K.R. Francisco, C. Varricchio, T.J. Paniak et al.
European Journal of Medicinal Chemistry 218 (2021) 113399
7.21e7.15 (m, 1H), 7.00e6.91 (m, 2H), 5.01 (s, 1H), 4.61 (d, J ¼ 7.0 Hz,
2H), 4.35 (d, J ¼ 7.0 Hz, 2H), 2.47e2.40 (m, 2H), 2.36e2.29 (m, 2H)
38.00, 37.68, 29.70 ppm. HRMS (ESþ) calculated for C13H20N2O2S2
[M þ Na]þ 323.0858, found 323.0861. IR (neat)
n 2923.28, 2853.49,
ppm. 13C NMR (150 MHz, CDCl3)
d
142.02, 140.70, 133.13, 129.51,
1453.49, 1323.19, 1143.97, 1033.10, 1054.35 cmꢀ1
.
129.48, 128.38, 127.01, 126.28, 81.28, 59.25, 38.37, 29.85 ppm. HRMS
cis-N-(1-Oxido-3-phenethylthietan-3-yl)meth-
(ESþ) calculated for C17H19NO3S [M þ Na]þ 340.0978, found
anesulfonamide (21). Following the same procedure described for
the synthesis of 18, using of cis-3-amino-3-phenethylthietane 1-
oxide 38 (0.030 g, 0.140 mmol, 1.00 eq), Et3N (0.04 g,
0.430 mmol, 3.00 eq) and methanesulfonyl chloride (0.049 g,
0.043 mmol, 3.00 eq). Purification by reverse phase HPLC (10%e90%
CH3CN in H2O) provided the title compound (0.028 g, 0.097 mmol,
340.0975. IR (neat)
n 3115.92, 2981.87, 1444.04, 1320.06, 1147.53,
1092.66 cmꢀ1
.
N,N-Dimethyl-[3-(2-phenylethyl)oxetane-3-yl]sulfamoyl-
amine (17). Following the same procedure described for the syn-
thesis of 15, using (S)-2-methyl-N-(3-phenethyloxetan-3-yl)pro-
pane-2-sulfinamide 40 (0.173 g, 0.976 mmol, 1.00 eq),
dimethylsulfamoyl chloride (0.280 g, 1.95 mmol, 2.00 eq), and Et3N
(0.198 g, 1.95 mmol, 2.00 eq). Purification by silica gel column
chromatography (up to 20% EtOAc in hexane) provided the title
compound (0.098 g, 0.340 mmol, 35%). 1H NMR (600 MHz, CDCl3)
68%). 1H NMR (600 MHz, CDCl3)
d
7.31 (t, J ¼ 7.5 Hz, 2H), 7.23 (t,
J ¼ 7.3 Hz, 1H), 7.19 (d, J ¼ 7.5 Hz, 2H), 5.44 (s, 1H), 3.97e3.88 (m,
2H), 3.70e3.59 (m, 2H), 3.08 (s, 3H), 2.77e2.68 (m, 2H), 2.07 (dd,
J ¼ 10.1, 6.4 Hz, 2H) ppm. 13C NMR (150 MHz, CDCl3)
d 139.77,
128.97, 128.39, 126.78, 62.78, 51.54, 44.75, 42.53, 29.97 ppm. HRMS
d
7.31 (t, J ¼ 7.7 Hz, 2H), 7.22 (d, J ¼ 6.8 Hz, 3H), 4.74 (d, J ¼ 7.0 Hz,
2H), 4.45 (d, J ¼ 6.8 Hz, 2H), 4.38 (s, 1H), 2.86 (s, 6H), 2.75e2.70 (m,
2H), 2.43e2.35 (m, 2H) ppm. 13C NMR (150 MHz, CDCl3)
140.98,
(ESþ) calculated for C12H17NO3S2 [M þ Na]þ 310.0542, found
310.0542. IR (neat)
n 3125.00, 2862.28, 1465.89, 1310.97, 1033.39,
d
1022.67 cmꢀ1
.
128.78, 128.46, 126.41, 81.08, 59.23, 38.43, 38.01, 30.01 ppm. HRMS
cis-N-(1-Oxido-3-phenethylthietan-3-yl)benzenesulfona-
mide (22). Following the same procedure described for the syn-
thesis of 18, using of cis-3-amino-3-phenethylthietane 1-oxide 38
(0.030 g, 0.133 mmol, 1.00 eq), Et3N (0.040 g, 0.400 mmol, 3.00 eq)
and benzenesulfonyl chloride (0.071 g, 0.400 mmol, 3.00 eq). Pu-
rification by reverse phase HPLC (10%e90% CH3CN in H2O) provided
the title compound (0.034 g, 0.093 mmol, 70%). 1H NMR (600 MHz,
(ESþ) calculated for C13H20N2O3S [M þ H]þ 285.1267, found
285.1268. IR (neat)
n 2923.70, 1455.67, 1326.43, 1144.23, 1050.98,
1033.09 cmꢀ1
.
