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S. Komoriya et al. / Bioorg. Med. Chem. 13 (2005) 3927–3954
Mp 243–245 ꢁC (decomp.). 1H NMR (400 MHz,
DMSO-d6): d 3.03–3.06 (2H, m), 3.20–3.23 (2H, m),
3.41–3.44 (2H, m), 3.83–3.86 (2H, m), 7.61 (1H, dd,
J = 8.8, 2.0 Hz), 8.10 (1H, d, J = 8.8 Hz), 8.13 (1H, s),
8.30–8.40 (3H, m), 8.90–9.02 (2H, br), 9.40–9.46 (2H,
m). Anal. Calcd for C22H18ClN5O3SÆHClÆ0.7H2O: C,
48.13; H, 3.74; Cl, 12.91; N, 12.75; S, 11.68. Found: C,
47.95; H, 3.78; Cl, 13.13; N, 12.65; S, 11.53. MS (FAB)
m/z 500 [(M+H)+, Cl35], 502 [(M+H)+, Cl37]. IR (ATR)
cmꢀ1 3448, 1637, 1589, 1481, 1419, 1348, 1330, 1191,
1143, 1122, 1054, 998, 946, 852, 829, 802.
Mp 155–160 ꢁC (decomp.). 1H NMR (400 MHz,
DMSO-d6): d 3.10–3.20 (2H, m), 3.20–3.30 (2H, m),
3.50–3.60 (2H, m), 3.85–3.95 (2H, m), 6.97 (1H, s),
7.30–7.52 (5H, m), 7.68 (1H, s), 8.39 (1H, d,
J = 5.9 Hz), 9.28 (2H, s), 9.50 (1H, s). MS (FAB) m/z
499 [(M+H)+, Cl35], 501 [(M+H)+, Cl37]. HRMS
(FAB) Calcd for C22H20ClN6O4S: 499.0955. Found:
499.0943. IR (ATR) cmꢀ1 3118, 2923, 2859, 1643,
1500, 1432, 1415, 1353, 1309, 1276, 1230, 1195, 1155,
1112, 1054, 1014, 950, 890, 844, 809.
6.84. 4-[2-[[4-[(6-Chlorobenzo[b]thien-2-yl)sulfonyl]pip-
erazin-1-yl]carbonyl]pyrimidin-5-yl]pyridine N-oxide
(75a)
6.81. 1-[(6-Chlorobenzo[b]thien-2-yl)sulfonyl]-4-[[5-(pyri-
din-2-yl)pyrimidin-2-yl]carbonyl]piperazine hydrochloride
(74b)
Starting with 74a (140 mg, 0.28 mmol) and following the
procedure for the preparation of 7 gave 75a (yield, 56%)
as a colorless powder.
Starting with 71 (400 mg, 0.80 mmol) and (2-pyr-
idyl)boronic acid (109 mg, 0.88 mmol) and following
the procedure for the preparation of 72a gave 74b (yield,
82%) as a yellow powder.
Mp 233–236 ꢁC (decomp.). 1H NMR (400 MHz,
DMSO-d6): d 3.24 (2H, br), 3.34 (2H, br), 3.60 (2H,
br), 3.98 (2H, br), 7.47 (1H, dd, J = 8.8, 2.0 Hz), 7.52
(2H, d, J = 7.3 Hz), 7.79 (1H, s), 7.83 (1H, d,
J = 8.8 Hz), 7.88 (1H, br s), 8.33 (2H, d, J = 7.3 Hz),
9.00 (2H, s). Anal. Calcd for C22H18ClN5O4SÆ0.4H2O:
C, 50.50; H, 3.62; Cl, 6.78; N, 13.39; S, 12.26. Found:
C, 50.24; H, 3.62; Cl, 7.14; N, 13.19; S, 12.04. MS
(FAB) m/z 516 [(M+H)+, Cl35], 518 [(M+H)+, Cl37].
IR (ATR) cmꢀ1 3018, 1637, 1496, 1484, 1442, 1417,
1351, 1247, 1193, 1155, 1112, 1056, 1043, 1029, 991,
937, 862, 848.
Mp 228–231 ꢁC (decomp.). 1H NMR (400 MHz,
DMSO-d6): d 3.01–3.10 (2H, m), 3.17–3.26 (2H, m),
3.39–3.47 (2H, m), 3.79–3.87 (2H, m), 7.52 (1H, dd,
J = 7.3 and 4.9 Hz), 7.61 (1H, d, J = 8.8 Hz), 8.01 (1H,
dt, J = 1.5 and 7.3 Hz), 8.10 (1H, d, J = 8.8 Hz), 8.12
(1H, s), 8.18 (1H, d, J = 7.3 Hz), 8.35 (1H, s), 8.76
(1H, d, J = 4.9 Hz), 9.48 (2H, s). Anal. Calcd for
C22H18ClN5O3S2ÆHClÆ0.5H2O: C, 48.44; H, 3.70; Cl,
13.00; N, 12.84; S, 11.76. Found: C, 48.53; H, 3.56; Cl,
13.04; N, 12.72; S, 11.85. MS (FAB) m/z 500
[(M+H)+, Cl35], 502 [(M+H)+, Cl37]. IR (ATR) cmꢀ1
3054, 1652, 1621, 1494, 1427, 1353, 1276, 1147, 1120,
1099, 1052, 998, 946, 890, 852, 800.
