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4.1.31. (2S,4S)-1-[(2S)-2-Amino-3-phenylpropanoyl]-4-
fluoropyrrolidine-2-carbonitrile (17a)
4.1.38. tert-Butyl N-[(2S)-1-[(2S,4S)-2-cyano-4-fluoropyrrolidin-
1-yl]-3-(4-nitrophenyl)-1-oxopropan-2-yl]carbamate (16e)
A similar procedure to that described above for 6a gave the de-
sired product 16e. 1H NMR (300 MHz, CDCl3) d 8.12–8.21 (m, 2H),
8.02 (s, 1H), 7.37–7.49 (m, 2H), 5.28–5.30 (m, 1H), 4.60–4.87 (m,
1H), 4.05–4.15 (m, 1H), 3.70–3.95 (m, 1H), 3.29 (dd, J1 = 5.1 Hz,
J2 = 5.1 Hz, 1H), 3.06–4.16 (m, 1H), 2.85–2.99 (m, 1H), 2.57–2.73
(m, 2H). ESI-MS m/z 429, [M+Na]+.
A similar procedure to that described above for 7a gave the de-
sired product 17a. 1H NMR (300 MHz, DMSO-d6) d 7.21–7.30 (m,
5H), 5.19–5.36 (m, 1H), 5.00 (d, J = 8.4 Hz, 1H), 4.19 (q, J = 6.9 Hz,
1H), 3.61–3.78 (m, 1H), 3.16 (dd, J1 = 5.1 Hz, J2 = 5.1 Hz, 1H),
2.93–2.96 (m, 1H), 2.74–2.77 (m, 1H), 2.21–2.38 (m, 2H); ESI-MS
m/z 262, [M+H]+. HRMS (ESI) m/z calcd C14H16FN3ONa [M+Na]+
284.1175, found 284.1173.
4.1.39. (2S,4S)-1-[(2S)-2-Amino-3-(4-nitrophenyl)propanoyl]-4-
fluoropyrrolidine-2-carbonitrile (17e)
4.1.32. tert-Butyl N-[(2S)-1-[(2S,4S)-2-cyano-4-fluoropyrrolidin-
1-yl]-3-(4-fluorophenyl)-1-oxopropan-2-yl]carbamate (16b)
A similar procedure to that described above for 6a gave the de-
sired product 16b. 1H NMR (300 MHz, CDCl3) d 7.19–7.26 (m, 2H),
7.03 (t, J = 6.0 Hz, 2H), 5.20–5.31 (m, 1H), 4.92 (d, J = 9.6 Hz, 1H),
4.42 (q, J = 6.0 Hz, 1H), 3.72 (dd, J1 = 3.9 Hz, J2 = 12.6 Hz, 1H),
2.97–3.80 (m, 3H), 2.56 (t, J = 15.0 Hz, 1H), 2.16–2.32 (m, 1H),
1.42 (s, 9H). ESI-MS m/z 402, [M+H]+.
A similar procedure to that described above for 7a gave the de-
sired product 17e. 1H NMR (300 MHz, DMSO-d6) d 8.19 (d,
J = 8.4 Hz, 2H), 7.53 (d, J = 8.7 Hz, 2H), 5.08–5.26 (m, 1H), 4.31–
4.38 (m, 1H), 3.95 (q, J = 6.0 Hz, 1H), 3.06–3.27 (m, 3H), 2.00–
2.25 (m, 2H); ESI-MS m/z 307, [M+H]+. HRMS (ESI) m/z calcd C14-
H16FN4O3 [M+H]+ 307.1206, found 307.1228.
4.1.40. tert-Butyl N-[(2S)-1-[(2S,4S)-2-cyano-4-fluoropyrrolidin-
1-yl]-3-(4-cyanophenyl)-1-oxopropan-2-yl]carbamate (16f)
A similar procedure to that described above for 6a gave the de-
sired product 16f. 1H NMR (300 MHz, CDCl3) d 7.63 (d, J = 9.0 Hz,
2H), 7.36 (d, J = 6.0 Hz, 2H), 5.12–5.29 (m, 1H), 4.90 (d,
J = 12.0 Hz, 1H), 4.48 (q, J = 9.0 Hz, 1H), 3.73 (dd, J1 = 12.0 Hz,
J2 = 12.0 Hz, 1H), 3.02–3.20 (m, 3H), 2.56 (t, J = 15.0 Hz, 1H),
2.11–2.36 (m, 1H), 1.39 (s, 9H). MS (ESI) m/z 409 [M+Na]+.