N-(3-Phenethylthietan-3-yl)methanesulfonamide (18). To a
solution of 3-phenethylthietan-3-amine 43 (0.245 g, 1.27 mmol,
1.00 eq) in anh. CH2Cl2 (5.0 mL), Et3N (0.256 g, 2.53 mmol, 2.00 eq)
was added, followed by methanesulfonyl chloride (0.290 g,
2.53 mmol, 2.00 eq) at 0 ꢁC under N2. The reaction mixture was
stirred at rt overnight. H2O was added, and the crude was extracted
with EtOAc ( ꢂ 3). The combined organic extracts were dried over
Na2SO4, filtered, and concentrated in vacuo. Purification by silica gel
column chromatography (up to 30% of EtOAc in hexane) provided
the title compound (0.118 g, 0.435 mmol, 34%). 1H NMR (600 MHz,
CDCl3)
d
7.93 (d, J ¼ 7.9 Hz, 2H), 7.64 (t, J ¼ 7.5, 1H), 7.56 (t, J ¼ 7.7 Hz,
2H), 7.28 (s, 1H), 7.20 (t, J ¼ 7.4 Hz, 2H), 7.02 (d, J ¼ 7.7 Hz, 2H), 5.02
(s, 1H), 3.78e3.70 (m, 2H), 3.39e3.33 (m, 2H), 2.60e2.54 (m, 2H),
2.00e1.94 (m, 2H) ppm. 13C NMR (150 MHz, CDCl3)
d 141.73, 139.79,
133.53, 129.71, 128.85, 128.39, 127.22, 126.67, 62.90, 51.09, 42.57,
29.78 ppm. HRMS (ESe) calculated for C17H19NO3S2 [M þ Na]þ
372.0699, found 372.0700.
CDCl3)
d
7.32 (t, J ¼ 7.6 Hz, 2H), 7.24 (d, J ¼ 7.2 Hz, 3H), 4.66 (s, 1H),
cis-3-[(Dimethylsulfamoyl)amino]-3-(2-phenylethyl)-
1lambda4-thietan-1-one (23). Following the same procedure
described for the synthesis of 18, using of cis-3-amino-3-
phenethylthietane 1-oxide 38 (0.060 g, 0.290 mmol, 1.00 eq),
Et3N (0.087 g, 0.860 mmol, 3.00 eq) and dimethylsulfamoyl chlo-
ride (0.120 g, 0.860 mmol, 3.00 eq). Purification by reverse phase
HPLC (10%e90% CH3CN in H2O) provided the title compound
3.66 (d, J ¼ 9.9 Hz, 2H), 3.14 (d, J ¼ 10.1 Hz, 2H), 3.08 (s, 3H), 2.76
(dd, J ¼ 10.4, 6.5 Hz, 2H), 2.49 (dd, J ¼ 10.3, 6.6 Hz, 2H) ppm. 13
C
NMR (150 MHz, CDCl3)
d 140.75, 128.86, 128.48, 126.49, 63.28,
44.79, 39.95, 38.16, 29.85 ppm. HRMS (ESþ) calculated for
C
12H17NO2S2 [M þ Na]þ 294.0593, found 294.0592. IR (neat)
n
3234.79, 2967.55, 1732.48, 1442.63, 1307.46, 1153.47, 1130.11 cmꢀ1
.
N-(3-Phenethylthietan-3-yl)benzenesulfonamide
(19).
(0.014 g, 0.44 mmol, 15%). 1H NMR (600 MHz, CDCl3)
d 7.31 (t,
Following the same procedure described for the synthesis of 18,
using of 3-phenethylthietan-3-amine 43 (0.200 g, 1.03 mmol, 1.00
eq), Et3N (0.209 g, 2.07 mmol, 2.00 eq) and benzenesulfonyl chlo-
ride (0.365 g, 2.07 mmol, 2.00 eq). Purification by silica gel column
chromatography (up to 20% EtOAc in hexane) provided the title
compound (0.270 g, 0.810 mmol, 78%). 1H NMR (600 MHz, CDCl3)
J ¼ 7.5 Hz, 2H), 7.22 (td, J ¼ 7.2, 1.5 Hz,1H), 7.21e7.17 (m, 2H), 4.65 (s,
1H), 3.90e3.82 (m, 2H), 3.64e3.57 (m, 2H), 2.86 (s, 6H), 2.75e2.67
(m, 2H), 2.06e1.99 (m, 2H) ppm. 13C NMR (150 MHz, CDCl3) 140.13,
128.89, 128.44, 126.63, 62.43, 50.98, 42.53, 38.02, 29.83 ppm. HRMS
(ESþ) calculated for C13H20N2O3S2 [M þ Na]þ 339.0808, found
339.0801.
