89
Synthesis of potential inhibitors of oestrone sulphatase
.
¯
. ¯ . .
6 94 (2H, d, J 8 Hz, ArH), 7 11 (1H, broad s, OH), 4 30
(8H, m, (CH2)4CH3), 0 89 (3H, t, J 7 Hz, CH3).
.
c
.
.
.
.
¯
.
.
(CDCl3): 165 8 (C?O), 153 3, 131 5, 129 3, 122 0 (CAr), (2H, t, J 6 Hz, OCH2), 1 76 (2H, m, OCH2CH2), 1 36
.
.
.
.
.
¯
65 7 (OCH2), 31 7 (OCH2CH2), 28 9 (O(CH2)2CH2), 28 6 (12H, m, -(CH2)6CH3), 0 88 (3H, t, J 7 Hz, CH3).
.
c
.
.
.
.
.
.
(O(CH2)3CH2), 26 0 (O(CH2)4CH2), 22 6 (O(CH2 )5CH2), (CDCl3): 167 7 (C?O), 161 0, 132 0, 121 9, 115 4 (CAr),
+
14 1 (CH3 ). MS m z 333 (MNH4 ).
}
.
. . . .
65 4 (OCH2), 32 4 (OCH2CH2), 29 5 (O(CH2)2CH2) 29 3
.
(O(CH2)3CH2), 28 7 (O(CH2)4CH2), 26 0 (O(CH2 )5CH2),
25 7 (O(CH2)6CH2), 22 7 (O(CH2)7CH2), 14 1 (CH3).
.
.
.
.
+
}
GCMS tR 18 406 m z 264 (M ).
Octyl 4-hydroxybenzoate (15)
.
15
Compound was synthesized following the same proce-
dures as for except that conc. H2SO4 (0 3 mL) was added
7
to 4-hydroxybenzoic acid (1 g, 7 24 mmol) and octanol
.
Nonyl 4-[(aminosulphonyl)oxy]benzoate (18)
.
(1 2 mL, 7 6 mmol) in toluene (50 mL). The crude oil was Compound
.
.
puri®ed using ¯ ash chromatography to give as a clear oil dures as for except that NaH (60% dispersion in mineral
18
was synthesized following the same proce-
2
15
(1 05 g, 58 0% ) (Rf 0 61 diethyl ether petroleum ether oil, 0 2 g, 5 mmol) was added to a stirred solution of
}
.
40±60 C (50 50)).
.
.
.
(0 5 g, 1 90 mmol) in DMF (10 mL). Aminosulphonyl
17
}
(®lm) cm : 3349 7 (OH) 2924 7, 2854 5 (CH), chloride in toluene (10 mL,
°
.
.
1
-
C
.
.
.
10 mmol) was added after
(max.)
.
. ¯
(CDCl3):7 94 (2H, d, J 8 Hz, ArH), 30 min. Removal of the solvent under vacuum yielded a
1684 2 (C?O).
H
.
6 89 (2H, d, J 8 Hz, ArH), 6 09 (1H, broad s, OH), 4 29 yellow oil, which was puri®ed using ¯ ash chromatography
(2H, t, J 6 Hz, OCH2), 1 75 (2H, m, OCH2CH2), 1 36 to give (0 07 g, 10 7% ) as a white solid (mp 58±61 C; Rf
¯
.
.
¯
.
.
18
.
.
°
} }
. °
0 24 diethyl ether petroleum ether 40±60 C (30 70)).
.
¯
.
(10H, m, -(CH2)5CH3), 0 85 (3H, t, J 7 Hz, CH3).
.
c
1
-
.
.
.
. . .
(®lm) cm : 3362 3, 3264 2 (NH2), 1704 3 (C?O),
(CDCl3):166 9 (C?O), 160 1, 132 0, 123 0, 115 3 (CAr),
(max.)
.
.
.
.
.
.
.
¯
65 2 (OCH2), 31 9 (OCH2CH2), 29 8 (O(CH2)2CH2) 29 3 1391 8, 1181 8 (S?O). H (CDCl3): 8 02 (2H, d, J 9 Hz,
.
.
.
¯
(O(CH2)3CH2), 28 9 (O(CH2)4CH2), 26 2 (O(CH2 )5CH2), ArH), 7 38 (2H, d, J 9 Hz, ArH), 5 46 (2H, s, NH2), 4 28
27 8 (O(CH2)6CH2), 14 2 (CH3). GCMS tR 17 206 m z 250 (2H, t, J 6 Hz, OCH2), 1 74 (2H, m, OCH2CH2), 1 31
.
.
}
.
.
.
¯
.
.
+
. ¯
(12H, m, (CH2)6CH3), 0 88 (3H, t, J 7 Hz, CH3 ).
(CDCl3): 165 7 (C?O), 153 3, 131 5, 129 2, 122 0 (CAr),
(M ).
c
.
.
.
.
.
.
65 7 (OCH2), 31 8 (OCH2CH2), 29 5 (O(CH2)2CH2), 29 3
(O(CH2)3CH2), 29 2 (O(CH2)4CH2), 28 6 (O(CH2 )5CH2),
.
