M. Noguchi et al. / Tetrahedron 59 (2003) 4581–4590
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4.4.2. Methyl 3-anilino-1-benzyl-2-isopropyl-4-oxo-
1,2,3,4-tetrahydropyrido[1,2-a]pyrrolo[2,3-d]pyrimi-
dine-2-carboxylate (6c). Colorless prisms from benzene–
hexane; mp 111–1138C; IR (KBr): 3300 (NH), 1735, 1690
(CO); 1H NMR (CDCl3): 0.89, 1.00 (each 3H, each d,
J¼6.9 Hz, CHMe2), 2.76 (1H, m, CHMe2), 3.32 (3H, s,
OMe), 4.06 (1H, d, J¼9.2 Hz, NHPh, exchanged with D2O),
4.61, 4.78 (each 1H, each d, J¼15.8 Hz, CH2Ph), 5.28 (1H,
d, J¼9.2 Hz, 3-H), 6.71–7.44 (11H, ov, Ph–H and 9-H),
6.95 (1H, dt, J¼1.3, 6.9 Hz, 7-H), 7.64 (1H, ddd, J¼1.0, 6.9,
8.6 Hz, 8-H), 9.02 (1H, dd, J¼1.0, 6.9 Hz, 6-H); 13C NMR
(CDCl3): 16.6, 18.5 (CHMe2), 32.8 (CHMe2), 47.8
(CH2Ph), 51.4 (OMe), 58.3 (3-C), 81.3 (2-C), 92.0 (3a-C),
113.1 (7-C), 113.9, 118.4, 124.4, 127.1, 128.1, 128.4, 128.6,
129.1, 138.1, 147.2 (Ph–C and 6- and 9-C), 137.0 (8-C),
153.4, 153.5 (4- and 10a-C), 164.6 (9a-C), 170.5 (CO2Me).
Anal. calcd for C28H28N4O3 (468.5): C, 71.77; H, 6.02; N,
11.96. Found: C, 71.48; H, 6.01; N, 11.90.
129–1308C; IR (KBr): 3300 (NH), 1740, 1690 (CO); H
NMR (CDCl3): 3.33 (3H, s, OMe), 4.23 (1H, d, J¼7.6 Hz,
NHPh, exchanged with D2O), 4.61 (2H, br s, CH2Ph), 5.62
(1H, d, J¼7.6 Hz, 3-H), 6.54 (2H, br d, J¼7.6 Hz, Ph–H),
6.68 (1H, br t, J¼7.3 Hz, Ph–H), 6.97–7.48 (14H, ov,
Ph–H and 7- and 9-H), 7.68 (1H, ddd, J¼1.6, 5.9, 7.4 Hz,
8-H), 9.04 (1H, dd, J¼1.6, 6.3 Hz, 6-H); 13C NMR (CDCl3):
47.2 (CH2Ph), 51.6 (OMe), 66.3 (3-C), 81.0 (2-C), 91.1 (3a-
C), 114.2 (7-C), 118.3, 121.6, 124.6, 126.6, 127.5, 127.8,
128.0, 128.2, 128.4, 128.6, 128.8, 137.3, 137.8, 147.2
(Ph–C and 6- and 9-C), 138.8 (8-C), 153.5, 153.8 (4- and
10a-C), 163.9 (9a-C), 169.6 (CO2Me). Anal. calcd for
C31H26N4O3 (502.6): C, 74.08; H, 5.22; N, 11.15. Found: C,
73.88; H, 5.41; N, 11.27.
