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4.1.97. (2S)-1-{[(2S,4R)-4-(3-Hydroxyphenyl)-2-pyrrolid-
inyl]carbonyl}-2-pyrrolidinecarbonitrile 4-methylbenzene-
sulfonate (15). Compound 15 was obtained as a white
powder in 87% yield from 41c according to the same
procedure as described for the preparation of 5 from
35a. TLC Rf = 0.20 (CH2Cl2/MeOH, 9/1); MS (MAL-
DI, pos.) m/z 286 (M+H)+; IR (KBr) 3165, 2243,
1661, 1601, 1589, 1454, 1161, 1122, 1033, 1009, 682,
4.86 (dd, J = 7.8, 4.8 Hz, 1H), 6.21 (d, J = 2.2 Hz, 1H),
6.27 (d, J = 2.2 Hz, 1H), 8.64 (s, 1H), 9.39 (s, 1H),
10.15 (s, 1H); Anal. Calcd for C18H24N3O3: C, 59.09;
H, 6.61; N, 11.49. Found: C, 58.79; H, 6.68; N, 11.03.
4.1.101. (2S)-1-{[(2S,4R)-4-(4-Hydroxy-2,6-dimethoxy-
phenyl)-2-pyrrolidinyl]carbonyl}-2-pyrrolidinecarbonitrile
4-methylbenzenesulfonate (19). Compound 19 was ob-
tained as a beige powder in 100% yield from 41g accord-
ing to the same procedure as described for the
preparation of 5 from 35a. TLC Rf = 0.43 (CH2Cl2/
MeOH, 5/1); MS (APCI, pos. 20 V) m/z 346 (M+H)+;
IR (KBr) 3194, 2245, 1662, 1615, 1600, 1196, 1153,
1
568 cmꢀ1; H NMR (300 MHz, DMSO-d6) d 1.65–1.87
(m, 1H), 1.95–2.09 (m, 2H), 2.09–2.26 (m, 2H), 2.28 (s,
3H), 2.82–3.04 (m, 1H) 3.08–3.31 (m, 1H), 3.45–3.55
(m, 1H), 3.56–3.74 (m, 3H), 4.51–4.69 (m, 1H), 4.85
(dd, J = 7.7, 4.8 Hz, 1H), 6.61–6.81 (m, 3H), 7.06–7.19
(m, 3H), 7.46 (d, J = 8.0 Hz, 2H), 8.78–9.05 (m, 1H),
9.31–9.63 (m, 2H); HRMS (FAB) calcd for
C16H20N3O2: 286.1556. Found: 286.1554.
1121, 1033, 1009, 682 cmꢀ1
;
1H NMR (300 MHz,
DMSO-d6) d 1.91–2.06 (m, 2H), 2.07–2.33 (m, 3H),
2.28 (s, 3H), 2.45–2.62 (m, 1H), 3.19–3.81 (m, 4H),
3.69 (s, 6H), 3.86–4.08 (m, 1H), 4.49–4.72 (m, 1H),
4.85 (dd, J = 8.0, 4.7 Hz, 1H), 6.07 (s, 2H), 7.10 (d,
J = 8.0 Hz, 2H), 7.46 (d, J = 8.0 Hz, 2H), 8.67 (s, 1H),
9.33 (s, 1H), 9.56 (s, 1H); HRMS (FAB) calcd for
C18H24N3O4: 346.1767. Found: 346.1768.
4.1.98. (2S)-1-{[(2S,4R)-4-(4-Hydroxyphenyl)-2-pyrrolid-
inyl]carbonyl}-2-pyrrolidinecarbonitrile 4-methylbenzene-
sulfonate (16). Compound 16 was obtained as an ivory
powder in 92% yield from 41d according to the same
procedure as described for the preparation of 5 from
35a. TLC Rf = 0.25 (CHCl3/MeOH, 2/1); MS (APCI,
pos. 20 V) m/z 286 (M+H)+; IR (KBr) 3290, 2242,
1660, 1615, 1519, 1449, 1213, 1164, 1122, 1009,
4.1.102. (2S)-1-{[(2S,4R)-4-(2-Ethyl-4-hydroxy-6-methyl-
phenyl)-2-pyrrolidinyl]carbonyl}-2-pyrrolidinecarbonitrile
4-methylbenzenesulfonate (20). Compound 20 was ob-
tained as a pale pink powder in 85% yield from 41h
according to the same procedure as described for the
preparation of 5 from 35a. TLC Rf = 0.25 (CHCl3/
MeOH, 5/1); MS (APCI, neg. 20 V) m/z 326 (MꢀH)ꢀ;
IR (KBr) 3377, 2967, 2245, 1661, 1611, 1454, 1146,
1
684 cmꢀ1; H NMR (300 MHz, DMSO-d6) d 1.62–1.84
(m, 1H), 1.92–2.08 (m, 2H), 2.09–2.27 (m, 2H), 2.28 (s,
3H), 2.80–2.97 (m, 1H), 3.06–3.22 (m, 1H), 3.35–3.53
(m, 2H), 3.55–3.70 (m, 2H), 4.47–4.68 (m, 1H), 4.85
(dd, J = 7.8, 4.7 Hz, 1H), 6.72 (d, J = 8.0 Hz, 2H), 7.11
(dd, J = 8.2, 2.9 Hz, 4H), 7.47 (d, J = 8.0 Hz, 2H),
8.69–9.12 (m, 1H), 9.27–9.60 (m, 2H); HRMS (FAB)
calcd for C16H20N3O2: 286.1556. Found: 286.1558.
