A.A. Fesenko, A.D. Shutalev / Tetrahedron 67 (2011) 6876e6882
6881
2
3
DMSO-d6)
d
: 166.7, 166.5 (C]O in CH(COOEt)2), 154.1 (C(2)), 147.8
¼2.7 Hz, 4-H), 3.47 (1H, dd, J5-H(A),5-H(B)¼16.6, J5-H(A),4-
2 3
H(B)
(C(7)), 143.1 (C(4) in 4-MeC6H4), 139.1 (C(1) in 4-MeC6H4), 135.2 (C(1)
in Ph), 129.5 (C(3) and C(5) in 4-MeC6H4), 129.2 (br, C(2) and C(6) in
Ph), 129.0 (C(4) in Ph), 127.4 (C(3) and C(5) in Ph), 126.7 (C(2) and C(6)
in 4-MeC6H4), 115.1 (C(6)), 61.6, 61.4 (OCH2 in CH(COOEt)2), 55.3 (CH
in CH(COOEt)2), 50.9 (C(4)), 31.5 (C(5)), 21.0 (CH3 in Ts), 13.84, 13.82
¼5.7 Hz, 5-H(A)), 2.92 (1H, dd, J5-H(B),5-H(A)¼16.6, J5-H(B),4-
H
H
¼2.7 Hz, 5-H(B)), 2.34 (3H, s, CH3). 13C NMR (75.48 MHz, DMSO-
d6) d: 153.7 (C(2)), 147.8 (C(7)), 143.0 (C(4) in 4-MeC6H4), 139.1 (C(1) in
4-MeC6H4), 134.8 (C(1) in Ph), 129.3 (C(2) and C(6) in Ph), 129.2 (C(3)
and C(5) in 4-MeC6H4), 129.0 (C(4) in Ph), 127.4 (C(3) and C(5) in Ph),
126.9 (C(2) and C(6) in 4-MeC6H4), 118.1 (CN), 115.4 (C(6)), 42.1 (C(4)),
(CH3 in CH(COOEt)2). IR (Nujol)
NH), 3022w ( CHarom), 1756s, 1727m (
(amide-I), 1629s ( C]C), 1598m, 1492m (
1242m ( CeO), 1148s (ns SO2), 1088s ( CeO), 818m (
754m, 691m ( CH in Ph). Anal. Calcd for C25H28N2O7S: C, 59.99; H,
5.64; N, 5.60. Found: C, 59.67; H, 5.84; N, 5.57.
n
, cmꢂ1: 3249s, 3149m, 3112s (
C]O in COOEt), 1695s
CCarom), 1307s (nas SO2),
CHarom in Ts),
n
n
n
32.4 (C(5)), 21.0 (CH3). IR (Nujol)
NH), 3049w, 3029w ( CHarom), 2240vw (
1635s ( C]C), 1598m, 1492m ( CCarom), 1279s (nas SO2), 1143s (ns
SO2), 811m ( CHarom in Ts), 758m, 698m ( CH in Ph). Anal. Calcd for
n
, cmꢂ1: 3379s, 3278s, 3155m (
CN), 1688s (amide-I),
n
n
n
n
n
n
n
d
n
n
d
d
d
C19H17N3O3S: C, 62.11; H, 4.66; N, 11.44. Found: C, 62.33; H, 5.00; N,
11.44.
4.1.8. 7-Phenyl-4-phenylthio-6-tosyl-2,3,4,5-tetrahydro-1H-1,3-
diazepin-2-one (16). To a stirred suspension of NaH (0.011 g,
0.46 mmol) in MeCN (1 mL) was added a solution of thiophenol
(0.053 g, 0.48 mmol) in MeCN (1.5 mL), and the resulting white
suspension was stirred at rt for 10 min. Mesyloxymethylpyrimidine
9 (0.180 g, 0.41 mmol) and MeCN (0.5 mL) were added and the
obtained suspension was stirred at rt for 4 h. After the reaction was
complete the solvent was removed under vacuum, the oily residue
was triturated with light petrol (3 mL) and H2O (2 mL) under
cooling until complete crystallization. The formed suspension was
cooled, the precipitate was filtered, washed with ice-cold water,
light petrol, and dried to give crude 16 (0.173 g). In a similar manner
and in the same purity, compound 16 (0.880 g) was also prepared
from chloromethylpyrimidine 10 (0.765 g, 2.03 mmol), PhSH
(0.349 g, 3.17 mmol) and NaH (0.073 g, 3.04 mmol) in MeCN (10 mL)
(rt, 5 h). Crude product (0.310 g) was purified by column chroma-
tography on silica gel (15.1 g) using CHCl3/light petrol (1:2 to 70:30)
as eluent to give pure 16 in 65% overall yield (0.210 g). Mp
4.1.10. 7-Phenyl-4-phthalimido-6-tosyl-2,3,4,5-tetrahydro-1H-1,3-
diazepin-2-one (18). To a mixture of mesyloxymethylpyrimidine 9
(0.514 g, 1.18 mmol) and potassium phthalimide (0.320 g,
1.73 mmol) was added MeCN (10 mL) and the obtained suspen-
sion was refluxed under stirring for 15 min. In 1 min after the