4.1.33. (2S,4S)-1-[(2S)-2-Amino-3-(4-fluorophenyl)propanoyl]-
4-fluoropyrrolidine-2-carbonitrile (17b)
A similar procedure to that described above for 7a gave the de-
sired product 17b. 1H NMR (300 MHz, DMSO-d6) d 7.19–7.24 (m,
2H), 6.98–7.05 (m, 2H), 5.25–5.42 (m, 1H), 4.92 (q, J = 6.0 Hz,
1H), 4.40–4.51 (m, 1H), 3.61–3.80 (m, 1H), 2.91–3.11 (m, 2H),
2.56–2.71 (m, 2H), 2.16–2.33 (m, 1H); ESI-MS m/z 279, [M+H]+.
HRMS (ESI) m/z calcd C14H15FN3ONa [M+Na]+ 302.1081, found
302.1083.
4.1.41. (2S,4S)-1-[(2S)-2-Amino-3-(4-cyanophenyl)propanoyl]-
4-fluoropyrrolidine-2-carbonitrile (17f)
4.1.34. tert-Butyl N-[(2S)-1-[(2S,4S)-2-cyano-4-fluoropyrrolidin-
1-yl]-3-(4-methylphenyl)-1-oxopropan-2-yl]carbamate (16c)
A similar procedure to that described above for 6a gave the de-
sired product 16c. 1H NMR (300 MHz, CDCl3) d 7.14 (s, 4H), 5.23–
5.28 (m, 1H), 4.91 (d, J = 9.0 Hz, 1H), 4.38–4.44 (m, 1H), 3.68 (dd,
J1 = 12.0 Hz, J2 = 12.0 Hz, 1H), 2.86–3.01 (m, 3H), 2.54 (t,
J = 15.0 Hz, 1H), 2.31 (s, 3H), 2.11-2.23 (m, 1H), 1.41 (s, 9H). MS
(ESI) m/z 398 [M+Na]+.
A similar procedure to that described above for 7a gave the de-
sired product 17f. 1H NMR (400 MHz, CD3OD) d 7.71 (d, J = 8.0 Hz,
2H), 7.48 (d, J = 8.0 Hz, 2H), 5.17–5.30 (m, 1H), 5.01 (d, J = 8.0 Hz,
1H), 4.35 (q, J = 6.0 Hz, 1H), 3.56–3.69 (m, 1H), 3.20–3.30 (m,
2H), 2.98–3.07 (m, 1H), 2.53 (t, J = 12.0 Hz, 1H), 2.24–2.43 (m,
1H). ESI-LRMS: 287 [M+H]+. ESI-HRMS calcd for C15H16N4OF m/z
287.1308 [M+H]+, found 287.1324 [M+H]+.
4.1.42. tert-Butyl N-[(2S)-1-[(2S,4S)-2-cyano-4-fluoropyrrolidin-
1-yl]-3-[4-(trifluoromethyl)phenyl]-1-oxopropan-2-
yl]carbamate (16g)
4.1.35. (2S,4S)-1-[(2S)-2-Amino-3-(4-methylphenyl)propanoyl] -
4-fluoropyrrolidine-2-carbonitrile (17c)
A similar procedure to that described above for 7a gave the
desired product 17c. 1H NMR (400 MHz, CD3OD) d 7.17 (s, 4H),
5.11–5.25(m, 1H), 5.01 (d, J = 12.0 Hz, 1H), 4.20–4.24 (m, 1H),
3.51–3.65 (m, 1H), 3.07–3.18 (m, 2H), 2.76–2.85 (m, 1H), 2.48
(t, J = 15.0 Hz, 1H), 2.23–2.44 (m, 4H). ESI-LRMS: 276[M+H]. ESI-
HRMS calcd for C15H18N3OFNa m/z 298.1332 [M+Na]+, found
298.1332[M+Na]+
A similar procedure to that described above for 6a gave the de-
sired product 16g. 1H NMR (300 MHz, CDCl3) d 7.63 (d, J = 6.0 Hz,
2H), 7.38 (d, J = 9.0 Hz, 2H), 5.23–5.27 (m, 1H), 4.91 (d, J = 9.0 Hz,
1H), 4.48 (q, J = 6.0 Hz, 1H), 3.70 (dd, J1 = 12.0 Hz, J2 = 12.0 Hz,
1H), 3.06–3.12 (m, 3H), 2.56 (t, J = 15.0 Hz, 1H), 2.11–2.34 (m,
1H), 1.41 (s, 9H). MS (ESI) m/z 452 [M+Na]+.