.
.
Octyl 4-[(aminosulphonyl)oxy]benzoate (16)
.
.
.
}
.
.
26 0 (O(CH2)6CH2), 22 7 (O(CH2)7CH2), 14 1 (CH3). MS
m z found : MNH4 361 1805, (C16H25NO5S)NH4 requires
16
2
Compound
was synthesized following the same proce-
dures as for except that NaH (60% dispersion in mineral
+
+
.
.
361 1797.
.
oil, 0 5 g, 12 5 mmol) was added to a stirred solution of
(2 38 g, 9 52 mmol) in DMF (10 mL). Aminosulphonyl
.
15
.
.
C
chloride in toluene (20 mL,
30 min. Removal of the solvent under vacuum yielded a
20 mmol) was added after
Decyl 4-hydroxybenzoate (19)
19
yellow oil, which was puri®ed using ¯ ash chromatography Compound
was synthesized following the same proce-
.
16
.
.
°
to give (1 01 g, 32 2% ) as a white solid (mp 62±64 C; Rf dures as for except that conc. H2SO4 (0 5 mL) was added
0 45 diethyl ether petroleum ether 40±60 C (50 50)).
7
}
-
}
.
.
°
.
to 4-hydroxybenzoic acid (2 g, 14 5 mmol) and decanol
1
.
.
.
.
(®lm) cm : 3364 3, 3267 7 (NH2), 1704 2 (C?O), (2 8 mL, 14 7 mmol) in toluene (50 mL). The crude oil was
(max.)
.
.
.
¯
19
1391 2, 1157 0 (S?O). H (CDCl3): 7 99 (2H, d, J 9 Hz, puri®ed using ¯ ash chromatography to give as a white
}
.
¯
.
.
.
.
°
.
ArH), 7 35 (2H, d, J 9 Hz, ArH), 5 16 (2H, s, NH2), 4 26 solid (1 06 g, 26 3% ) (mp 30±34 C; Rf 0 57 diethyl ether
}
¯
.
.
(2H, t, J 7 Hz, OCH2), 1 73 (2H, m, OCH2CH2), 1 35 petroleum ether 40±60 C (50 50)).
(10H, m, (CH2)5CH3), 0 87 (3H, t, J 7 Hz, CH3 ).
°
1
-
.
¯
. . .
(®lm) cm : 3354 7 (OH) 2924 2, 2854 1 (CH),
c
(max.)
.
.
.
.
.
.
.
¯
.
(CDCl3): 165 9 (C?O), 153 4, 131 5, 129 1, 122 0 (CAr), 1683 7 (C?O). H (CDCl3): 7 94 (2H, J 8 Hz, ArH), 6 93
.
65 7 (OCH2), 31 8 (OCH2CH2), 29 0 (O(CH2)2CH2), 28 6 (2H, d, J 8 Hz, ArH), 6 37 (1H, broad s, OH), 4 30 (2H,
(O(CH2)3CH2), 26 0 (O(CH2)4CH2), 25 4 (O(CH2 )5CH2), t, J 6 Hz, OCH2), 1 76 (2H, m, OCH2CH2), 1 36 (14H, m,
.
.
.
.
¯
.
.
.
¯
.
.
+
22 6 (O(CH2)6CH2), 14 1 (CH3). MS m z 347 (MNH4 ).
}
.
.
. ¯ .
-(CH2)7CH3 ), 0 88 (3H, t, J 7 Hz, CH3). c (CDCl3): 167 5
.
.
.
.
.
.
.
(C?O), 160 7, 131 9, 122 2, 115 3 (CAr), 65 3, 31 9, 29 5,
.
29 3, 28 7, 26 0, 22 7, 14 1 (only 8 aliphatic carbons visible).
GCMS tR 19 195 m z 278 (M ).
.
.
.
.
+
}
Nonyl 4-hydroxybenzoate (17)
.
17
Compound was synthesized following the same proce-
dures as for except that conc. H2SO4 (0 5 mL) was added
7
to 4-hydroxybenzoic acid (2 g, 14 5 mmol) and nonanol
.
Decyl 4-[(aminosulphonyl)oxy]benzoate (20)
.
(2 5 mL, 14 4 mmol) in toluene (50 mL). The crude oil was Compound
.
puri®ed using ¯ ash chromatography to give as a clear oil dures as for except that NaH (60% dispersion in mineral
.
20
was synthesized following the same proce-
2
17
(0 95 g, 24 8% ) (Rf 0 57 diethyl ether petroleum ether oil, 0 1 g, 2 5 mmol) was added to a stirred solution of
}
.
.
40±60 C (50 50)).
.
.
.
19
(0 5 g, 1 8 mmol) in DMF (10 mL). Aminosulphonyl
}
(®lm) cm : 3352 2 (OH) 2926 6, 2855 8 (CH), chloride in toluene (10 mL,
°
.
.
1
-
C
.
.
.
10 mmol) was added after
(max.)
.
. ¯
(CDCl3): 7 93 (2H, d, J 8 Hz, ArH), 30 min. Removal of the solvent under vacuum yielded a
1682 3 (C?O).
H