Vol. 63, No. 3 (2015)
Chem. Pharm. Bull.
207
2
5
1
oil. [α] −16.46 (c=1.30, CH OH). H-NMR (CD OD) δ: Anal. Calcd for C H F N O S·3/2 H O: C, 51.23; H, 5.08; N,
D
3
3
33 36
6
4
7
2
1
.28–1.43 (11H, m, t-Bu and CH ), 1.47–1.54 (2H, m, CH ), 7.24. Found: C, 51.06; H, 5.28; N, 7.37.
2
2
1
.71–1.78 (2H, m, CH ), 1.86–1.94 (2H, m, CH ), 3.89 (3H, s,
1-[4-[4-[[[(1S,2S)-2-Amino-1,2-diphenylethyl]amino]sul-
2
2
N-Me), 3.92 (2H, t, J=6.4Hz, CH O), 4.20 (2H, t, J=7.3Hz, fonyl]phenoxy]butyl]-pyridinium Mono(trifluoroacetate)
2
CH N), 4.53 (1H, d, J=8.2Hz, CH(Ph)NH), 4.79 (1H, d, Salt with Trifluoroacetic Acid (3c) Compound 3c was
2
J=8.2Hz, CH(Ph)NH), 6.67 (2H, d, J=9.0Hz, SO Ar-H), synthesized from 7c (125mg, 0.196mmol) in the same manner
2
6
.87–7.12 (10H, m, 2×Ph-H), 7.37 (2H, d, J=8.8Hz, SO Ar- as the synthesis of 3a. Yield: 140mg (96%). Yellow amor-
2
25 1
H), 7.53 (1H, d, J=1.8Hz, imidazole-H), 7.61 (1H, d, J=1.8Hz, phous. [α]D −22.14 (c=1.40, CH OH). H-NMR (CD OD) δ:
imidazole-H), 8.92 (1H, s, 2-imidazole-H). C-NMR (CD OD) 1.79–1.86 (2H, m, CH ), 2.13–2.21 (2H, m, CH ), 3.96 (2H, t,
3
3
13
3
2
2
δ: 26.5, 26.9, 28.7, 29.8, 31.0, 36.5, 50.7, 61.1, 64.1, 69.1, 80.6, J=6.1Hz, CH O), 4.53 (1H, d, J=11.0Hz, CH(Ph)NH), 4.67
2
1
15.3, 123.60, 123.64, 124.9, 125.0, 128.1, 128.2, 128.4, 128.6, (1H, d, J=11.4Hz, CH(Ph)NH), 4.71 (2H, t, J=7.8Hz, CH N),
2
1
29.0, 129.1, 129.9, 133.9, 137.8, 139.8, 141.0, 157.8, 163.2. IR 6.69 (2H, d, J=9.0Hz, SO Ar-H), 6.75–7.29 (10H, m, 2×Ph-
2
−1
(
1
KBr) cm : 3374, 3207, 3037, 2913, 1694, 1592, 1492, 1318, H), 7.47 (2H, d, J=9.0Hz, SO Ar-H), 8.10 (2H, t, J=7.1Hz,
2
250, 1149, 1088, 716, 580, 554. HR-MS (FAB+) m/z: Found, 3,5-pyridine-H), 8.57 (1H, t, J=7.8Hz, 4-pyridine-H), 9.03
+
+
13
633.3108 (M) (Calcd for C H N O S : 633.3111).
(2H, d, J=5.5Hz, 2,6-pyridine-H). C-NMR (CD OD) δ: 26.6,
35
45
4
5
3
1
-[4-[4-[[[(1S,2S)-2-Amino-1,2-diphenylethyl]amino]- 29.2, 60.6, 62.7, 63.0, 68.5, 115.4, 128.7, 128.8, 129.15, 129.21,
sulfonyl]phenoxy]butyl]-3-methyl-1H-imidazolium 129.3, 129.5, 129.9, 130.18, 130.24, 130.3, 133.3, 134.9, 136.7,
1
9
Mono(trifluoroacetate) Salt with Trifluoroacetic Acid 145.9, 146.9, 163.2. F-NMR (CD OD) δ: 1.85 (s). IR (KBr)
(
3
−1
3a) TFA (0.306mL, 4.12mmol) was added to 7a (264mg, cm : 3379, 3042, 2913, 2671, 1680, 1629, 1606, 1198, 1175,
0
.412mmol) at 0°C under N , and the mixture was stirred for 1149, 1126, 1092, 698. HR-MS (FAB+) m/z: Found, 502.2159
2
+
+
3.5h. The volatile material was removed under reduced pres- (M) (Calcd for C H N O S : 502.2164). HR-MS (CI-,
29 32 3 3
−
−
sure. Toluene (5mL) was added to the residue, and the volatile isobutane) m/z: Found, 112.9842 (X) (Calcd for C F O :
material was removed (×3) to obtain compound 3a. Yield: 112.9850). MS (CI) m/z (rel. int. %): 113 (X , 100). Anal. Calcd
2
3
2
−
2
5
2
99mg (99%). Yellow oil. [α]D −41.60 (c=0.50, CH OH). for C H F N O S·1/2H O: C, 53.66; H, 4.64; N, 5.69. Found:
3 33 33 6 3 7 2
1
H-NMR (CD OD) δ: 1.73–1.80 (2H, m, CH ), 1.98–2.07 C, 53.67; H, 4.75; N, 5.77.
