A. M. Waszkielewicz et al. / Bioorg. Med. Chem. 24 (2016) 1793–1810
1805
ppm): 7.01 (dd, J = 7.9, J = 7.5, 1H, H-5); 6.77 (d, J = 7.9, 1H, H-4);
6.74 (d, J = 7.5, 1H, H-6); 4.54 (t, J = 5.2, 1H, OH); 4.03–3.97 (m,
1H, CHH–OAr); 3.97–3.91 (m, 1H, CHH–OAr); 3.27–3.24 (m, 1H,
CHH–OH); 3.24–3.17 (m, 1H, CHH–OH); 2.97–2.90 (m, 1H, CHH–
N); 2.90–2.83 (m, 1H, CHH–N); 2.71–2.62 (m, 1H, CH); 2.20 (s,
3H, CH3–Ar (2)); 2.07 (s, 3H, CH3–Ar (3)); 1.89 (br s, 1H, NH);
0.92 (d, J = 6.4, 3H, CH3).
122.01 (C-4), 109.29 (C-6), 71.61 (CH), 67.93 (Ar–O–CH2–), 57.54
(N–CH2–), 48.17 (–CH2–N), 19.69 (CH3–Ar (3)), 11.37 (CH3–Ar (2)).
4.1.1.7. R,S-2N-[(2,3-Dimethylphenoxy)propyl]aminopropan-1-
ol (7). White solid. Yield = 64%; M = 237.34; C14H23NO2; mp 88–
90 °C; [%calcd
/
]
C70.85
/
,
H9.77
/
,
N5.90
/ ;
5.86
Rf = 0.24
analyzed
70.89
10.02
(CH3OH); IR (KBr, cmꢀ1
) v: 3260, 3110, 2957, 2924, 2824, 2599,
2359, 1593, 1481, 1257, 1091, 768; 1H NMR (d ppm): 7.00 (dd,
J = 8.2, J = 7.5, 1H, H-5); 6.76 (d, J = 8.5, 1H, H-4); 6.73 (d, J = 7.5,
1H, H-6); 4.45 (br s, 1H, OH); 3.91 (t, J = 6.2, 2H, CH2–OAr);
3.28–3.18 (m, 2H, CH2–OH); 2.80–2.70 (m, 2H, CH2–N); 2.69–
2.55 (m, 1H, CH); 2.20 (s, 3H, CH3–Ar (2)); 2.07 (s, 3H, CH3–Ar
(3)); 1.87–1.80 (m, 2H, R–CH2–R); 1.56 (br s, 1H, NH); 0.90
(d, J = 6.4, 3H, CH3).
4.1.1.2. 2N-[(2,3-Dimethylphenoxy)ethyl]amino-2-methylpropan-
1-ol (2). White solid. Yield = 62%; M = 237.34; C14H23NO2; mp 75–
77 °C; [%calcd
/
analyzed] C70.85
/
70.70, H9.77
/
9.90, N5.90
/
5.72; Rf = 0.44 (CH3OH);
IR (KBr, cmꢀ1
)
v: 3295, 3154, 2986, 2971, 2926, 2877, 2827, 2756,
1
2557, 2359, 1584, 1464, 1263, 1068, 768; H NMR (d ppm): 7.05 (dd,
J = 8.0, J = 7.5, 1H, H-5); 6.80 (d, J = 8.0, 1H, H-6); 6.78 (d, J = 7.5, 1H,
H-4); 4.68 (t, J = 3.1, 1H, OH); 3.98 (t, J = 5.7, 2H, CH2–OAr); 3.24 (d,
J = 3.1, 2H, CH2–OH); 2.86 (t, J = 5.7, 2H, CH2–N); 2.24 (s, 3H, CH3–Ar
(3)); 2.12 (s, 3H, CH3–Ar (2)); 1.82 (br s, 1H, NH); 1.01 (s, 6H, 2ꢃ CH3).
