J.-D. Malcor et al. / Tetrahedron 70 (2014) 4631e4639
4637
solid. Yield: 95%. Mp 64.5e67.5 ꢀC. 1H NMR (400 MHz, DMSO-d6)
111.9, 110.5, 100.6, 55.0, 24.8. HRMS (ESI) m/z: calcd for C16H15N4O2
[MþH]þ 295.1195, found [MþH]þ¼295.1197.
d
(ppm) 11.61 (s, 1H), 9.60 (s, 1H), 7.41 (d, 1H, J¼7.0 Hz), 6.91 (t, 1H,
J¼3.0 Hz), 6.80 (t, 1H, J¼2.5 Hz), 4.30 (q, 2H, J¼6.0 Hz), 3.89 (t, 1H,
J¼6.3 Hz), 1.89 (m, 1H), 1.40 (s, 9H), 1.33 (t, 3H, J¼7.1 Hz), 1.24 (m,
2H), 0.87 (d, 3H, J¼6.8 Hz), 0.82 (t, 3H, J¼7.3 Hz). 13C NMR
4.3.10. Ethyl 3-(2-((tert-butoxycarbonyl)amino)hexanamido)-1H-pyr-
role-2-carboxylate (32d). Colorless oil. Yield: 93%.1H NMR (400 MHz,
(75 MHz, DMSO-d6)
d
(ppm) 169.7, 161.2, 156.4, 131.2, 123.7, 108.3,
DMSO-d6)
d
(ppm) 11.59 (s, 1H), 9.69 (s, 1H), 7.47 (d, 1H, J¼6.8 Hz),
102.3, 78.9, 60.6, 60.1, 36.3, 28.6, 24.9, 16.1, 14.9, 11.9. HRMS (ESI)
6.91 (t,1H, J¼2.9 Hz), 6.80 (t,1H, J¼2.5 Hz), 4.30 (m, 2H), 4.29 (m,1H),
1.79 (m, 1H), 1.58 (m, 1H), 1.41 (t, 9H), 1.33 (t, 3H, J¼7.1 Hz), 1.28 (m,
2H),1.20 (m, 2H), 0.86 (t, 3H, J¼6.8 Hz). 13C NMR (75 MHz, DMSO-d6)
m/z: calcd for
C
18H30N3O5 [MþH]þ 368.2185, found
[MþH]þ¼368.2181.
d
(ppm) 170.6, 161.2, 156.3, 131.3, 123.8, 108.4, 102.2, 79.0, 60.1, 55.9,
4.3.5. 3-(2-((tert-Butoxycarbonyl)amino)-3-methylpentanamido)-
31.0, 28.7, 28.6, 15.0, 14.4, 14.3. HRMS (ESI) m/z: calcd for C18H30N3O5
[MþH]þ 368.2185, found [MþH]þ¼368.2180.
1H-pyrrole-2-carboxylic acid (33b). Colorless solid. Yield: 96%. Mp
144.4e148 ꢀC. 1H NMR (400 MHz, DMSO-d6)
d (ppm) 12.71, 11.51 (s,
1H), 9.72 (s, 1H), 7.39 (d, 1H, J¼7.3 Hz), 6.84 (t, 1H, J¼2.9 Hz), 6.78 (t,
1H, J¼2.5 Hz), 3.86 (t, 1H, J¼6.4 Hz), 1.90 (m, 1H), 1.40 (s, 9H), 1.36
(m, 1H), 1.26 (m, 1H), 0.86 (d, 3H, J¼6.9 Hz), 0.81 (t, 3H, J¼7.2 Hz).