3
2
(
2H, m, CH ), 3.90 (3H, s, N-Me), 3.95 (2H, t, J=6.0Hz,
1-[4-[4-[[[(1S,2S)-2-Amino-1,2-diphenylethyl]amino]-
2
CH O), 4.27 (2H, t, J=7.3Hz, CH N), 4.53 (1H, d, J=10.8Hz, sulfonyl]phenoxy]butyl]-3-methylbenzimidazolium
2
2
CH(Ph)NH), 4.66 (1H, d, J=10.8Hz, CH(Ph)NH), 6.69 (2H, d, Mono(trifluoroacetate) Salt with Trifluoroacetic Acid (3d)
J=8.8Hz, SO Ar-H), 6.75–7.22 (10H, m, 2×Ph-H), 7.47 (2H, d, Compound 3d was synthesized from 7d (94mg, 0.136mmol)
2
J=9.0Hz, SO Ar-H), 7.54 (1H, d, J=1.8Hz, imidazole-H), 7.63 in the same manner as the synthesis of 3a. Yield: 108mg
2
2
5
1
(
1H, d, J=1.8Hz, imidazole-H), 8.97 (1H, s, 2-imidazole-H). (99%). Yellow oil. [α]D −35.93 (c=1.92, CH OH). H-NMR
C-NMR (CD OD) δ: 26.7, 27.9, 36.5, 50.4, 60.7, 63.0, 68.6, (CD OD) δ: 1.84–1.89 (2H, m, CH ), 2.12–2.19 (2H, m, CH ),
3
1
3
3
3
2
2
1
15.4, 123.6, 125.0, 128.7, 128.8, 129.1, 129.2, 129.9, 130.2, 3.97 (3H, t, J=6.0Hz, CH O), 4.12 (3H, s, N-Me), 4.51 (1H,
2
19
130.3, 133.2, 134.8, 136.7, 137.9, 163.3. F-NMR (CD OD) d, J=11.0Hz, CH(Ph)NH), 4.58 (2H, t, J=7.3Hz, CH N), 4.65
3
2
−1
δ: 1.80 (s). IR (KBr) cm : 3364, 3046, 2910, 1671, 1197, (1H, d, J=11.0Hz, CH(Ph)NH), 6.66 (2H, d, J=8.8Hz, SO Ar-
2
+
1
153. HR-MS (FAB+) m/z: Found, 505.2277 (M) (Calcd for H), 6.73–7.22 (10H, m, 2×Ph-H), 7.44 (2H, d, J=9.0Hz,
+
C H N O S : 505.2273). HR-MS (CI-, isobutane) m/z: Found, SO Ar-H), 7.69–7.72 (2H, m, benzimidazole-H), 7.90–7.98
2
8
33
4
3
2
−
−
112.9855 (X) (Calcd for C F O : 112.9850). MS (CI) m/z (rel. (2H, m, benzimidazole-H), 9.53 (1H, s, 2-benzimidazole-H).
2 3 2
−
13
int. %): 113 (X , 100). Anal. Calcd for C H F N O S·5/2H O:
C-NMR (CD OD) δ: 26.9, 27.0, 33.8, 48.1, 60.7, 63.0, 68.5,
3
32
34
6
4
7
2
C, 49.42; H, 5.05; N, 7.20. Found: C, 49.45; H, 4.82; N, 6.85.