4.1.1.8. R,S-2N-[(2,3-Dimethylphenoxy)propyl]aminobutan-1-ol
(8). White solid. Yield = 60%; M = 251.37; C15H25NO2; mp 82–
84 °C; [%calcd
/
analyzed] C71.67
/
71.43, H10.02
/
10.01, N5.57
/
5.53; Rf = 0.24
4.1.1.3. R,S-2N-[(2,3-Dimethylphenoxy)ethyl]aminobutan-1-ol
(3). White solid. Yield = 55%; M = 237.34; C14H23NO2; mp 55–
(CH3OH); IR (KBr, cmꢀ1
) v: 3258, 3100, 2964, 2922, 2863, 2815,
1910, 1584, 1464, 1255, 1096, 768; 1H NMR (d ppm): 7.00 (dd,
J = 8.2; J = 7.6, 1H, H-5); 6.77 (d, J = 8.2, 1H, H-6); 6.70 (d, J = 7.6,
1H, H-4); 4.40 (br s, 1H, –OH); 3.99 (t, J = 6.2, 2H, Ar–O–CH2–);
3.39–3.21 (m, 2H, CH2–OH); 2.69 (t, J = 6.8, 2H, –CH2–N);
2.41–2.31 (m, 1H, CH); 2.20 (s, 3H, CH3–Ar (3)); 2.07 (s, 3H, CH3–
Ar (2)); 1.84 (tt, J = 6.8, J = 6.2, 2H, R–CH2–R); 1.48 (br s, 1H, –
NH); 1.39–1.28 (m, 2H, –CH2–CH3); 0.83 (t, J = 7.5, 3H, R–CH3);
13C NMR (d ppm): 156.40 (C-1), 137.02 (C-3), 125.77 (C-5),
124.03 (C-2), 121.75 (C-4), 109.07 (C-6), 65.96 (Ar–O–CH2–),
62.47 (CH2–OH), 60.22 (CH), 43.42 (–CH2–N), 29.93 (R–CH2–R),
23.60 (CH3–CH2–), 19.64 (CH3–Ar(3)), 11.29 (CH3–Ar(2)), 9.94
(CH3–CH2–).
56 °C; [%calcd
/
analyzed] C70.86
/
70.76, H9.77
/
9.76, N5.90
/
5.82; Rf = 0.51 (CH3-
OH); IR (KBr, cmꢀ1
)
v: 3295, 3158, 2964, 2931, 2875, 2837, 1900,
1585, 1470, 1263, 1109, 1062, 762; 1H NMR (d ppm): 7.01 (dd,
J = 8.3, J = 7.7, 1H, H-5); 6.77 (d, J = 8.3, 1H, H-6); 6.74 (d, J = 7.7,
1H, H-4); 4.46 (t, J = 4.4, 1H, OH); 3.98 (dt, J = 9.5, J = 5.5, 1H,
CHH–OAr); 3.94 (dt, J = 9.5, J = 5.5, 1H, CHH–OAr); 3.43–3.20 (m,
2H, CH2–OH); 2.90 (t, J = 5.5, 2H, CH2–N); 2.49–2.41 (m, 1H, CH);
2.20 (s, 3H, CH3–Ar (2)); 2.07 (s, 3H, CH3–Ar (3)); 1.81 (br s, 1H,
NH); 1.41–1.31 (m, 2H, CH2–CH3); 0.85 (t, J = 7.3, 3H, CH2–CH3).