4.1.43. (2S,4S)-1-[(2S)-2-Amino-3-[4-(trifluoromethyl)phenyl]
propanoyl]-4-fluoropyrrolidine-2-carbonitrile (17g)
4.1.36. tert-Butyl N-[(2S)-1-[(2S,4S)-2-cyano-4-fluoropyrrolidin-
1-yl]-3-(4-methoxyphenyl)-1-oxopropan-2-yl]carbamate (16d)
A similar procedure to that described above for 6a gave the de-
sired product 16d. 1H NMR (300 MHz, CDCl3) d 8.12–8.21 (m, 2H),
8.02 (s, 1H), 7.37–7.49 (m, 2H), 5.25–5.31 (m, 1H), 4.56–4.78 (m,
1H), 4.05–4.14 (m, 1H), 3.73–3.85 (m, 1H), 3.29 (dd, J1 = 5.1 Hz,
J2 = 5.1 Hz, 1H), 3.04–3.20 (m, 1H), 2.87–2.98 (m, 1H), 2.57–2.73
(m, 2H). ESI-MS m/z 414, [M+Na]+.
A similar procedure to that described above for 7a gave the
desired product 17g. 1H NMR (400 MHz, CD3OD)
d 7.65
(d, J = 8.0 Hz, 2H), 7.49 (d, J = 8.0 Hz, 2H), 5.13–5.28 (m, 1H),
5.01 (d, J = 8.0 Hz, 1H), 4.35 (q, J = 6.0 Hz, 1H), 3.54–3.68 (m,
1H), 3.21–3.33 (m, 2H), 2.95 (q, J = 6.0 Hz, 1H), 2.50 (t,
J = 12.0 Hz, 1H), 2.24–2.41 (m, 1H). ESI-LRMS: 330 [M+H]+. ESI-
HRMS calcd for
C
15H16N3OF4 m/z 330.1230 [M+H]+, found
330.1233 [M+H]+.
4.1.37. (2S,4S)-1-[(2S)-2-Amino-3-(4-methoxyphenyl)
propanoyl]-4-fluoropyrrolidine-2-carbonitrile (17d)
A similar procedure to that described above for 7a gave the
desired product 17d. 1H NMR (300 MHz, DMSO-d6) d 8.32 (s,
1H), 7.47 (d, J = 8.1 Hz, 2H), 7.12 (d, J = 7.8 Hz, 2H), 4.41–4.80
(m, 4H), 4.19–4.24 (m, 1H), 3.62–3.78 (m, 1H), 2.82–3.18 (m,
2H), 2.38–2.43 (m, 1H), 2.30 (s, 3H); ESI-MS m/z 292, [M+H]+.
HRMS (ESI) m/z calcd C15H18FN3O2 [M+H]+ 292.1461., found
292.1456.
4.1.44. tert-Butyl N-[(2S)-1-[(2S,4S)-2-cyano-4-fluoropyrrolidin-
1-yl]-3-(4-tert-butylphenyl)-1-oxopropan-2-yl]carbamate (16h)
A similar procedure to that described above for 6a gave the de-
sired product 16h. 1H NMR (300 MHz, CDCl3) d 7.36 (d, J = 6.0 Hz,
2H), 7.18 (d, J = 6.0 Hz, 2H), 5.18–5.29 (m, 1H), 4.92 (d, J = 9.0 Hz,
1H), 4.35–4.42 (m, 1H), 3.60 (dd, J1 = 12.0 Hz, J2 = 12.0 Hz, 1H),
2.72–3.04 (m, 3H), 2.49 (t, J = 15.0 Hz, 1H), 2.04–2.29 (m, 1H),
1.41 (s, 9H), 1.28 (s, 9H). MS (ESI) m/z 440 [M+Na]+.