W. M. De Borggraeve et al.
FULL PAPER
ind), 7.54 (d, J = 7 Hz, 1 H, 4i-H), 7.39 (d, J = 7 Hz, 1 H, 7i-H),
7.32–7.23 (m, 5 H, Ph-H), 7.23–7.22 (m, 1 H, 2i-H), 7.14 (t, J =
7 Hz, 1 H, 5i-H), 7.05 (t, J = 7 Hz, 1 H, 6i-H), 6.91 (t, J = 5 Hz,
1 H, C2NH or CONH), 6.40 (s, 1 H, 5-H), 6.13 (t, J = 5 Hz, 1 H,
Synthesis of 3-[(6-Chloro-3,4-dihydro-3-oxo-4-phenethylpyrazin-2-
yl)amino]-N-[2-(pyridin-2-yl)ethyl]propionamide (31): Yield 0.25 g
(54%). M.p. 130 °C. IR (KBr, assignment): ν = 3320 (NH), 1683
˜
1
(CO), 1635 (CO) cm–1. H NMR (400 MHz, CDCl3): δ = 8.43 (d,
CONH or C2NH), 4.89 (s, 2 H, NCH2), 3.65 (qd, J = 6 Hz, 2 H, J = 6 Hz, 1 H, 6Ј-H), 7.55 (td, J = 7 Hz, 2 Hz, 1 H, 4Ј-H), 7.27–
C2NHCH2), 3.54 (qd, J = 6 Hz, 2 H, NHCH2CH2ind), 2.90 (t, J 6.90 (m, 9 H, Ph-H + 5Ј-H + 3Ј-H + 2NH), 6.27 (s, 1 H, 5-H),
= 6 Hz, 2 H, CH2ind), 2.37 (t, J = 6 Hz, 2 H, CH2CO) ppm. 13C
NMR (100 MHz, CDCl3): δ = 171.1 (CO), 150.0 (C-3), 149.9 (C-
3.94 (t, J = 8 Hz, 2 H, NCH2), 3.68 (q, J = 8 Hz, 2 H, C2NHCH2),
3.60 (qd, J = 8 Hz, 2 H, CONHCH2), 2.96–2.76 (m, 4 H, CH2Ph
2), 136.3 (C-7ai), 134.7 (C-ipso Ph), 128.6, 128.1, 127.9 (Ph-C), + CH2pyr), 2.04 (t, J = 8 Hz, 2 H, CH2CO) ppm. 13C NMR
127.1 (C-3ai), 126.6 (C-6), 122.1 (C-2i), 121.2 (C-6i), 118.5 (C-5i), (100 MHz, CDCl3): δ = 170.9 (CO), 159.4 (C-ipso pyr), 150.2 (C-
118.0 (C-4i), 112.0 (C-5), 111.8 (C-3i), 111.0 (C-7i), 51.5 (NCH2), 3), 150.1 (C-2), 148.9, 137.2 (pyr-C), 136.7 (C-ipso Ph), 128.7,
39.8 (NHCH2CH2ind), 37.1 (NHCH2), 34.8 (CH2CO), 24.8 128.6, 126.8 (Ph-C), 126.4 (C-6), 123.4, 121.5 (pyr-C), 112.4 (C-5),
(CH2ind) ppm. EIMS {(relative intensity) [assignment]}: m/z (%) =
449 (29) [M+·], 91 (100) [PhCH2+]. HRMS (EI): calcd. for
C24H24ClN5O2 449.1618; found 449.1620.
50.7 (NCH2), 38.8 (CONHCH2), 37.3 (C2NHCH2), 36.9 (CH2pyr),
35.2 (CH2CO), 34.5 (CH2Ph) ppm. EIMS {(relative intensity)
[assignment]}: m/z (%) = 425 (95) [M+·], 105 (100) [PhCH2CH2+].
HRMS (EI): calcd. for C22H24ClN5O2 425.1601; found 425.1618.