4.1.1.4.
hexan-1-ol (4). White solid. Yield = 57%; M = 263.38; C16H25NO2;
mp 95–97 °C; [%calcd analyzed] C72.97 H9.57 N5.32
Rf = 0.54 (CH3OH/ethyl acetate 1:1); IR (KBr, cmꢀ1
D,L-trans-2N-[(2,3-Dimethylphenoxy)ethyl]aminocyclo-
/
/
,
/
,
/ ;
5.23
4.1.1.9. N-[(2,3-Dimethylphenoxy)propyl]piperidin-3-ol (9). White
72.71
9.26
)
v
: 3298, 3113,
solid. Yield = 53%; M = 263.38; C16H25NO2; mp 86–88 °C; [%calcd
/
]
analyzed
2929, 2858, 2816, 2365, 1585, 1461, 1264, 1111; 1H NMR (d
ppm): 6.97–7.09 (m, 1H, Ar–H5); 6.78 (d, J = 7.69, 1H, Ar–H4);
6.71 (d, J = 8.21, 1H, Ar–H6); 4.05 (t, J = 5.26, 2H, O–CH2–CH2–
NH); 3.33 (br s, 1H, NH); 3.27–3.10 (m, 2H, O–CH2–CH2–NH);
2.89 (dt, J = 12.50, J = 4.78, 1H, CH–OH); 2.27 (s, 3H, CH3–Ar (2));
2.34–2.22 (m, 1H, CH–NH); 2.15 (s, 3H, CH3–Ar (3)); 2.13–2.00
(m, 2H, cyclohex); 1.80–1.67 (m, 2H, cyclohex); 1.35–1.17 (m,
3H, cyclohex); 1.09–0.92 (m, 1H, cyclohex).
C72.97
/
72.48, H9.57
/
9.45, N5.32
/
5.25; Rf = 0.54 (CH3OH/ethyl acetate 1:1);
cLogP = 2.76; IR (KBr, cmꢀ1
)
v: 3149, 2947, 2867, 2826, 2775, 2513,
2149, 1914, 1584, 1467, 1068; 1H NMR (d ppm): 7.08–6.99 (m, 1H,
Ar–H5); 6.77 (d, J = 7.44, 1H, Ar–H4); 6.70 (d, J = 8.21, 1H, Ar–H6);
3.99 (t, J = 6.28, 2H, O–CH2–CH2–CH2–NH); 3.82 (br s, 1H, NH); 2.61–
2.45 (m, 5H, O–CH2–CH2–CH2–NH, CH–OH, pip-H); 2.42 (br s, 1H,
OH); 2.36–2.28 (m, 1H, pip-H); 2.27 (s, 3H, CH3–Ar (2)); 2.14 (s, 3H,
CH3–Ar (3)); 2.04–1.90 (m, 2H, O–CH2–CH2–CH2–NH); 1.88–1.72 (m,
1H, pip); 1.69–1.46 (m, 3H, pip).
4.1.1.5. N-[(2,3-Dimethylphenoxy)ethyl]piperidin-4-ol (5). White
solid. Yield = 53%; M = 249.35; C15H23NO2; mp 71–72 °C; [%calcd
/
]
4.1.1.10.
(10). White solid. Yield = 56%; M = 263.38; C16H25NO2; mp 68–
70 °C; [%calcd analyzed] C72.97 73.15, H9.57 9.42, N5.32
5.29; Rf = 0.39 (CH3-
OH/ethyl acetate 1:1); cLogP = 2.74; IR (KBr, cmꢀ1
: 3133, 2959,
1N-[(2,3-Dimethylphenoxy)propyl]piperidin-4-ol
analyzed
C72.25
/
72.44, H9.30
/ /5.59; Rf = 0.47 (CH3OH/ethyl acetate 1:1); IR
9.10, N5.62
(KBr, cmꢀ1
)
v
: 3153, 2974, 2943, 2912, 2866, 2798, 2688, 2599, 2503,
/
/
/
/
1
1581, 1459, 1254, 998; H NMR (d ppm): 7.04 (t, J = 7.9, 1H, Ar–H5);
6.78 (d, J = 7.8, 1H, Ar–H4); 6.70 (d, J = 8.2, 1H, Ar–H6); 4.08 (t, J = 5.9,
2H, Ar–O–CH2); 3.74–3.68 (m, 1H, CH–OH); 2.93–2.88 (m, 2H, pip);
2.84 (t, J = 5.6, 2H, CH2–N); 2.37–2.29 (m, 2H, pip); 2.27 (s, 3H, CH3–
Ar); 2.14 (s, 3H, CH3–Ar); 1.95–1.87 (m, 2H, pip); 1.68–1.54 (m, 2H, pip).