4.4.6. Methyl 3-anilino-1-benzyl-2-phenyl-4-oxo-1,2,3,4-
tetrahydropyrido[1,2-a]pyrrolo[2,3-d]pyrimidine-2-car-
boxylate (8e). Yellow prisms from benzene–hexane; mp
1
128–1298C; IR (KBr): 3360 (NH), 1720, 1690 (CO); H
4.4.3. Methyl 3-anilino-1-benzyl-2-isobutyl-4-oxo-
1,2,3,4-tetrahydropyrido[1,2-a]pyrrolo[2,3-d]pyrimi-
dine-2-carboxylate (6d). Pale yellow prisms from EtOAc–
hexane; mp 115–1178C; IR (KBr): 3300 (NH), 1735, 1690
(CO); 1H NMR (CDCl3): 0.67, 1.02 (each 3H, each d,
J¼6.6 Hz, CHMe2), 1.66 (1H, m, CH2CHMe2), 2.04 (1H,
dd, J¼5.9, 15.1 Hz, 2-CHHCHMe2), 2.27 (1H, dd, J¼6.6,
15.1 Hz, 2-CHHCHMe2), 3.21 (3H, s, OMe), 3.89 (1H, d,
J¼8.2 Hz, NHPh, exchanged with D2O), 4.67 (2H, br s,
CH2Ph), 5.34 (1H, d, J¼8.2 Hz, 3-H), 6.68–7.58 (12H, ov,
Ph–H and 7- and 9-H), 7.64 (1H, ddd, J¼0.6, 6.9, 8.6 Hz,
8-H), 9.01 (1H, dd, J¼0.6, 6.2 Hz, 6-H); 13C NMR (CDCl3):
23.5, 24.2, 24.5 (CHMe2 and 2-CH2CHMe2), 39.2
(2-CH2CHMe2), 46.2 (CH2Ph), 52.3 (OMe), 65.6 (3-C),
75.8 (2-C), 91.9 (3a-C), 113.2 (7-C), 113.3, 117.9, 124.2,
137.0, 127.1, 128.4, 128.9, 129.2, 139.1, 147.6 (Ph–C and
6- and 9-C), 137.1 (8-C), 153.5, 153.6 (4- and 10a-C), 163.7
(9a-C), 174.0 (CO2Me). Anal. calcd for C29H30N4O3
(482.6): C, 72.18; H, 6.27; N, 11.61. Found: C, 71.93; H,
6.32; N, 11.50.
NMR (CDCl3): 3.28 (3H, s, OMe), 3.46 (1H, d, J¼9.6 Hz,
NHPh, exchanged with D2O), 4.39, 5.20 (each 1H, each d,
J¼16.5 Hz, CH2Ph), 6.26 (1H, d, J¼9.6 Hz, 3-H), 6.44 (2H,
br d, J¼7.9 Hz, Ph–H), 6.57 (1H, br t, J¼7.9 Hz, Ph–H),
6.95–7.49 (14H, ov, Ph–H and 7- and 9-H), 7.71 (1H, ddd,
J¼1.6, 5.9, 7.4 Hz, 8-H), 9.01 (1H, br d, J¼6.7 Hz, 6-H);
13C NMR (CDCl3): 47.1 (CH2Ph), 52.4 (OMe), 60.0 (3-C),
81.3 (2-C), 95.0 (3a-C), 113.5 (7-C), 117.4, 124.6, 126.7,
127.0, 127.7, 128.0, 128.1, 128.2, 128.3, 128.4, 128.7,
133.4, 137.3, 146.8 (Ph–C and 6- and 9-C), 138.5 (8-C),
154.1, 154.3 (4- and 10a-C), 163.8 (9a-C), 171.4 (CO2Me).
Anal. calcd for C31H26N4O3 (502.6): C, 74.08; H, 5.22; N,
11.15. Found: C, 73.71; H, 5.22; N, 11.07. The structure of
8e was confirmed by X-ray crystal structure analysis.
4.5. Typical procedures for the reaction of N-benzyl-N-
(3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)glycine
methyl esters 3a–c with t-butylamine (9)
A solution of 3a (0.16 g, 0.46 mmol) and t-butylamine (9:
0.30 mL, 2.8 mmol) in benzene (20 mL) was heated at 508C
for 84 h. The solvent was evaporated to dryness to give a
residue, which was subjected to a usual work-up with a
silica-gel column chromatography to afford 10a (0.080 g,
43%) and 11a (0.025 g, 14%) with an eluent of hexane/
EtOAc (2:1), respectively.
