Katritzky et al.
1.57 (d, J ) 6.9 Hz, 3H), 5.28 (quintet, J ) 6.9 Hz, 1H), 6.38
(quintet, J ) 1.8 Hz, 1H), 7.07 (s, 1H), 7.16 (s, 1H), 7.58 (br s,
1H), 9.80 (br s, 1H); 13C NMR (CDCl3) δ 20.6, 50.8, 112.0, 115.9
(q, J ) 285.2 Hz), 118.5, 127.0, 128.4, 156.7 (q, J ) 37.6 Hz),
186.5. Anal. Calcd for C9H9F3N2O2: C, 46.16; H, 3.87; N, 11.96.
Found: C, 46.39; H, 3.77; N, 11.80.
5.31(q, J ) 6.3 Hz, 1H), 5.68 (d, J ) 8.4 Hz, 1H), 6.15 (q, J )
2.7 Hz, 1H), 6.87 (s, 1H), 7.03-7.05 (m, 3H), 7.21-7.23 (m,
3H), 7.30 (t, J ) 7.5 Hz, 2H), 7.40 (t, J ) 7.2 Hz, 2H), 7.57 (t,
J ) 6.6 Hz, 2H), 7.76 (d, J ) 7.2 Hz, 2H); 13C NMR (DMSO-
d6) δ 37.7, 40.5, 47.2, 56.7, 66.9, 108.8, 120.0, 120.5, 125.2,
125.3, 126.9, 127.1, 127.7, 128.3, 129.5, 132.3, 136.3, 141.3,
144.0, 155.6, 187.5. Anal. Calcd for C29H26N2O3: C, 77.31; H,
5.82; N, 6.22. Found: C, 76.93; H, 5.76; N, 6.21.
9H-Fluoren-9-ylmethyl-N-[(1S)-1-(1H-indol-3-ylmethyl)-
2-oxo-2-(1-methyl-1H-pyrrol-2-yl)ethyl]carbamate (3d):
gray microcrystals; yield, 45%; mp 154-155 °C; [R]23D ) +35.6
(c 1.6, DMF); 1H NMR (DMSO-d6) δ 3.28 (dd, J ) 14.1, 5.1
Hz, 1H), 3.41 (dd, J ) 14.7, 6.6 Hz, 1H), 3.56 (s, 3H), 4.20 (t,
J ) 7.2 Hz, 1H), 4.29-4.42 (m, 2H), 5.25 (q, J ) 6.3 Hz, 1H),
5.84 (d, J ) 8.1 Hz, 1H), 6.54 (d, J ) 2.1 Hz, 1H), 6.60 (s, 1H),
6.86 (d, J ) 1.8 Hz, 1H), 7.05-7.10 (m, 2H), 7.15 (t, J ) 7.5
Hz, 1H), 7.29 (t, J ) 7.8 Hz, 3H), 7.39 (t, J ) 7.5 Hz, 2H), 7.56
(t, J ) 7.5 Hz, 3H), 7.75 (d, J ) 7.5 Hz, 2H), 8.00 (s, 1H); 13C
NMR (DMSO-d6) δ 30.1, 36.8, 47.4, 57.0, 67.1, 109.9, 111.2,
119.1, 119.8, 120.1 (2C), 122.2, 123.1, 123.9, 125.4, 125.5,
127.3, 127.8 (2C), 128.0, 136.2, 141.5, 144.2, 156.1, 193.0;
HRMS calcd for C31H27N3O3 (M + H)+ 490.2125, found
490.2151.