1123, 1033, 1009, 682 cmꢀ1
;
1H NMR (300 MHz,
DMSO-d6) d 1.07–1.15 (m, 3H), 1.94–2.09 (m, 2H),
2.10–2.32 (m, 3H), 2.23 (s, 3H), 2.28 (s, 3H), 2.44–2.58
(m, 2H), 2.63–2.80 (m, 1H), 3.30–3.50 (m, 2H), 3.51–
3.72 (m, 2H), 3.64 (s, 1H), 3.78–3.95 (m, 1H), 4.61–
4.75 (m, 1H), 4.86 (dd, J = 7.6, 4.7 Hz, 1H), 6.40–6.47
(m, 2H), 7.10 (d, J = 8.0 Hz, 2H), 7.46 (d, J = 8.0 Hz,
2H), 9.05 (s, 1H), 9.42 (s, 1H); HRMS (FAB) calcd
for C19H26N3O2: 328.2025. Found: 328.2023.
4.1.99. (2S)-1-{[(2S,4R)-4-(4-Hydroxy-2,6-dimethylphe-
nyl)-2-pyrrolidinyl]carbonyl}-2-pyrrolidinecarbonitrile 4-
methylbenzenesulfonate (17). Compound 17 was ob-
tained as an ivory powder in 100% yield from 41n
according to the same procedure as described for the
preparation of 5 from 35a. TLC Rf = 0.25 (CHCl3/
MeOH, 5/1); MS (APCI, pos. 20 V) m/z 314 (M+H)+;
IR (KBr) 3169, 2243, 1662, 1611, 1593, 1453, 1150,
4.1.103. (2S)-1-{[(2S,4R)-4-(2,6-Diethoxy-4-hydroxyphe-
nyl)-2-pyrrolidinyl]carbonyl}-2-pyrrolidinecarbonitrile 4-
methylbenzenesulfonate (21). Compound 21 was
obtained as a white powder in 93% yield from 41i
according to the same procedure as described for the
preparation of 5 from 35a. TLC Rf = 0.36 (CHCl3/
MeOH, 5/1); MS (APCI, pos. 20 V) m/z 374 (M+H)+;
IR (KBr) 3186, 2978, 2243, 1662, 1599, 1461, 1159,
1
1122, 1033, 1009, 682, 568 cmꢀ1; H NMR (300 MHz,
DMSO-d6) d 1.95–2.22 (m, 5H), 2.23 (s, 6H), 2.28 (s,
3H), 2.61–2.80 (m, 1H), 3.34–3.66 (m, 4H), 3.75–3.97
(m, 1H), 4.54–4.74 (m, 1H), 4.86 (dd, J = 7.8, 4.7 Hz,
1H), 6.42 (s, 2H), 7.07–7.13 (m, 2H), 7.46 (d,
J = 8.0 Hz, 2H), 9.00 (s, 1H), 9.18 (s, 1H), 9.41 (s,
1H); HRMS (FAB) calcd for C18H24N3O2: 314.1869.
Found: 314.187.
1121, 1033, 1009, 682 cmꢀ1
;
1H NMR (300 MHz,
DMSO-d6) d 1.22–1.37 (m, 6H), 1.91–2.32 (m, 4H),
2.28 (s, 3H), 2.36–2.66 (m, 2H), 3.15–3.82 (m, 5H),
3.82–4.04 (m, 4H), 4.53–4.69 (m, 1H), 4.73–4.90 (m,
1H), 6.00–6.08 (m, 2H), 7.10 (d, J = 8.0 Hz, 2H), 7.46
(d, J = 8.0 Hz, 2H), 8.67 (s, 1H), 9.35 (s, 1H), 9.48 (s,
1H); HRMS (FAB) calcd for C20H28N3O4: 374.208.
Found: 374.2082.
4.1.100.
(2S)-1-{[(2S,4R)-4-(4-Hydroxy-2-methoxy-6-
methylphenyl)-2-pyrrolidinyl]carbonyl}-2-pyrrolidinecar-
bonitrile hydrochloride (18). Compound 18 was obtained
as a white powder in 69% yield from 41f according to
the same procedure as described for the preparation of
12 from 26b. TLC Rf = 0.19 (CHCl3/MeOH, 9/1); MS
(EI, pos.) m/z 329 (M+H)+; IR (KBr) 3129, 2939,
2237, 1644, 1618, 1609, 1586, 1455, 1381, 1371,
4.1.104. (2S)-1-{[(2S,4R)-4-(3-Hydroxy-2,6-dimethylphe-
nyl)-2-pyrrolidinyl]carbonyl}-2-pyrrolidinecarbonitrile 4-
methylbenzenesulfonate (22). Compound 22 was
obtained as a white powder in 92% yield from 41j
according to the same procedure as described for the
preparation of 5 from 35a. TLC Rf = 0.28 (CHCl3/
1155 cmꢀ1 1H NMR (300 MHz, DMSO-d6) d 1.93–
;
2.07 (m, 2H), 2.20 (s, 3H), 2.07–2.34 (m, 3H), 2.53–
2.67 (m, 1H), 3.25–3.40 (m, 1H), 3.44–3.64 (m, 3H),
3.68 (s, 3H), 3.64–3.81 (m, 1H), 4.49–4.64 (m, 1H),