RCHH HARM
A P
Arch. Pharm. Chem. Life Sci. 2016, 349, 211–223
M. Bednarski et al.
Archiv der Pharmazie
Spectral and physical data confirmed the structures of the
obtained compounds.
(S)-3c: Yield 51%, mp 111–112°C (methylene chloride),
½aꢄD ¼ ꢁ2.95° (0.98, acetone).
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(2RS)-1-(1H-Indol-4-yloxy)-3-(2-(2-methylophenoxy)-
ethylamino)propan-2-ol, (RS)-3a
(2RS)-1-(2-(3,4-Dimethoxyphenoxy)ethylamino)-3-(1H-
indol-4-yloxy)propan-2-ol, (RS)-3d
Yield 56% as colorless crystals from acetone, mp 93–95°C. IR
(KBr): 3430, 3393, 2945, 1586, 1501, 1363, 1245, 1124, 1056, 740.
1H NMR (CDCl3): 8.22 (brs, 1H), 7.15–7.06 (m, 4H), 7.02 (d, J 8.10,
1H),6.86(t,J7.35, 1H), 6.82(d, J8.10,1H),6.63(t, J2.22,1H),6.53
(d, J7.60,1H),4.18–4.14(m, 3H),4.08(t, J5.10,2H),3.09(t, J5.10,
2H), 3.02–3.0 (m, 1H), 2.95–2.92(m, 1H), 2.60–2.40(brs, 2H), 2.21
(s, 3H). 13C NMR (CDCl3): 156.8, 152.3, 137.3, 130.7, 126.84,
126.79, 122.74, 122.70, 120.6, 118.7, 111.1, 104.8, 100.9, 99.9,
70.6, 68.5, 67.4, 51.8, 48.9, 16.3. UV (CHCl3), (nm), lmax: 267 (lge
3.95); 290 (lge 3.82) (c 0.416 mg/10 mL). EA [%] for C20H24N2O3,
calculated:C70.57,H 7.11, N 8.23;found:C70.63,H 7.30,N 8.40.
(R)-3a: Yield 68%, mp 101–103°C (methylene chloride/
Yield 62% as colorless crystals from methylene chloride, mp
131–132°C. IR (KBr): 3387, 3304, 2920, 1596, 1513, 1449, 1235,
1119, 1020, 749. 1H NMR (CD3OD): 7.08 (d, J 3.0, 1H), 7.02–6.97
(m, 2H), 6.82 (d, J 8.75, 1H), 6.55 (d, J 2.70, 1H), 6.53 (d, J 3.0, 1H),
6.49(dd, J 8.75and2.70, 1H), 6.45(dd, J 8.75and2.70, 1H), 4.25–
4.17 (m, 1H), 4.15–4.12 (m, 1H), 4.07–4.04 (m, 3H), 3.76 and 3.74
(2s, 6H), 3.03–2.98 (m, 3H), 2.89–2.84 (dd, J 12.20 and 7.97, 1H).
13CNMR(CD3OD):154.9, 153.6, 151.5, 144.9, 138.8, 123.9, 123.0,
120.0, 114.2, 105.7, 105.3, 102.2, 101.0, 100.0, 71.8, 69.8, 69.2,
57.0, 56.1, 53.5, 49.9. UV (EtOH), (nm), lmax: 220 (lge 4.73),
(c 0.084 mg/10mL). MS HR (ESI): for C21H27N2O5 ([MþH]þ)
calculated: 387.1915; found: 318.1906. EA [%] for C21H26N2O5,
calculated: C 65.27, H 6.78, N 7.25; found: C 65.15, H 6.67,
N 7.20.
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hexane), ½aꢄD ¼ þ2.4° (1.0, CHCl3).
(S)-3a: Yield 46%, mp 101–103°C (methylene chloride/
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hexane), ½aꢄD ¼ ꢁ2.5° (1.0, CHCl3).
(R)-3d: Yield 30%, as oil.
(S)-3d: Yield 44%, as oil.
(2RS)-1-(2-(2,3-Dimethoxyphenoxy)ethylamino)-3-(1H-
indol-4-yloxy)propan-2-ol, (RS)-3b
(2RS)-1-(2-(3,5-Dimethoxyphenoxy)ethylamino)-3-(1H-
indol-4-yloxy)propan-2-ol, (RS)-3e
Yield 43% as colorless crystals from methanol/methylene
chloride, mp 109–111°C. IR (KBr): 3318, 2935, 1616, 1600, 1588,
1496, 1479, 1248, 1107, 997. 1H NMR (CD3OD): 7.12 (d, J 3.12,
1H), 7.04–7.01 (m, 3H), 6.70 (d, J 8.40, 2H), 6.58 (d, J 3.12, 1H),
6.54 (dd, J 6.15 and 2.25, 1H), 4.23–4.17 (m, 1H), 4.16–4.13
(m, 4H), 3.86 (s, 3H), 3.78 (s, 3H), 3.09 (t, J 5.30, 2H), 3.05 (dd, J
12.12 and 3.85, 1H), 2.91 (dd, J 12.12 and 8.15, 1H). 13C NMR
(CD3OD): 155.9, 154.9, 154.6, 140.8, 140.2, 126.2, 124.9, 123.9,
121.2, 109.4, 108.1, 107.0, 102.2, 100.7, 72.8, 71.0, 70.5, 62.3,
57.5, 54.4, 50.4. EA [%] for C21H26N2O5, calculated: C 65.27, H
6.78, N 7.25; found: C 64.88, H 6.61, N 7.28.