9H-Fluoren-9-ylmethyl N-[(1S)-1-benzyl-2-oxo-2-(1H-
pyrrol-2-yl)ethyl]carbamate (2c): colorless needles; yield,
1
72%; mp 186-187 °C; [R]23 ) +16.7 (c 1.6, DMF); H NMR
D
(DMSO-d6) δ 3.09 (dd, J ) 13.8, 6.0 Hz, 1H), 3.26 (dd, J )
13.5, 6.0 Hz, 1H), 4.19 (t, J ) 6.9 Hz, 1H), 4.29 (t, J ) 6.9 Hz,
1H), 4.44 (dd, J ) 10.2, 7.2 Hz, 1H), 5.29 (dd, J ) 14.1, 6.6
Hz, 1H), 5.69 (d, J ) 8.4 Hz, 1H), 6.29 (d, J ) 3.3 Hz, 1H),
6.99 (s, 1H), 7.05 (d, J ) 2.4 Hz, 2H), 7.20 (d, J ) 6.3 Hz, 3H),
7.29 (t, J ) 7.5 Hz, 2H), 7.39 (t, J ) 7.2 Hz, 2H), 7.56 (t, J )
4.5 Hz, 2H), 7.76 (d, J ) 7.5 Hz, 2H), 9.60 (br s, 1H); 13C NMR
(DMSO-d6) δ 40.4., 47.4, 56.6, 67.1, 111.6, 118.0, 120.2, 125.4,
126.1, 127.1, 127.2, 127.9, 128.6, 129.7, 136.2, 141.5, 144.0,
144.1, 155.8, 187.2. Anal. Calcd for C28H24N2O3: C, 77.04; H,
5.54; N, 6.42. Found: C, 76.79; H, 5.70; N, 6.29.
9H-Fluoren-9-ylmethyl-N-[(1S)-1-(1H-indol-3-ylmethyl)-
2-oxo-2-(1H-pyrrol-2-yl)ethyl] carbamate (2d): white plates;
1
yield, 52%; mp 196-197 °C; [R]23 ) +32.5 (c 1.6, DMF); H
D
NMR (DMSO-d6) δ 3.04 (dd, J ) 14.7, 9.3 Hz, 1H), 3.22 (dd, J
) 14.7, 5.1 Hz, 1H), 4.18-4.21 (m, 3H), 4.97-5.04 (m, 1H),
6.21-6.23 (m, 1H), 6.99 (t, J ) 7.2 Hz, 1H), 7.04-7.09 (m, 2H),
7.13 (s, 1H), 7.19 (d, J ) 2.1 Hz, 1H), 7.25-7.43 (m, 5H), 7.57
(d, J ) 7.8 Hz, 1H), 7.67 (d, J ) 6.6 Hz, 2H), 7.87 (d, J ) 7.5
Hz, 2H), 7.92 (s, 1H), 10.85 (s, 1H), 11.90 (s, 1H); 13C NMR
(DMSO-d6) δ 27.7, 46.6, 56.4, 65.7, 110.0, 110.2, 111.4, 116.8,
118.1, 118.4, 120.1, 120.9, 123.8, 125.3, 126.1, 127.0, 127.2,
127.6, 129.9, 136.1, 140.7, 143.8, 155.7, 188.2. Anal. Calcd for
C30H25N3O3: C, 75.77; H, 5.30; N, 8.84. Found: C, 75.55; H,
5.18; N, 8.76.
9H-Fluoren-9-ylmethyl N-[(1S)-3-(methylsulfanyl)-1-
(1H-pyrrol-2-ylcarbonyl) propyl]carbamate (2e): colorless
plates; yield, 66%; mp 163-164 °C; [R]23D ) -5.9 (c 1.6, DMF);
1H NMR (DMSO-d6) δ 1.92-2.01 (m, 1H), 2.06 (s, 3H), 2.14-
2.26 (m, 1H), 2.51-2.60 (m, 2H), 4.21 (t, J ) 6.9 Hz, 1H), 4.35-
4.56 (m, 2H), 5.21 (dd, J ) 9.3, 8.1 Hz, 1H), 5.83 (d, J ) 8.4
Hz, 1H), 6.32 (d, J ) 3.3 Hz, 1H), 7.08 (s, 1H), 7.12 (s, 1H),
7.28 (t, J ) 7.2 Hz, 2H), 7.38 (t, J ) 7.8 Hz, 2H), 7.59 (d, J )
7.2 Hz, 2H), 7.75 (d, J ) 7.8 Hz, 2H), 9.80 (br s, 1H); 13C NMR
(DMSO-d6) δ 15.6, 30.2, 34.2, 47.2, 54.6, 67.0, 111.5, 118.2,
120.0, 125.1, 126.3, 127.1, 127.7, 129.4, 141.3, 143.9, 156.1,
187.7. Anal. Calcd for C24H24N2O3S: C, 68.55; H, 5.75; N, 6.66.
Found: C, 68.26; H, 5.85; N, 6.74.
