Molecules 2020, 25, 4107
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7-(3-(4-(2-Methoxyphenyl)piperazin-1-yl)propoxy)spiro[chromane-2,10-cyclohexan]-4-one (9e). Pale-white
solid; m. p. 105–107 ◦C; yield 71.4%; 1H-NMR (CDCl3)
7.79 (d, J = 8.0 Hz, 1H), 6.85–7.00 (m, 4H),
δ
6.56–6.53 (m, 1H), 6.44 (d, J = 4.0 Hz, 1H), 4.09 (t, J = 8.0 Hz, 2H), 3.87 (s, 3H), 3.12 (m, 4H), 2.70 (s, br,
4H), 2.64 (s, 2H), 2.60 (t, J = 8.0 Hz, 2H), 2.07-1.97 (m, 4H), 1.72-1.66 (m, 2H), 1.52-1.45 (m, 4H), 1.34–1.30
(s, 2H). HRMS (ESI) calculated for C28H37N2O4 [M + H]+, 465.2748; found, 465.2740.
7-(3-(4-(2-(Trifluoromethyl)phenyl)piperazin-1-yl)propoxy)spiro[chromane-2,10-cyclohexan]-4-one
Off-white solid; m. p. 138–140 ◦C; yield 74.7%; 1H-NMR (CDCl3)
7.80–7.73 (m, 1H), 7.42–7.34 (m,
(9f).
δ
1H), 7.19–7.06 (m, 3H), 6.56–6.52 (m, 1H), 6.41 (d, J = 4.0 Hz, 1H), 4.05 (t, J = 8.0 Hz, 2H), 3.31-3.28 (m,
2H), 2.70–2.52 (m, 6H), 2.30–2.05 (m, 4H), 1.99–1.48 (m, 10H), 1.36–1.32 (m, 2H). HRMS (ESI) calculated
for C28H34F3N2O3 [M + H]+, 503.2516; found, 503.2511.
7-(3-(4-(6-Fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)propoxy)spiro[chromane-2,10-cyclohexan]-4-one (9g).
Pale-white solid; m. p. 96–98 ◦C; yield 67.1%; 1H-NMR (CDCl3)
δ 7.79(d, J = 8.0 Hz, 1H), 7.74–7.70
(m, 1H), 7.26–7.24 (m, 1H), 7.10–7.05 (m, 1H), 6.58-6.55 (m, 1H), 6.45 (d, J = 4.0 Hz, 1H), 4.11 (t, J = 8.0
Hz, 2H), 3.12–3.10 (m, 3H), 2.66 (s, 2H), 2.61 (t, J = 8.0 Hz, 2H), 2.2–1.98 (m, 12H), 1.74–1.48 (m, 4H),
1.36-1.33 (m, 2H). HRMS (ESI) calculated for C29H34FN2O4 [M + H]+, 493.2497; found, 493.2495.
7-(4-(4-(6-Fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)butoxy)spiro[chromane-2,10-cyclohexan]-4-one
White solid; m. p. 126–128 ◦C; yield 72.9%; 1H-NMR (CDCl3)
7.78(d, J = 8.0 Hz, 1H), 7.70–7.73 (m,
(9h).
δ
1H), 7.26–7.24 (m, 1H), 7.09–7.04 (m, 1H), 6.55–6.52 (m, 1H), 6.42 (d, J = 4.0 Hz, 1H), 4.05 (t, J = 8.0
Hz, 2H), 3.13-3.06 (m, 3H), 2.65 (s, 2H), 2.49(t, J = 8.0 Hz, 2H), 2.18-1.98 (m, 8H), 1.86-1.84 (m, 2H),
1.75-1.69 (m, 4H), 1.53-1.50 (m, 4H), 1.37-1.31 (m, 2H). HRMS (ESI) calculated for C30H36FN2O4 [M +
H]+, 507.2654; found, 507.6259.