Synthesis of 3-[(6-Chloro-3,4-dihydro-3-oxo-4-phenethylpyrazin-2-
yl)amino]-N-(pyridin-2-ylmethyl)propionamide (26): Yield 0.14 g
Synthesis of 3-[(6-Chloro-3,4-dihydro-3-oxo-4-phenethylpyrazin-2-
yl)amino]-N-[2-(1H-indol-3-yl)ethyl]propionamide (36): Yield 0.20 g
(30%). M.p. 145 °C. IR (KBr, assignment): ν = 3323 (NH), 1652
˜
(40%). Oil. IR (KBr, assignment): ν = 3648 (NH), 1684 (CO), 1652
˜
1
(CO) cm–1. H NMR (400 MHz, CDCl3 + CD3OD): δ = 8.05 (d,
(CO) cm–1. 1H NMR (400 MHz, CDCl3): δ = 8.95 (br. s, 1 H, NH-
ind), 7.49 (d, J = 7 Hz, 1 H, 4i-H), 7.27–7.11 (m, 6 H, Ph-H + 7i-
H), 7.10 (t, J = 7 Hz, 1 H, 5i-H), 7.00 (t, J = 7 Hz, 1 H, 6i-H), 6.94
(t, J = 7 Hz, 1 H, C2NH), 6.90 (s, 1 H, 2i-H), 6.24 (t, J = 5 Hz, 1
H, CONH), 6.18 (s, 1 H, 5-H), 3.84 (t, J = 8 Hz, 2 H, NCH2), 3.60
(q, J = 8 Hz, 2 H, C2NHCH2), 3.56 (qd, J = 6 Hz, 2 H,
CONHCH2), 2.85 (m, 4 H, CH2ind + CH2Ph), 2.34 (t, J = 6 Hz,
2 H, CH2CO) ppm. 13C NMR (100 MHz, CDCl3): δ = 171.0 (CO),
149.8 (C-2 and C-3), 136.9 (C-ipso Ph), 136.1 (C-7ai), 128.5, 128.4,
126.7 (Ph-C), 127.0 (C-3ai), 126.1 (C-6), 122.1 (C-2i), 121.5 (C-6i),
118.2 (C-4i), 118.8 (C-5i), 112.0 (C-5), 111.2 (C-7i), 50.4 (NCH2),
39.5 (CONHCH2), 37.0 (C2NHCH2), 34.8 (CH2CO), 34.2
(CH2Ph), 24.8 (CH2ind) ppm. EIMS {(relative intensity)
[assignment]}: m/z (%) = 463 (23) [M+·], 143 (100) [indCH=CH2+].
HRMS (EI): calcd. for C25H26ClN5O2 463.1775; found 463.1779.
J = 6 Hz, 1 H, 6Ј-H), 7.32 (td, J = 7 Hz, 2 Hz, 1 H, 4Ј-H), 6.93 (d,
J = Hz, 1 H, 3Ј-H), 6.88–6.76 (m, 6 H, Ph-H + 5Ј-H), 6.09 (s, 1 H,
5-H), 4.11 (s, 2 H, CH2pyr), 3.62 (t, J = 8 Hz, 2 H, NCH2), 3.31
(t, J = 6 Hz, 2 H, C2NHCH2), 2.57 (t, J = 8 Hz, 2 H, CH2Ph),
2.24 (t, J = 6 Hz, 2 H, CH2CO) ppm. 13C NMR (100 MHz, CDCl3
+ CD3OD): δ = 172.1 (CO), 157.1 (C-ipso pyr), 149.8 (C-3), 149.7
(C-2), 148.1, 137.1 (pyr-C), 136.9 (C-ipso Ph), 128.2, 128.1, 126.3
(Ph-C), 126.1 (C-6), 122.0, 121.4 (pyr-C), 112.4 (C-5), 50.2 (NCH2),
43.9 (CH2pyr), 36.8 (NHCH2), 34.4 (CH2CO), 33.9 (CH2Ph) ppm.
EIMS {(relative intensity) [assignment]}: m/z (%) = 411 (91) [M+·],
105 (100) [PhCH2CH2+]. HRMS (EI): calcd. for C21H22ClN5O2
411.1159; found 411.1462.
Synthesis of N-Benzyl-3-[(6-chloro-3,4-dihydro-3-oxo-4-phenethyl-
pyrazin-2-yl)amino]propionamide (16): Yield 0.30 g (34%). M.p.
132 °C. IR (KBr, assignment): ν = 3395 (NH), 1734 (CO), 1652
(CO). H NMR (400 MHz, CDCl3): δ = 7.30–7.13 (m, 10 H, Ph-
˜
Synthesis of N-Benzyl-2-[(4-benzyl-6-chloro-3,4-dihydro-3-oxopyr-
azin-2-yl)amino]-3-phenylpropionamide (12): Yield 0.35 g (50%).
1
H), 6.89 (t, J = 5 Hz, 1 H, C2NH), 6.68 (t, J = 5 Hz, 1 H, CONH),
6.28 (s, 1 H, 5-H), 4.37 (d, J = 6 Hz, 2 H, NHCH2Ph), 3.95 (t, J
= 8 Hz, 2 H, NCH2), 3.68 (qd, J = 6 Hz, 2 H, C2NHCH2), 2.95
(t, J = 8 Hz, 2 H, CH2Ph), 2.52 (t, J = 6 Hz, 2 H, CH2CO) ppm.
13C NMR (100 MHz, CDCl3): δ = 171.0 (CO), 150.1 (C-3), 150.0
(C-2), 138.2, 137.2 (C-ipso Ph), 128.8, 128.7, 128.6, 127.7, 127.4,
127.3, 126.9 (Ph-C), 126.4 (C-6), 112.5 (C-5), 50.7 (NCH2), 43.6
(C2NHCH2), 37.3 (CH2CO), 35.3 (CH2pyr), 34.6 (CH2Ph) ppm.
EIMS {(relative intensity) [assignment]}: m/z (%) = 410 (100) [M+·].
HRMS (EI): calcd. for C22H23ClN4O2 410.1505; found 410.1509.