N-[(1S)-1-Benzyl-2-(1-methyl-1H-pyrrol-2-yl)-2-oxoethyl]-
2,2,2-trifluoroacetamide (3a): colorless needles; yield, 78%;
mp 109-110 °C; [R]23D ) +43.6 (c 1.6, CHCl3); 1H NMR (CDCl3)
δ 3.17 (dd, J ) 13.8, 4.8 Hz, 1H), 3.31 (dd, J ) 13.8, 6.6 Hz,
1H), 3.68 (s, 3H), 5.32 (dd, J ) 12.6, 6.0 Hz, 1H), 6.62 (d, J )
1.5 Hz, 2H), 7.00-7.03 (m, 2H), 7.19-7.26 (m, 4H), 7.36 (br s,
1H); 13C NMR (CDCl3) δ 36.8, 39.3, 56.4, 109.9, 115.9 (q, J )
287.3 Hz), 122.3, 124.3, 127.3, 128.3, 128.5, 129.7, 135.4, 156.5
(q, J ) 37.2 Hz), 190.1. Anal. Calcd for C16H15F3N2O2: C, 59.26;
H, 4.66; N, 8.64. Found: C, 59.17; H, 4.62; N, 8.47.
9H-Fluoren-9-ylmethyl N-[(1S)-1-[(1-methyl-1H-pyrrol-
2-yl)carbonyl]-3-(methylsulfanyl)propyl]carbamate (3e):
light yellow needles; yield, 60%; mp 109-110 °C; [R]23D ) -17.3
1
(c 1.6, DMF); H NMR (DMSO-d6) δ 1.86-2.00 (m, 1H), 2.06
(s, 3H), 2.14-2.25 (m, 1H), 2.44-2.63 (m, 2H), 3.66 (s, 3H),
4.21 (t, J ) 6.3 Hz, 1H), 4.37 (d, J ) 6.9 Hz, 2H), 5.07-5.13
(m, 1H), 5.84 (d, J ) 8.4 Hz, 1H), 6.59 (t, J ) 2.4 Hz, 1H),
6.65 (s, 1H), 7.26-7.32 (m, 2H), 7.38 (t, J ) 6.0 Hz, 3H), 7.60
(d, J ) 7.2 Hz, 2H), 7.75 (d, J ) 7.5 Hz, 2H); 13C NMR (DMSO-
d6) δ 15.7, 30.3, 34.2, 36.9, 47.3, 55.6, 67.0, 110.0, 120.1, 122.8,
124.1, 125.3, 127.2, 127.8, 128.0, 141.4, 143.9, 156.2, 192.7.
Anal. Calcd for C25H26N2O3S: C, 69.10; H, 6.03; N, 6.45.
Found: C, 69.11; H, 5.98; N, 6.46.
9H-Fluoren-9-ylmethyl N-[(1S)-4-oxo-4-(1H-pyrrol-2-
yl)-1-(1H-pyrrol-2-ylcarbonyl)butyl]carbamate (4): light
violet microcrystals; yield, 35%; mp 140-141 °C; [R]23D ) +12.2
(c 1.6, DMF); 1H NMR (DMSO-d6) δ 1.80-1.92 (m, 1H), 2.09-
2.20 (m, 1H), 2.80-3.03 (m, 2H), 4.22-4.27 (m, 3H), 4.83
(quintet, J ) 7.5 Hz, 1H), 6.20 (d, J ) 17.1 Hz, 2H), 6.94 (s,
1H), 7.10 (d, J ) 16.8 Hz, 2H), 7.29 (s, 1H), 7.34 (t, J ) 7.5
Hz, 2H), 7.41 (t, J ) 7.2 Hz, 2H), 7.73 (t, J ) 6.9 Hz, 2H), 7.82
(d, J ) 8.1 Hz, 1H), 7.89 (d, J ) 7.5 Hz, 2H), 11.86 (d, J ) 9.6
Hz, 2H); 13C NMR (DMSO-d6) δ 27.2, 33.8, 46.6, 55.4, 65.6,
109.7, 109.9, 116.3, 116.9, 120.1, 125.3, 125.9, 127.1, 127.6,
129.6, 131.5, 140.7, 143.7, 143.9, 156.1, 188.4, 188.8. Anal.
Calcd for C28H25N3O4: C, 71.93; H, 5.39; N, 8.99. Found: C,
72.11; H, 5.41; N, 8.91.