Yield 86% as colorless crystals from methylene chloride/
hexane, mp 121–123°C. IR (KBr): 3421, 3405, 3294, 3124, 2933,
1614, 1595, 1467, 1194, 1170, 741. 1H NMR (CD3OD): 7.08 (d, J
3.12, 1H), 7.02–6.98 (m, 2H), 6.54 (d, J 3.12, 1H), 6.50 (dd, J 6.22
and 2.22, 1H), 6.10 (d, J 2.10, 2H), 6.09–6.08 (m, 1H), 4.22–4.17
(m, 1H), 4.16–4.05 (m, 4H), 3.71 (s, 6H), 3.03 (t, J 5.45, 2H), 3.00
(dd, J 12.40 and 4.20, 1H), 2.86 (dd, J 12.40 and 8.02, 1H). 13
C
NMR (CD3OD): 163.2 (2C), 162.2, 153.7, 139.4, 124.1, 123.1,
120.3, 106.2, 101.3, 99.8, 94.6 (2C), 94.4, 72.1, 70.1, 68.2, 55.9
(3C), 53.8. EA [%] for C21H26N2O5, calculated: C 65.27, H 6.78,
N 7.25; found: C 65.37, H 6.69, N 7.30.
(R)-3b: Yield 65%, mp 135–136°C (methylene chloride),
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½aꢄD ¼ þ3.4° (0.99, MeOH).
(R)-3e: Yield, 70%, mp 107–108°C (methylene chloride/
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(S)-3b: Yield 46%, mp 135–136°C (methylene chloride),
hexane), ½aꢄD ¼ þ6.7° (1.0, MeOH).
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½aꢄD ¼ ꢁ3.2° (0.99, MeOH).
(S)-3e: Yield 70%, mp 105–106°C (methylene chloride/
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hexane), ½aꢄD ¼ ꢁ6.6° (1.0, MeOH).
(2RS)-1-(2-(2,6-Dimethoxyphenoxy)ethylamino)-3-(1H-
indol-4-yloxy)propan-2-ol, (RS)-3c
(R)-1-((2-(2,6-Dimethoxyphenoxy)ethyl)-((S)-2-hydroxy-3-
(1H-indol-4-yloxy)propyl))amino)-3-(1H-indol-4-yloxy)-
propan-2-ol, by-product 4
Yield 35% as colorless crystals from acetone, mp 113–114°C. IR
(KBr): 3299, 3290, 3253, 2942, 2925, 2874, 2838, 1606, 1479,
1256, 1110, 1046, 749, 721. 1H NMR (CDCl3): 8.26 (brs, 1H),
7.10–7.08(m, 1H),7.06(d, J7.70,1H), 7.00(d,J 8.15, 1H), 6.52(t, J
8.40, 1H), 6.65 (t, J 2.25, 1H), 6.56 (d, J 8.40, 2H), 6.54 (d, J 7.70,
1H), 4.20–4.11 (m, 5H), 3.82 (s, 6H), 3.01–2.98 (m, 1H), 2.94 (t, J
4.95,2H)2.90–2.87(m,1H), 2.20–1.80(brs,2H). 13CNMR(CDCl3):
153.6 (2C), 152.5, 137.3, 136.8, 123.7, 122.7, 122.6, 118.8, 105.2
(2C), 104.7, 100.8, 99.9, 72.6, 70.5, 68.5, 56.0 (2C), 51.7, 49.6. UV
(EtOH), (nm), lmax: 220 (lge 4.76), (c 0.064mg/10 mL). MS HR
(ESI): for C21H27N2O5 ([MþH]þ) calculated: 387.1915; found:
318.1920. EA [%] for C21H26N2O5, calculated: C 65.27, H 6.78, N
7.25; found: C 65.26, H 6.69, N 7.19.
As colorless crystals from methylene chloride, mp 75–76°C. IR
(KBr): 3405, 3106 (OH and NH), 2938, 2837 (C–H), 1597, 1588,
1510, 1478, 1363, 1245, 1109, 745. 1H NMR (acetone-d6): 10.17
(brs,2H,NH),7.17(t, J2.70, 2H), 7.03–6.96(m, 5H), 6.65(d, J8.40,
2H), 6.57–6.56 (m, 2H), 6.52 (dd, J 7.38 and0.63, 2H), 5.62 (s, 2H),
4.27–4.12 (m, 8H), 3.80 (s, 6H, 2 ꢅ OCH3), 3.06–2.97 and
2.92–2.83 (2m, 8H). 13C NMR (aceton-d6): 154.5 (2C), 153.6
(2C), 138.7 (2C), 138.2, 124.4, 123.7, 123.5, 122.9 (2C), 119.0 (2C),
106.3 (2C), 105.5 (2C), 100.9 (2C), 99.9 (2C), 72.2 (2C), 71.3 (2C),
68.4 (2C), 59.9 (2C), 56.4 (2 ꢂ OCH3), 54.9. EA [%] for C32H37N3O7
ꢂ CH2Cl2, calculated: C 60.00, H 5.95, N 6.36; found: C 59.34,
H 5.78, N 6.27. UV (EtOH), (nm), lmax: 220 (lge ¼ 4.98),
(R)-3c: Yield 45%, mp 111–112°C (methylene chloride),
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½aꢄD ¼ þ2.18° (0.98, acetone).
(c ¼ 0.058 mg/10 mL). ½aꢄD ¼ þ39.0° (1.005, CHCl3).
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