7-(4-(4-(2,3-Dimethylphenyl)piperazin-1-yl)butoxy)spiro[chromane-2,10-cyclohexan]-4-one (9i). White solid;
◦
1
m. p. 138–140 C; yield 74.3%; H-NMR (CDCl3)
δ 7.81–7.76 (m, 1H), 7.10–6.92(m, 3H), 6.56–6.52
(m, 1H), 6.42 (d, J = 4.0 Hz, 1H), 4.06(t, J = 8.0 Hz, 2H), 3.06 (s, br, 4H), 2.66 (s, 2H), 2.60 (t, J = 8.0
Hz, 2H), 2.29 (s, 3H), 2.23 (s, 3H), 2.07–1.48 (m, 16H), 1.37–1.31 (m, 2H).HRMS (ESI) calculated for
C30H41N2O3 [M + H]+,477.3112; found, 477.3110.
7-(4-(4-(2,3-Dichlorophenyl)piperazin-1-yl)butoxy)spiro[chromane-2,10-cyclohexan]-4-one(9j). White solid; m.
p. 119–121 ◦C; yield 70.7%; 1H-NMR (CDCl3)
δ 7.81–7.76(m, 1H), 7.10–6.92 (m, 3H), 6.56–6.52 (m, 1H),
6.42 (d, J = 4.0 Hz, 1H), 4.06 (t, J = 8.0 Hz, 2H), 3.00 (s, br, 4H), 2.66 (s, 2H), 2.54(t, J = 8.0 Hz, 3H), 2.29
(s, 3H), 2.01-1.48 (m, 12H), 1.37–1.33 (m, 2H). HRMS (ESI) calculated for C28H35Cl2N2O3 [M + H]+,
517.2019; found, 517.2013.
7-(4-(4-(Benzo[d]isothiazol-3-yl)piperidin-1-yl)butoxy)spiro[chromane-2,10-cyclohexan]-4-one (9k). Pale-white
solid; m. p. 129–130 ◦C; yield 62.8%; 1H-NMR (CDCl3)
δ 7.79 (d, J = 8.0 Hz, 2H), 7.19–7.16 (m, 2H),
7.49–7.45 (m, 1H), 6.99–6.96 (m, 1H), 6.56–6.53 (m, 1H), 6.42 (d, J = 4.0 Hz, 1H), 4.05 (t, J = 8.0 Hz, 2H),
3.11(s, br, 4H), 2.70 (s, br, 4H), 2.66(s, 2H), 2.52 (t, J = 8.0 Hz, 2H), 2.00-1.48 (m, 12H), 1.34-1.31 (m, 2H).
HRMS (ESI) calculated for C30H37N2O3S[M + H]+, 505.2519; found, 505.2514.
7-(4-(4-(6-Fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)butoxy)chroman-4-one (13a). Colorless oily liquid;
yield 58.1%; 1H-NMR (CDCl3)
δ 7.80(d, J = 8.0 Hz, 1H), 7.75–7.71 (m, 1H), 7.26–7.24 (m, 1H), 7.11–7.06
(m, 1H), 6.56–6.53 (m, 1H), 6.38 (d, J = 4.0 Hz, 1H), 4.42 (t, J = 8.0 Hz, 2H), 4.06 (t, J = 8.0 Hz, 2H),3.06–2.95
(m, 4H), 2.81–2.78 (m, 1H), 2.52–2.43 (m, 4H), 1.92–1.69 (m, 6H), 1.41-1.35 (m, 2H). HRMS (ESI) calculated
for C25H28FN2O4 [M + H]+, 439.2018; found, 439.2017.
7-(4-(4-(6-Fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)butoxy)-5-methylchroman-4-one (13b). Pale-white solid;
m. p. 85–87 ◦C; yield 63.6%; 1H-NMR (CDCl3)
δ 7.75–7.71 (m, 1H), 7.25–7.23 (m, 1H), 7.06–7.11 (m,
1H), 6.54–6.57 (m, 1H), 6.39 (d, J = 4.0 Hz, 1H), 4.45 (t, J = 8.0 Hz, 2H), 4.07 (t, J = 8.0 Hz, 2H), 3.07–2.96
(m, 4H), 2.80–2.77 (m, 1H), 2.52–2.43 (m, 4H), 2.39 (s, 3H), 1.91–1.67 (m, 6H), 1.40–1.33 (m, 2H). HRMS
(ESI) calculated for C26H30FN2O4 [M + H]+, 453.2184; found, 453.2182.