N-[(1S)-1-Benzyl-2-(1H-indol-3-yl)-2-oxoethyl]-2,2,2-tri-
fluoroacetamide (5a): gray needles; yield, 85%; mp 198-
199 °C; [R]23D ) +22.0 (c 1.6, CHCl3); 1H NMR (CDCl3) δ 3.22
(dd, J ) 13.5, 5.1 Hz, 1H), 3.31 (dd, J ) 13.5, 6.3 Hz, 1H),
5.47 (dd, J ) 12.9, 7.2 Hz, 1H), 7.05 (t, J ) 3.6 Hz, 2H), 7.20-
7.22 (m, 3H), 7.33-7.44 (m, 3H), 7.55 (d, J ) 7.2 Hz, 1H), 7.64
(d, J ) 3.0 Hz, 1H), 8.33-8.35 (m, 1H), 8.83 (br s, 1H); 13C
NMR (CDCl3) δ 39.8, 56.4, 111.7, 115.2, 115.7 (q, J ) 285.8
Hz), 122.2, 123.5, 124.5, 125.3, 127.3, 128.5, 129.5, 132.5,
135.2, 136.2, 156.6 (q, J ) 37.0 Hz), 190.1. Anal. Calcd for
C13H11F3N2O2: C, 63.33; H, 4.20; N, 7.77. Found: C, 62.98; H,
4.08; N, 7.75.
2,2,2-Trifluoro-N-[(1S)-1-methyl-2-(1-methyl-1H-pyrrol-
2-yl)-2-oxoethyl]-acetamide (3b): colorless needles; yield,
1
75%; mp 120-121 °C; [R]23 ) -7.4 (c 1.6, CHCl3); H NMR
D
(CDCl3) δ 1.53 (d, J ) 7.2 Hz, 3H), 3.73 (s, 3H), 5.13 (quintet,
J ) 6.3 Hz, 1H), 6.61-6.60 (m, 2H), 7.40 (t, J ) 1.8 Hz, 1H),
7.73 (br s, 1H); 13C NMR (CDCl3) δ 19.9, 36.7, 51.4, 109.7, 115.7
(q, J ) 286.4 Hz), 121.2, 124.1, 127.8, 156.2 (q, J ) 37.0 Hz),
191.3. Anal. Calcd for C10H11F3N2O2: C, 48.39; H, 4.47; N,
11.29. Found: C, 48.70; H, 4.38; N, 11.15.
2,2,2-Trifluoro-N-[(1S)-2-(1H-indol-3-yl)-1-methyl-2-oxo-
ethyl]acetamide (5b): colorless microcrystals; yield, 79%; mp
1
189-190 °C; [R]23 ) -7.0 (c 1.6, CHCl3); H NMR (CDCl3) δ
D
1.61 (d, J ) 6.9 Hz, 3H), 5.31 (quintet, J ) 6.9 Hz, 1H), 7.23
(br s, 1H), 7.33-7.45 (m, 2H), 7.44-7.48 (m, 1H), 7.97 (d, J )
3.3 Hz, 1H), 8.35 (t, J ) 5.4 Hz, 1H), 8.89 (br s, 1H); 13C NMR
(CDCl3) δ 20.4, 51.5, 111.7, 114.2, 115.7 (q, J ) 286.4 Hz),
122.3, 123.5, 124.5, 125.5, 132.0, 136.4, 156.5 (q, J ) 37.6 Hz),
191.5. Anal. Calcd for C13H11F3N2O2: C, 54.93; H, 3.90; N, 9.86.
Found: C, 54.98; H, 3.91; N, 9.85.
9H-Fluoren-9-ylmethyl N-[(1S)-1-benzyl-2-(1-methyl-
1H-pyrrol-2-yl)-2-oxoethyl]carbamate (3c): colorless needles;
yield, 56%; mp 172-173 °C; [R]23 ) +9.9 (c 1.6, DMF); 1H
D
NMR (DMSO-d6) δ 3.05 (dd, J ) 13.8, 6.3 Hz, 1H), 3.25 (dd, J
) 13.8, 5.7 Hz, 1H), 3.89 (s, 3H), 4.20 (t, J ) 7.2 Hz, 1H), 4.29
(dd, J ) 10.5, 7.5 Hz, 1H), 4.43 (dd, J ) 10.2, 7.2 Hz, 1H),
4998 J. Org. Chem., Vol. 70, No. 13, 2005