS: m/z calcd
for C23H26N4O4: 423.1594 [M+H]+; found: 423.1606.
(S)-N-[1-(2-Cyano-1-methyl-2-phenethylhydrazinyl)-4-methyl-1-oxopen-
tan-2-yl]-2,3-dihydrobenzo[b]ACTHUNRTGNEUNG[1,4]dioxine-6-carboxamide (1 m): Prepared
according to the general procedure using 12m (132 mg, 0.31 mg), sodium
acetate (98 mg, 1.2 mmol), and cyanogen bromide (127 mg, 1.2 mmol) in
anhydrous methanol (10 mL) to afford 1m (110 mg, 79%) as a white
solid. 1H NMR (500 MHz, CDCl3): d=0.91 (d, J=5.0 Hz, 3H), 0.93 (d,
J=5.0 Hz, 3H), 1.48–1.69 (m, 3H), 3.11–3.14 (m, 2H), 3.16 (s, 3H), 3.69–
3.74 (m, 1H), 3.81–3.87 (m, 1H), 4.25–4.29 (m, 4H), 5.11–5.15 (m, 1H),
(S)-N-[1-(2-Cyano-1-methyl-2-phenethylhydrazinyl)-3-methyl-1-oxobu-
tan-2-yl]-2,3-dihydrobenzo[b]
ACHTUNGTRENUN[NG 1,4]dioxine-6-carboxamide (1 h): Prepared
according to the general procedure using 12 h (136 mg, 0.33 mmol),
&
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Chem. Eur. J. 0000, 00, 0 – 0
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