beginning of the reaction, the solid substance dissolved and after
additional 2 min new precipitate occurred. After the reaction was
complete, the solvent was removed under vacuum, to the solid
residue was added H2O (5 mL) and the resulting mixture was
triturated until complete crystallization. The formed suspension
was cooled to 0 ꢀC, the precipitate was filtered, washed with ice-
cold water, light petrol, and dried to give 18 (0.528 g, 92%). Mp
250.5 ꢀC (decomp., DMF/ethanol, 1:1 v/v). 1H NMR (300.13 MHz,
4
DMSO-d6)
d
: 8.92 (1H, d, JN(1)H,N(3)H¼1.9 Hz, N(1)H), 7.83e7.92
4
(4H, m, CH in phthalimido group), 7.53 (1H, ddd, JN(3)H,N(1)
¼3JN(3)H,4-H¼1.9, JN(3)H,5-H(B)¼1.1 Hz, N(3)H), 7.34e7.48 (5H, m,
4
H
C(2)H and C(6)H in 4-MeC6H4, C(3)H, C(4)H and C(5)H in Ph),
92.5e93.5 ꢀC. 1H NMR (300.13 MHz, DMSO-d6)
d
: 8.67 (1H, d, 4JN(1)
7.22e7.29 (4H, m, C(3)H and C(5)H in 4-MeC6H4, C(2)H and C(6)H in
3
4
3
3
3
¼2.0 Hz, N(1)H), 8.18 (1H, dd, JN(3)H,4-H¼5.2, JN(3)H,N(1)
Ph), 5.28 (1H, ddd, J4-H,5-H(A)¼9.9, J4-H,5-H(B)¼3.2, J4-H,N(3)
H,N(3)H
2
3
¼2.0 Hz, N(3)H), 7.20e7.50 (12H, m, CHarom in Ph and SPh, C(2)
H
¼1.9 Hz, 4-H), 3.48 (1H, dd, J5-H(A),5-H(B)¼14.6, J5-H(A),4-
H
H
H
H
2 3
and C(6)H in 4-MeC6H4), 7.06e7.11 (2H, m, C(3)H and C(5)H in 4-
¼9.9 Hz, 5-H(A)), 3.09 (1H, ddd, J5-H(B),5-H(A)¼14.6, J5-H(B),4-
3
3
3
3
MeC6H4), 4.90 (1H, ddd, J4-H,5-H(A)¼7.0, J4-H,N(3)H¼5.2, J4-H,5-
¼3.2, J5-H(B),N(3)H¼1.1 Hz, 5-H(B)), 2.31 (3H, s, CH3). 13C NMR
2
3
¼2.7 Hz, 4-H), 3.33 (1H, dd, J5-H(A),5-H(B)¼15.9, J5-H(A),4-
(75.48 MHz, DMSO-d6) d: 166.9 (C]O in phthalimido group),
H(B)
2
3
¼7.0 Hz, 5-H(A)), 3.02 (1H, dd, J5-H(B),5-H(A)¼15.9, J5-H(B),4-
153.7 (C(2)), 149.4 (C(7)), 143.5 (C(4) in 4-MeC6H4), 138.4 (C(1) in 4-
MeC6H4), 134.9 (C(1) in Ph), 134.6 (C(4) and C(5) in phthalimido
group), 131.5 (C(1) and C(2) in phthalimido group), 129.7 (C(3) and
C(5) in 4-MeC6H4, C(2), C(6) and C(4) in Ph), 127.5 (C(3) and C(5) in
Ph), 127.0 (C(2) and C(6) in 4-MeC6H4), 123.2 (C(3) and C(6) in
phthalimido group), 116.6 (C(6)), 61.5 (C(4)), 30.7 (C(5)), 21.1
H
¼2.7 Hz, 5-H(B)), 2.34 (3H, s, CH3). 13C NMR (75.48 MHz, DMSO-
H
d6) d: 153.7 (C(2)), 147.6 (C(7)), 143.0 (C(4) in 4-MeC6H4), 139.1 (C(1) in
4-MeC6H4), 135.1 (C(1) in Ph), 133.0 (C(1) in SPh), 132.2 (C(2) and C(6)
in SPh), 129.34 (br, C(2) and C(6) in Ph), 129.25 (C(3) and C(5) in 4-
MeC6H4), 129.1 (C(3) and C(5) in SPh), 129.0 (C(4) in Ph), 127.6 (C(4)
in SPh), 127.4 (C(3) and C(5) in Ph), 127.0 (C(2) and C(6) in 4-MeC6H4),
(CH3). IR (Nujol)
NH), 3074w, 3062w
phthalimido group), 1688s (amide-I in diazepinone moiety),
1625s ( C]C), 1596m, 1505m, 1494w ( CCarom), 1321s (nas SO2),
1146s (ns SO2), 810s ( CHarom in Ts), 772m ( CH in Ph), 725s ( CH
in phthalimido group), 696s CH in Ph). Anal. Calcd
n
, cmꢂ1: 3316s, 3216m, 3178m, 3126m, 3095m (
CHarom), 1778m, 1724vs (amide-I in
n
115.7 (C(6)), 59.6 (C(4)), 35.5 (C(5)), 21.0 (CH3 in Ts). IR (Nujol)
3214s, 3201s, 3056s ( NH), 1685s (amide-I), 1627s ( C]C), 1597m,
1492m ( CCarom), 1300s (nas SO2), 1143s (ns SO2), 813m ( CHarom in
Ts), 748s, 696s ( CH in Ph and SPh). Anal. Calcd for C24H22N2O3S2:
n
, cmꢂ1
:
(n
n
n
n
d
n
n
d
d
d
d
C, 63.98; H, 4.92; N, 6.22. Found: C, 63.82; H, 5.06; N, 6.51.