) v
2874, 2818, 2802, 2748, 2362, 2140, 1900, 1582, 1468, 1261; 1H
NMR (d ppm): 7.08–6.99 (m, 1H, Ar–H5); 6.76 (d, J = 7.44, 1H,
Ar–H4); 6.70 (d, J = 8.21, 1H, Ar–H6); 3.99 (t, J = 6.16, 2H, O–CH2–
CH2–CH2–NH); 3.71 (m, 1H, CH–OH); 2.91–2.73 (m, 2H, pip);
2.61–2.47 (m, 2H, O–CH2–CH2–CH2–NH); 2.26 (s, 3H, CH3–Ar
(2)); 2.22–2.15 (m, 2H, pip); 2.14 (s, 3H, CH3–Ar (3)); 2.07–1.84
(m, 4H, pip); 1.66–1.52 (m, 2H, O–CH2–CH2–CH2–NH); 1.47 (br s,
1H, OH).
4.1.1.6. R,S-2N-[(2,3-Dimethylphenoxy)ethyl]amino-1-pheny-
lethan-1-ol (6). White solid. Yield = 67%; M = 285.38; C18H23NO2;
mp 118–120 °C; [%calcd
/
analyzed] C75.75
/
75.83, H8.12
/
8.28, N4.91
/
;
4.82
Rf = 0.62 (CH3OH); cLogP = 3.03; IR (KBr, cmꢀ1
) v: 3310, 3064,
3033, 2975, 2921, 2899, 2871, 2836, 2735, 2519, 2364, 1892,
1588, 1453, 1266, 1108, 762; 1H NMR (d ppm): 7.39–7.18 (m,
5H, H-20-H60); 7.01 (dd, J = 8.2, J = 7.6, 1H, H-5); 6.76 (d, J = 8.2,
1H, H-6); 6.73 (d, J = 7.6, 1H, H-4); 5.30 (br s, 1H, –OH); 4.65 (t,
J = 6.3, 1H, CH); 3.97 (t, J = 5.5, 2H, Ar–O–CH2–); 2.92 (t, J = 5.5,
2H, –CH2–N); 2.73 (d, J = 6.3, 2H, N–CH2–); 2.20 (s, 3H, CH3–Ar
(3)); 2.03 (s, 3H, CH3–Ar (2)); 1.92 (br s, 1H, –NH); 13C NMR (d
ppm): 156.37 (C-1), 144.54 (C-10), 137.15 (C-3), 127.90 (C-30, C-
50), 126.75 (C-40), 125.89 (C-20, C-60), 125.85 (C-5), 124.19 (C-2),
4.1.1.11. R,S-2N-[(2,3-Dimethylphenoxy)propyl]amino-1-phe-
nylethan-1-ol (11). White solid. Yield = 62%; M = 299.42;
C
19H25NO2; mp 111–112 °C; [%calcd
/
analyzed] C76.22
/
76.21, H8.42
/
,
8.43
N4.68 4.63; Rf = 0.38 (CH3OH); IR (KBr, cmꢀ1
/ ) v: 3333, 3322, 3063,
3030, 2946, 2922, 2895, 2844, 2754, 1953, 1582, 1256, 1102,
1
703; H NMR (d ppm): 7.38–7.16 (m, 5H, H-20 H-60); 7.01 (dd,
J = 8.1, J = 7.6, 1H, H-5); 6.75 (d, J = 8.1, 1H, H-6); 6.73 (d, J = 7.6,
1H, H-4), 5.24 (br s, 1H, –OH); 4.62 (t, J = 6.5, 1H, CH); 3.97 (t,
J = 6.3, 2H, Ar–O–CH2–); 2.72 (t, J = 6.9, 2H, –CH2–N); 2.64 (d,