4.3.11. 3-(2-((tert-Butoxycarbonyl)amino)hexanamido)-1H-pyrrole-
2-carboxylic acid (33d). Colorless solid. Yield: 50%. Mp
93.5e91.1 ꢀC. 1H NMR (400 MHz, DMSO-d6)
d (ppm) 11.44 (s, 1H),
13C NMR (75 MHz, DMSO-d6)
d
(ppm) 167.7, 161.0, 154.4, 129.1,
9.82 (s, 1H), 7.46 (d, 1H, J¼7.0 Hz), 6.91 (t, 1H, J¼2.9 Hz), 6.80 (t, 1H,
120.8, 107.0, 100.2, 76.9, 58.5, 34.4, 26.6, 22.9, 14.1, 10.1. HRMS (ESI)
J¼2.4 Hz), 3.89 (m, 1H), 1.79 (m, 1H). 1.576 (m, 1H), 1.41 (t, 9H), 1.29
m/z: calcd for
C
11H18N3O3 [MþH]þ 240.1348, found
(m, 4H), 0.86 (t, 3H, J¼6.8 Hz). 13C NMR (75 MHz, DMSO-d6)
d (ppm)
[MþH]þ¼240.1332 (unprotected).
170.0, 162.6, 155.7, 130.5, 122.3, 108.7, 101.5, 78.4, 55.3, 30.5, 28.1,
27.9, 21.7, 13.8. HRMS (ESI) m/z: calcd for C11H18N3O3 [MþH]þ
240.1348, found [MþH]þ¼240.1348 (unprotected).
4.3.6. 3-(Sec-butyl)-3,4-dihydropyrrolo[3,2-e][1,4]diazepine-
2,5(1H,6H)-dione (35b). Colorless solid. Yield: 78%. Mp
139.8e141.3 ꢀC. 1H NMR (400 MHz, DMSO-d6)
d
(ppm) 11.37 (s, 1H),
4.3.12. 3-Butyl-3,4-dihydropyrrolo[3,2-e][1,4]diazepine-2,5(1H,6H)-
dione (35d). Brown oil. The crude product was purified by silica gel
flash chromatography using 0% MeOH to 7% MeOH in CH2Cl2 to
yield a colorless solid. Yield: 59%. Mp 130.1e131.9 ꢀC. 1H NMR
10.18 (s, 1H), 7.71 (d, 1H, J¼6.6 Hz), 6.86 (t, 1H, J¼2.9 Hz), 5.79 (t, 1H,
J¼2.6 Hz), 3.28 (d, 1H, J¼3.6 Hz, 6.7 Hz), 1.82 (m, 1H), 1.54 (m, 1H),
1.17 (m, 1H), 0.86 (d, 3H, J¼6.7 Hz), 0.78 (t, 3H, J¼7.4 Hz). 13C NMR
(75 MHz, DMSO-d6)
d
(ppm) 169.3, 162.6, 127.6, 122.9, 115.6, 100.4,
(400 MHz, DMSO-d6) d (ppm) 11.38 (s, 1H), 10.16 (s, 1H), 7.54 (d, 1H,
61.0, 32.5, 24.9, 16.3, 10.5. HRMS (ESI) m/z: calcd for C11H16N3O2
J¼4.8 Hz), 6.86 (t, 1H, J¼2.9 Hz), 5.81 (t, 1H, J¼2.6 Hz), 3.56 (s, 1H),
[MþH]þ 222.1243, found [MþH]þ¼222.1252.
1.78 (m, 1H), 1.58 (m, 1H), 1.27 (m, 4H), 0.85 (t, 3H, J¼7.2 Hz). 13
C
NMR (75 MHz, DMSO-d6)
d (ppm) 169.2, 162.3, 127.5, 122.6, 115.2,
4.3.7. Ethyl
3-(2-((tert-butoxycarbonyl)amino)-3-(1H-indol-3-yl)
100.1, 53.9, 28.2, 27.9, 21.9, 13.9. HRMS (ESI) m/z: calcd for
C
propanamido)-1H-pyrrole-2-carboxylate (32c). Colorless solid.
11H16N3O2 [MþH]þ 222.1243, found [MþH]þ¼222.1246.