Oil. IR (KBr, assignment): ν = 3384 (NH), 1683 (CO), 1635 (CO)
˜
1
cm–1. H NMR (400 MHz, CDCl3): δ = 7.28–7.04 (m, 15 H, Ph-
H), 6.94 (d, J = 7 Hz, 1 H, C2NH), 6.66 (t, J = 6 Hz, 1 H, CONH),
6.44 (s, 1 H, 5-H), 4.83 (s, 2 H, NCH2), 4.69 (q, J = 7 Hz, 1 H,
CHCO), 4.30 (dd, J = 14 Hz, 6 Hz, 1 H, NHCHA Ph), 4.26 (dd, J
= 14 Hz, 6 Hz, 1 H, NHCHB Ph), 3.15 (d, J = 7 Hz, 2 H, CHCH2
Ph) ppm. 13C NMR (100 MHz, CDCl3): δ = 170.3 (CO), 149.9 (C-
3), 149.4 (C-2), 137.6, 136.4, 134.4 (C-ipso Ph), 129.0, 128.7, 128.3,
128.2, 128.0, 127.1, 126.9, 126.6 (Ph-C), 126.1 (C-6), 113.0 (C-5),
56.3 (CHCO), 51.5 (NCH2), 43.0 (NHCH2Ph), 37.4 (CHCH2Ph)
ppm. EIMS {(relative intensity) [assignment]}: m/z (%) = 472 (24)
[M+·], 91 (100) [PhCH2+]. HRMS (EI): calcd. for C27H25ClN4O
472.1666; found 472.1668.
Synthesis of 3-[(6-Chloro-3,4-dihydro-3-oxo-4-phenethylpyrazin-2-
yl)amino]-N-(phenethyl)propionamide (21): Yield 0.41 g (62%). M.p.
138 °C. IR (KBr, assignment): ν = 3319 (NH), 1699 (CO), 1652
˜
1
(CO) cm–1. H NMR (400 MHz, CDCl3): δ = 7.29–7.14 (m, 10 H, Synthesis of 2-[(4-Benzyl-6-chloro-3,4-dihydro-3-oxopyrazin-2-yl)-
Ph-H), 6.85 (t, J = 6 Hz, 1 H, C2NH), 6.29 (s, 1 H, 5-H), 6.08 (t, amino]-3-phenyl-N-(phenethyl)propionamide (17): Yield 0.30 g
J = 5 Hz, 1 H, CONH), 3.95 (t, J = 8 Hz, 2 H, NCH2), 3.68 (qd,
J = 6 Hz, 2 H, C2NHCH2), 3.49 (qd, J = 7 Hz, 2 H, CONHCH2), 1H NMR (400 MHz, CDCl3): δ = 7.34–6.99 (m, 15 H, Ph-H), 6.76
(45%). Oil. IR (KBr, assignment): ν = 3365 (NH), 1652 (CO) cm–1.
˜
2.96 (t, J = 7 Hz, 2 H, CH2Ph), 2.79 (t, J = 7 Hz, 2 H,
NHCH2CH2Ph), 2.52 (t, J = 6 Hz, 2 H, CH2CO) ppm. 13C NMR
(100 MHz, CDCl3): δ = 170.9 (CO), 150.2 (C-3), 150.1 (C-2), 138.9,
(d, J = 7 Hz, 1 H, C2NH), 6.49 (s, 1 H, 5-H), 6.06 (t, J = 6 Hz, 1
H, CONH), 4.97 (d, J = 14 Hz, 1 H, NCHAPh), 4.88 (d, J = 14 Hz,
1 H, NCHB Ph), 4.59 (qd, J = 7 Hz, 1 H, CHCO), 3.49–3.35 (m,
137.2 (C-ipso Ph), 128.8, 128.7, 128.5, 126.9, 126.4 (Ph-C), 126.3 2 H, NHCH2), 2.71–2.62 (m, 2 H, NHCH2CH2), 3.15 (d, J = 7 Hz,
(C-6), 112.6 (C-5), 50.8 (NCH2), 40.6 (CONHCH2), 37.3 2 H, CHCH2 Ph) ppm. 13C NMR (100 MHz, CDCl3): δ = 170.1
(C2NHCH2), 35.6 (NHCH2CH2Ph), 35.4 (CH2CO), 34.6 (CH2Ph) (CO), 149.9 (C-3), 149.3 (C-2), 138.5, 136.4, 134.5 (C-ipso Ph),
ppm. EIMS {(relative intensity) [assignment]}: m/z (%) = 424 (100)
[M+·]. HRMS (EI): calcd. for C23H25ClN4O2 424.1663; found
424.1665.
129.1, 128.8, 128.5, 128.4, 128.2, 126.8, 126.3 (Ph-C), 126.2 (C-
6), 113.0 (C-5), 56.2 (CHCO), 51.8 (NCH2), 40.5 (NHCH2), 37.7
(CHCH2Ph), 35.2 (NHCH2CH2) ppm. EIMS {(relative intensity)
2984
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Eur. J. Org. Chem. 2007, 2977–2986