d
7.96e7.90 (m, 2H), 7.64e7.58 (m, 1H), 7.57e7.49 (m, 2H), 7.27 (d,
N-(1,1-Dioxido-3-phenethylthietan-3-yl)meth-
J ¼ 2.0 Hz, 1H), 7.24 (d, J ¼ 2.0 Hz, 1H), 7.22e7.15 (m, 1H), 7.06e6.99
(m, 2H), 4.89 (s, 1H), 3.54e3.48 (m, 2H), 3.02e2.95 (m, 2H),
2.54e2.48 (m, 2H), 2.45e2.40 (m, 2H) ppm. 13C NMR (150 MHz,
anesulfonamide (24). Following the same procedure described for
the synthesis of 18, using of 3-amino-3-phenethylthietane 1,1-
dioxide 46 (0.050 g, 0.220 mmol, 1.00 eq), Et3N (0.067 g,
0.670 mmol, 3.00 eq) and methanesulfonyl chloride (0.076 g,
0.670 mmol, 3.00 eq). Purification by reverse phase HPLC (10%e90%
CH3CN in H2O) provided the title compound (0.043 g, 0.014 mmol,
CDCl3)
d 142.48, 140.93, 133.02, 129.43, 128.56, 126.98, 126.16,
63.00, 39.63, 38.08, 29.60 ppm. HRMS (ESþ) calculated for
C
17H19NO2S2 [M þ Na]þ 356.0749, found 356.0749. IR (neat)
n
3276.99, 2948.31, 1448.03, 1320.15, 1154.08, 1090.87, 1063.51 cmꢀ1
.
64%). 1H NMR (600 MHz, CDCl3)
d
7.31 (t, J ¼ 7.6 Hz, 2H), 7.22 (dd,
N,N-Dimethyl-[3-(2-phenylethyl)thietan-3-yl]sulfamoyl-
amine (20). Following the same procedure described for the syn-
thesis of 18, using of 3-phenethylthietan-3-amine 43 (0.050 g,
0.260 mmol, 1.00 eq), Et3N (0.052 g, 0.520 mmol, 2.00 eq) and
dimethylsulfamoyl chloride (0.074 g, 0.520 mmol, 2.00 eq). Purifi-
cation by silica gel column chromatography (up to 20% EtOAc in
hexane) provided the title compound (0.024 g, 0.080 mmol, 24%).
J ¼ 27.3, 7.3 Hz, 3H), 5.50 (s, 1H), 4.36e4.28 (m, 2H), 4.13e4.07 (m,
2H), 3.13 (s, 3H), 2.84e2.73 (m, 2H), 2.49e2.37 (m, 2H) ppm. 13C
NMR (150 MHz, CDCl3)
d 139.29, 129.06, 128.45, 126.94, 74.73,
48.35, 44.75, 41.64, 30.86 ppm. HRMS (ESe) calculated for
C
12H17NO4S2 [M ꢀ H]e 302.0526, found 302.0526. IR (neat)
n
3275.93, 3028.34, 2924.35, 1455.59, 1315.13, 1232.45, 1143.38,
1090.29 cmꢀ1
.
1H NMR (600 MHz, CDCl3)
d
7.31 (t, J ¼ 7.6 Hz, 2H), 7.25e7.20 (m,
N-(1,1-Dioxido-3-phenethylthietan-3-yl)benzenesulfona-
mide (25). Following the same procedure described for the syn-
thesis of 18, using of 3-amino-3-phenethylthietane 1,1-dioxide 46
(0.030 g, 0.133 mmol, 1.00 eq), Et3N (0.040 g, 0.399 mmol, 3.00 eq)
3H), 4.38 (s, 1H), 3.69 (d, J ¼ 9.9 Hz, 2H), 3.09 (d, J ¼ 10.3 Hz, 2H),
2.84 (s, 6H), 2.74e2.72 (m, 2H), 2.47e2.45 (m, 2H) ppm. 13C NMR
(150 MHz, CDCl3)
d 141.15, 128.73, 128.51, 126.31, 62.92, 39.76,
12