114.30, 114.34, 115.3, 128.18, 128.20, 128.7, 128.8, 129.15,
1
-[4-[4-[[[(1S,2S)-2-Amino-1,2-diphenylethyl]amino]- 129.22, 129.9, 130.2, 130.3, 132.7, 133.2, 133.6, 134.9, 136.7,
19
−1
sulfonyl]phenoxy]butyl]-2,3-dimethyl-1H-imidazolium 143.4, 163.2. F-NMR (CD OD) δ: 1.34 (s). IR (KBr) cm :
3
Mono(trifluoroacetate) Salt with Trifluoroacetic Acid (3b) 3372, 3127, 3080, 2940, 2861, 1690, 1670, 1595, 1570, 1497,
Compound 3b was synthesized from 7b (60mg, 0.091mmol) 1255, 1198, 1175, 1149, 700. HR-MS (FAB+) m/z: Found,
in the same manner as the synthesis of 3a. Yield: 64mg (95%). 555.2433 (M)+ (Calcd for C H N O S : 555.2430). HR-MS
+
32
35
4
3
2
4
1
−
−
Yellow oil. [α] −34.26 (c=1.36, CH OH). H-NMR (CD OD) (CI-, isobutane) m/z: Found, 112.9842 (X) (Calcd for C F O :
D
3
3
2
3
2
−
δ: 1.77–1.83 (2H, m, CH ), 1.92–1.98 (2H, m, CH ), 2.61 (3H, 112.9850). MS (CI) m/z (rel. int. %): 113 (X , 100). Anal. Calcd
2
2
s, 2-imidazole-Me), 3.79 (3H, s, N-Me), 3.96 (2H, t, J=6.0Hz, for C H F N O S·4/3H O: C, 53.59; H, 4.83; N, 6.94. Found:
36
36
6
4
7
2
CH O), 4.20 (2H, t, J=7.4Hz, CH N), 4.51 (1H, d, J=11.0Hz, C, 53.78; H, 4.92; N, 6.73.
2
2
CH(Ph)NH), 4.65 (1H, d, J=10.8Hz, CH(Ph)NH), 6.70 (2H, d,
1-[4 -[4 -[[[(1S, 2S )-2-Amino-1, 2-diphenylethyl]-
J=9.0Hz, SO Ar-H), 6.73–7.41 (10H, m, 2×Ph-H), 7.45 (1H, amino]sulfonyl]phenoxy]butyl]-1-methylpyrrolidinium
2
d, J=1.8Hz, imidazole-H), 7.47 (2H, d, J=8.8Hz, SO Ar-H), Mono(trifluoroacetate) Salt with Trifluoroacetic Acid (3e)
2
13
7
9
1
1
.51 (1H, d, J=1.8Hz, imidazole-H). C-NMR (CD OD) δ: Compound 3e was synthesized from 7e (60mg, 0.093mmol)
3
.5, 26.8, 27.5, 35.4, 49.1, 60.7, 63.0, 68.7, 115.4, 122.1, 123.7, in the same manner as the synthesis of 3a. Yield: 61mg
2
5
28.8, 128.9, 129.18, 129.24, 130.0, 130.29, 130.34, 133.3, (92%). Yellow amorphous. [α] −50.40 (c=1.00, CH OH).
D 3
19 1
34.9, 136.7, 145.8, 163.3. F-NMR (CD OD) δ: 1.50 (s). IR
H-NMR (CD OD) δ: 1.78–1.85 (2H, m, CH ), 1.91–1.99
3 2
3
−1
(
KBr) cm : 3350, 3317, 3060, 2910, 2870, 1769, 1731, 1680, (2H, m, CH ), 2.21 (4H, brs, 3,4-pyrrolidine-H), 3.06 (3H, s,
2
1
672, 1592, 1494, 1255, 1198, 1167, 600. HR-MS (FAB+) m/z: N-Me), 3.41 (2H, brt, J=8.4Hz, CH N), 3.47–3.58 (4H, m,
2
+
+
Found, 519.2437 (M) (Calcd for C H N O S : 519.2430). 2,5- pyrrolidine-H), 3.99 (2H, t, J=6.0Hz, CH O), 4.52 (1H, d,
HR-MS (CI-, isobutane) m/z: Found, 112.9853 (X) (Calcd for J=10.8Hz, CH(Ph)NH), 4.65 (1H, d, J=10.8Hz, CH(Ph)NH),
C F O : 112.9850). MS (CI) m/z (rel. int. %): 113 (X , 100). 6.73 (2H, d, J=9.0Hz, SO Ar-H), 6.75–7.22 (10H, m, 2×Ph-
2
9
35
4
3
2
−
−
−
2
3
2
2