Yield: 94%. Mp 103.4e105.8 ꢀC. 1H NMR (400 MHz, DMSO-d6)
d
(ppm) 11.64 (s,1H),10.83 (s,1H), 9.78 (s,1H), 7.57 (d,1H, J¼7.8 Hz),
4.3.13. Ethyl 3-(2-(1-(tert-butoxy)-4-methylpentanamido)-1H-pyr-
7.47 (d, 1H, J¼7.5 Hz), 7.34 (d, 1H, J¼8.0 Hz), 7.16 (s, 1H), 7.07 (t, 1H,
J¼7.0 Hz), 6.98 (t, 1H, J¼7.9 Hz), 6.94 (t, 1H, J¼2.9 Hz), 6.86 (t, 1H,
J¼2.5 Hz), 4.28 (q, 2H, J¼6.9 Hz), 4.23 (m, 1H), 3.29 (dd, 1H,
J¼3.6 Hz, 11.2 Hz), 2.99 (dd, 1H, J¼10.4 Hz, 14.6 Hz), 1.32 (s, 1H), 1.06
role-2-carboxylate (32e). Colorless solid. Yield: 98%. Mp
55.7e57.4 ꢀC. 1H NMR (400 MHz, DMSO-d6)
d (ppm) 9.68 (s, 1H),
7.45 (d, 1H, J¼6.6 Hz), 6.87 (t, 1H, J¼2.9 Hz), 6.77 (t, 1H, J¼2.5 Hz),
4.27 (q, 2H, J¼7.1 Hz), 3.94 (m, 1H), 1.55 (m, 3H), 1.41 (d, 9H), 1.29 (t,
3H, J¼7.1 Hz), 0.87 (d, 3H, J¼6.4 Hz), 0.84 (d, 3H, J¼6.3 Hz). 13C NMR
(t, 3H, J¼7.0 Hz). 13C NMR (75 MHz, DMSO-d6)
d (ppm) 170.3, 161.2,
156.0, 136.6, 131.3, 127.6, 123.9, 123.8, 121.4, 118.8, 118.6, 111.8, 111.0,
108.4, 102.3, 79.0, 60.1, 56.9, 28.5, 27.3, 14.9. HRMS (ESI) m/z: calcd
for C23H29N4O5 [MþH]þ 441.2138, found [MþH]þ¼441.2126.
(75 MHz, DMSO-d6) d (ppm) 170.8, 161.1, 156.1, 131.8, 123.7, 108.3,
102.13, 79.0, 60.0, 54.2, 28.5, 24.9, 23.4, 21.6, 14.9. HRMS (ESI) m/z:
calcd for C18H30N3O5 [MþH]þ 368.2185, found [MþH]þ¼368.2189.
4.3.8. 3-(2-((tert-Butoxycarbonyl)amino)-3-(1H-indol-3-yl)prop-
4.3.14. 3-(2-(1-(tert-Butoxy)-4-methylpentanamido)-1H-pyrrole-2-
anamido)-1H-pyrrole-2-carboxylic acid (33c). Colorless solid. Yield:
carboxylic acid (33e). Colorless solid. Yield: 76%. Mp 76.5e78.9 ꢀC.
93%. Mp 116.6e118.5 ꢀC. 1H NMR (400 MHz, DMSO-d6)
d
(ppm)
1H NMR (400 MHz, DMSO-d6)
d (ppm) 11.48 (s, 1H), 9.85 (d, 1H,
12.68 (s, 1H), 11.51 (s, 1H), 10.82 (s, 1H), 9.92 (s, 1H), 7.57 (d, 1H,
J¼7.8 Hz), 7.51 (dd, 1H, J¼7.5 Hz, 13.1 Hz), 7.35 (d, 1H, J¼8.0 Hz), 7.17
(s, 1H), 7.07 (t, 1H, J¼6.9 Hz), 6.99 (t, 1H, J¼6.9 Hz), 6.89 (t, 1H,
J¼2.9 Hz), 6.86 (t, 1H, J¼2.5 Hz), 4.19 (m, 1H), 3.14 (dd, 1H, J¼4.6 Hz,
14.5 Hz), 2.97 (dd, 1H, J¼11.1 Hz, 14.5 Hz), 1.328 (s, 1H). 13C NMR
J¼7.4 Hz), 7.52 (d, 1H, J¼8.2 Hz), 7.06 (s, 1H), 6.86 (t, 1H, J¼2.9 Hz),
6.80 (t,1H, J¼2.5 Hz), 3.93 (m, 1H), 1.62 (m, 3H), 1.41 (d, 9H), 0.89 (d,
3H, J¼6.5 Hz), 0.86 (d, 3H, J¼6.4 Hz). 13C NMR (75 MHz, DMSO-d6)
d
(ppm) 170.8, 163.0, 156.1, 131.1, 122.9, 109.0, 102.0, 78.4, 52.3, 28.7,
24.8, 23.4, 21.7. HRMS (ESI) m/z: calcd for C11H18N3O3 [MþH]þ
(75 MHz, DMSO-d6)
d (ppm) 170.2, 162.9, 156.0, 136.6, 131.1, 127.6,
240.1348, found [MþH]þ¼240.1342 (unprotected).