6.85. 2-[2-[[4-[(6-Chlorobenzo[b]thien-2-yl)sulfonyl]pip-
erazin-1-yl]carbonyl]pyrimidin-5-yl]pyridine N-oxide
(75b)
6.82. 4-[2-[[4-[(5-Chloroindol-2-yl)sulfonyl]piperazin-1-
yl]carbonyl]pyrimidin-5-yl]pyridine N-oxide (73a)
Starting with 74b (164 mg, 0.33 mmol) and following the
procedure for the preparation of 7 gave 75b (yield, 21%)
as a pale yellow powder.
Starting with 72a (536 mg, 1.1 mmol) and following the
procedure for the preparation of 7 gave 73a (yield, 50%)
as a pale yellow amorphous powder.
Mp 271–273 ꢁC. 1H NMR (400 MHz, DMSO-d6): d 3.24
(2H, t, J = 4.9 Hz), 3.33 (2H, t, J = 4.9 Hz), 3.63 (2H, t,
J = 4.9 Hz), 3.99 (2H, t, J = 4.9 Hz), 7.36–7.53 (4H, m),
7.78 (1H, s), 7.84 (1H, d, J = 8.3 Hz), 7.88 (1H, br s),
8.36–8.39 (1H, m), 9.29 (2H, s). Anal. Calcd for
C22H18ClN5O4S2: C, 51.21; H, 3.52; Cl, 6.87; N, 13.57;
S, 12.43. Found: C, 50.91; H, 3.44; Cl, 6.95; N, 13.36;
S, 12.27. MS (FAB) m/z 516 [(M+H)+, Cl35], 518
[(M+H)+, Cl37]. IR (ATR) cmꢀ1 3054, 3029, 1639,
1490, 1432, 1417, 1346, 1322, 1238, 1187, 1147, 1116,
995, 956, 941, 854, 823, 800.
1H NMR (400 MHz, DMSO-d6): d 2.95 (2H, br), 3.15
(2H, br), 3.37 (2H, br), 3.79 (2H, br), 7.05 (1H, s),
7.34 (1H, dd, J = 8.8 and 1.5 Hz), 7.51 (1H, d,
J = 8.8 Hz), 7.80 (1H, d, J = 1.5 Hz), 7.95 (2H, d,
J = 7.3 Hz), 8.37 (2H, d, J = 7.3 Hz), 9.28 (2H, s),
12.47 (1H, s). Anal. Calcd for C22H19ClN6O4SÆ0.5-
H2OÆ0.2EtOH: C, 52.02; H, 4.13; Cl, 6.86; N, 16.25; S,
6.20. Found: C, 52.03; H, 3.99; Cl, 7.18; N, 15.99; S,
6.16. MS (FAB) m/z 499 [(M+H)+, Cl35], 501
[(M+H)+,
Cl37].
HRMS
(FAB)
Calcd
for
C22H20ClN6O4S: 499.0955. Found: 499.0970. IR
(ATR) cmꢀ1 3108, 2921, 2859, 1643, 1498, 1417, 1351,
1307, 1243, 1193, 1182, 1155, 1114, 1054, 950, 890,
846, 809.
6.86. 1,4-Dibenzyl-2-(2-methyl-2-propenyl)piperazine (78)
To a solution of 1,4-dibenzyl-2-ethoxycarbonylpiper-
azine (76) (19.6 g, 58 mmol) in CH2Cl2 (400 mL) was
added diisobutylaluminum hydride (0.95 M in hexane)
(122 mL) at ꢀ78 ꢁC. The reaction mixture was stirred
for 2.5 h, added to saturated aqueous NH4Cl (150 mL)
at ꢀ78 ꢁC, and then warmed up to room temperature.
The separated aqueous layer was extracted with CH2Cl2.
The combined organic layer was washed with H2O,
dried over Na2SO4, and concentrated in vacuo. No fur-
6.83. 2-[2-[[4-[(5-Chloroindol-2-yl)sulfonyl]piperazin-1-
yl]carbonyl]pyrimidin-5-yl]pyridine N-oxide (73b)
Starting with 72b (154 mg, 0.32 mmol) and following the
procedure for the preparation of 7 gave 73b (yield, 20%)
as a pale yellow powder.