4.4.4. Methyl 3-anilino-1-benzyl-2-isobutyl-4-oxo-
1,2,3,4-tetrahydropyrido[1,2-a]pyrrolo[2,3-d]pyrimi-
dine-2-carboxylate (8d). Pale yellow prisms from ben-
zene–hexane; mp 118–1198C; IR (KBr): 3300 (NH), 1740,
1690 (CO); 1H NMR (CDCl3): 0.69, 0.77 (each 3H, each d,
J¼6.3 Hz, 2-CH2CHMe2), 1.80–2.06 (3H, ov, 2-CH2-
CHMe2), 3.53 (3H, s, OMe), 3.99 (1H, d, J¼7.6 Hz,
NHPh, exchanged with D2O), 4.82, 4.98 (each 1H, each d,
J¼16.5 Hz, CH2Ph), 5.60 (1H, d, J¼7.6 Hz, 3-H), 7.14-7.40
(12H, ov, Ph–H and 7- and 9-H), 7.66 (1H, ddd, J¼1.0, 6.1,
7.4 Hz, 8-H), 9.01 (1H, dd, J¼1.0, 6.5 Hz, 6-H); 13C NMR
(CDCl3): 23.5, 24.2, 24.5 (2-CH2CHMe2 and 2-CH2-
CHMe2), 39.2 (2-CH2CHMe2), 46.2 (CH2Ph), 52.3
(OMe), 59.6 (3-C), 75.8 (2-C), 91.9 (3a-C), 113.2 (7-C),
113.3, 117.9, 124.2, 127.0, 127.1, 128.4, 128.9, 129.2,
139.1, 147.6 (Ph–C and 6- and 9-C), 137.1 (8-C), 153.5,
153.6 (4- and 10a-C), 163.7 (9a-C), 174.0 (CO2Me). Anal.
calcd for C29H30N4O3 (482.6): C, 72.18; H, 6.27; N, 11.61.
Found: C, 71.89; H, 6.32; N, 11.53.
4.5.1. Methyl 1-benzyl-3-(t-butylamino)-4-oxo-1,2,3,4-
tetrahydropyrido[1,2-a]pyrrolo[2,3-d]pyrimidine-2-car-
boxylate (10a). Colorless needles from hexane; 108–
1
1098C; IR (KBr): 3400 (NH), 1740, 1680 (CO); H NMR
(CDCl3): 1.16 (9H, s, 3-NHCMe3), 1.63 (1H, br, 3-
NHCMe3), 3.70 (3H, s, OMe), 3.90, 5.37 (each 1H, each
d, J¼15.2 Hz, CH2Ph), 4.19 [1H, d, J¼9.2 Hz (cis), 2-H],
4.86 [1H, d, J¼9.2 Hz (cis), 3-H], 6.98 (1H, dt, J¼1.3,
6.9 Hz, 7-H), 7.23–7.37 (5H, ov, Ph–H), 7.42 (1H, d,
J¼8.6 Hz, 9-H), 7.66 (1H, ddd, J¼1.0, 6.9, 8.6 Hz, 8-H),
9.01 (1H, d, J¼6.9 Hz, 6-H); 13C NMR (CDCl3): 29.4
(CMe3), 47.1 (CH2Ph), 50.9 (CMe3), 51.3 (OMe), 54.0
(3-C), 69.6 (2-C), 92.8 (3a-C), 113.2 (7-C), 124.3 (9-C),
127.6, 127.9, 128.4, 128.6, 136.6, 136.8 (Ph–C and 6- and
8-C), 153.3, 153.4 (4- and 10a-C), 164.3 (9a-C), 169.8
(CO2Me). Anal. calcd for C23H26N4O3 (406.5): C, 67.96; H,
6.45; N, 13.78. Found: C, 67.88; H, 6.71; N, 13.81.
4.4.5. Methyl 3-anilino-1-benzyl-2-phenyl-4-oxo-1,2,3,4-
tetrahydropyrido[1,2-a]pyrrolo[2,3-d]pyrimidine-2-car-
boxylate (6e). Yellow prisms from benzene–hexane; mp