(d
for C26H21N3O5S: C, 64.05; H, 4.34; N, 8.62. Found: C, 64.12; H,
4.52; N, 8.61.
4.1.9. 4-Cyano-7-phenyl-6-tosyl-2,3,4,5-tetrahydro-1H-1,3-diazepin-
2-one (17). To a mixture of mesyloxymethylpyrimidine 9 (0.508 g,
1.16 mmol) and finely powdered NaCN (0.074 g, 1.51 mmol) was
added dry DMF (1 mL). The obtained suspension was stirred at rt for
1 h 32 min, then ice-cold water (10 mL) was added and the solid
residue was triturated until complete crystallization. Upon cooling
to 0 ꢀC, the precipitate was filtered, washed with ice-cold water,
light petrol, ether/light petrol mixture (1:1 v/v, 2ꢁ3 mL), and dried
to give crude 17 (0.401 g). Crude product (0.332 g) was purified by
column chromatography on silica gel (16.7 g) using CHCl3/MeOH
(60:1) as eluent to give pure 17 in 65% overall yield (0.231 g). Mp
224.5e225 oC (decomp., ethanol). 1H NMR (300.13 MHz, DMSO-d6)
4.1.11. 7-Methyl-4-phthalimido-6-tosyl-2,3,4,5-tetrahydro-1H-1,3-
diazepin-2-one (19). Compound 19 was prepared (analogously to
18) from mesyloxymethylpyrimidine 14 (0.350 g, 0.93 mmol) and
potassium phthalimide (0.253 g, 1.37 mmol) in MeCN (5 mL, reflux,
15 min) (0.369 g, 93%) or from chloromethylpyrimidine 11 (0.057 g,
0.18 mmol) and potassium phthalimide (0.051 g, 0.28 mmol) in
MeCN (1 mL, reflux, 53 min) (0.065 g, 84%). Mp 240.5 ꢀC (decomp.,
DMF/ethanol, 1:2 v/v). 1H NMR (300.13 MHz, DMSO-d6)
d: 8.88 (1H,
d, 4JN(1)H,N(3)H¼1.8 Hz, N(1)H), 7.80e7.88 (4H, m, CH in phthalimido
group), 7.59e7.65 (2H, m, AA0 part of AA0XX0 spin system, C(2)H and
4
3
3
4
d
: 8.86 (1H, d, JN(1)H,N(3)H¼1.9 Hz, N(1)H), 8.28 (1H, dd, JN(3)H,4-
C(6)
H
in 4-MeC6H4), 7.53 (1H, dd, JN(3)H,4-H¼2.7, JN(3)H,N(1)
4
¼6.7, JN(3)H,N(1)H¼1.9 Hz, N(3)H), 7.31e7.37 (1H, m, CHpara in Ph),
¼1.8 Hz, N(3)H), 7.24e7.30 (2H, m, XX0 part of AA0XX0 spin system,
H
H
3
3
7.18e7.29 (6H, m, CHmeta in Ph and CHarom in Ts), 6.95e7.04 (2H, m,
C(3)H and C(5)H in 4-MeC6H4), 5.27 (1H, ddd, J4-H,5-H(A)¼9.1, J4-
3
3
3
3
2
CHortho in Ph), 4.87 (1H, ddd, J4-H,N(3)H¼6.7, J4-H,5-H(A)¼5.7, J4-H,5-
¼2.7, J4-H,5-H(B)¼2.5 Hz, 4-H), 3.23 (1H, dd, J5-H(A),5-
H,N(3)H