123.9, 122.9, 121.4, 118.8, 118.6, 111.8, 111.2, 109.0, 102.8, 78.9, 56.8,
28.5, 27.2. HRMS (ESI) m/z: calcd for C16H17N4O3 [MþH]þ 313.1301,
found [MþH]þ¼313.1315 (unprotected).
4.3.15. 3-Isobutyl-3,4-dihydropyrrolo[3,2-e][1,4]diazepine-
2,5(1H,6H)-dione (35e). Colorless solid. Yield: 47%. Mp
147.8e150.2 ꢀC. 1H NMR (400 MHz, DMSO-d6)
d (ppm) 11.40 (s, 1H),
4.3.9. 3-((1H-Indol-3-yl)methyl)-3,4-dihydropyrrolo[3,2-e][1,4]dia-
10.20 (d, 1H, J¼7.4 Hz), 7.56 (d, 1H, J¼4.9 Hz), 6.90 (t, 1H, J¼2.9 Hz),
5.82 (t, 1H, J¼2.5 Hz), 3.61 (m, 1H), 1.62 (m, 3H), 0.88 (d, 3H,
J¼6.5 Hz), 0.83 (d, 3H, J¼6.4 Hz). 13C NMR (75 MHz, DMSO-d6)
zepine-2,5(1H,6H)-dione (35c). Colorless solid. Yield: 74%. Mp
187.8e191.2 ꢀC. 1H NMR (400 MHz, DMSO-d6)
d (ppm) 11.37 (s, 1H),
10.86 (s, 1H), 10.25 (s, 1H), 7.45 (d, 1H, J¼7.9 Hz), 7.42 (dd, 1H,
J¼4.8 Hz, 13.1 Hz), 7.34 (d, 1H, J¼8.0 Hz), 7.23 (d, 1H, J¼2.2 Hz), 7.06
(t, 1H, J¼7.9 Hz), 6.93 (t, 1H, J¼7.1 Hz), 6.89 (t, 1H, J¼2.9 Hz), 5.82 (t,
1H, J¼2.6 Hz), 3.88 (m, 1H), 3.29 (dd, 1H, J¼5.8 Hz, 14.9 Hz), 2.99
d (ppm) 169.6, 162.6, 127.6, 123.0, 115.6, 100.5, 52.6, 37.6, 24.5, 23.1,
22.2. HRMS (ESI) m/z: calcd for C11H16N3O2 [MþH]þ 222.1243,
found [MþH]þ¼222.1239.
(dd, 1H, J¼8.9 Hz, 14.8 Hz). 13C NMR (75 MHz, DMSO-d6)
d
(ppm)
4.3.16. Ethyl 3-(2-((tert-butoxycarbonyl)amino)-4-(methylthio)bu-
tanamido)-1H-pyrrole-2-carboxylate (32f). Colorless oil. Yield: 88%.
169.5, 162.5, 136.6, 128.0, 127.5, 124.7, 123.1, 121.4, 118.8, 118.6, 115.6,