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Z. Szakonyi et al. / Tetrahedron 61 (2005) 1595–1602
19.4; 21.6; 28.0; 48.1; 49.3; 126.3; 128.3; 128.9; 137.7; and
169.7.
4.40–4.49 (1H, m, OCH); 4.65–4.66 (1H, m, NC]CH); and
7.20–7.39 (5H, m, C6H5). 13C NMR (75 MHz, CDCl3): 21.8
(NCH2(CH2)2); 32.2 (NCCH2); 40.8 (CH2C6H5); 42.9
(CH2N); 76.5 (OCH); 104.1 (NC]CH); 127.0 (HCpara);
128.7 and 129.6 (2!HCortho and 2!HCmeta); 131.0
(NC]CH); 136.0 (Carom,quat); and 151.3 (C]O). MS
(70 eV) m/z (%): 243 (MC, 85); 199 (12); 198 (57); 184
(5); 170 (5); 122 (18); 108 (100); 97 (14); and 91 (33). Anal.
calcd for C15H17NO2 (243.30): C, 74.05; H, 7.04; N, 5.76;
found C, 73.95; H, 7.14; N, 5.85.
4.2. Synthesis of 3-alkyl-4,6,7,8-tetrahydro-3H-pyrido
[1,2-c][1,3]oxazin-1-ones 11a–f. As a representative
example, the synthesis of 3-methyl-4,6,7,8-tetrahydro-3H-
pyrido[1,2-c][1,3]oxazin-1-one 11a is described. To a
solution of Me3SiI (3.00 g, 15 mmol) and phenol (1.41 g,
15 mmol) in CH2Cl2 (40 mL), tert-butyl (2E)-2-(2-propenyl-
idene)piperidine-1-carboxylate 3a (2.23 g, 10 mmol) in
CH2Cl2 (10 mL) was added at room temperature, and the
resulting mixture was stirred for 30 min. The reaction
mixture was then poured into 4 N NaOH solution (20 mL),
extracted with CH2Cl2 (3!20 mL), dried (MgSO4), filtered
and evaporated in vacuo, furnishing crude 3-methyl-4,6,7,8-
tetrahydro-3H-pyrido[1,2-c][1,3]oxazin-1-one 11a, which
was purified by column chromatography with petrol ether/
EtOAc (3/2), yielding pure 11a (0.69 g, 41%).
4.2.4. 3-Isopropyl-4,6,7,8-tetrahydro-3H-pyrido[1,2-
c][1,3]oxazin-1-one 11d. Flash chromatography (petrol
ether/EtOAc 3/2, RfZ0.60). Yield: 48%, yellow oil. IR
(NaCl, cmK1): nC]OZ1677. 1H NMR (300 MHz, CDCl3):
d 0.96 and 1.02 (6H, 2!d, JZ6.9 Hz, (CH3)2); 1.75–1.94
(3H, m, NCH2CH2 and CHMe2); 2.05–2.12 (2H, m,
N(CH2)2CH2); 2.33–2.53 (2H, m, NCCH2); 3.46 (1H, ddd,
JZ4.1, 8.8, 12.9 Hz, (HCH)N); 3.89–3.97 (2H, m, (HCH)N
and OCH); and 4.68–4.71 (1H, m, NC]CH). 13C NMR
(75 MHz, CDCl3): 17.7 and 17.8 ((CH3)2); 21.8
(NCH2(CH2)2); 30.3 (NCCH2); 32.8 (CHMe2); 42.8
(CH2N); 80.7 (OCH); 103.5 (NC]CH); 131.5 (NC]CH);
and 151.9 (C]O). MS (70 eV) m/z (%): 195 (MC, 42); 150
(26); 136 (100); 122 (10); 110 (12); 108 (32); 94 (10); 80
(6); 55 (10); and 54 (8). Anal. calcd for C11H17NO2
(195.26): C, 67.66; H, 8.78; N, 7.17; found C, 67.51; H,
8.85; N, 7.28.
4.2.1.
3-Methyl-4,6,7,8-tetrahydro-3H-pyrido[1,2-
c][1,3]oxazin-1-one 11a. Flash chromatography (petrol
ether/EtOAc 3/2, RfZ0.25). Yield: 41%, pale-yellow oil.
IR (NaCl, cmK1): nC]OZ1666. 1H NMR (300 MHz,
CDCl3): d 1.36 (3H, d, JZ6.1 Hz, CH3); 1.80–1.98 (2H,
m, NCH2CH2); 2.02–2.08 (2H, m, N(CH2)2CH2); 2.29–2.51
(2H, m, NCCH2); 3.52 (1H, ddd, JZ4.8, 8.1, 12.9 Hz,
(HCH)N); 3.84–3.93 (1H, m, (HCH)N); 4.34–4.44 (1H, m,
CHO); and 4.70 (1H, br s, NC]CH). 13C NMR (75 MHz,
CDCl3): 20.42 (CH3); 21.8 (NCH2(CH2)2); 34.9 (NCCH2);
42.9 (CH2N); 72.4 (OCH); 103.7 (NC]CH); 130.4
(NC]CH); and 151.2 (C]O). MS (70 eV) m/z (%): 167
(MC, 70); 122 (100); 108 (40); 95 (42); 94 (21); 82 (26); 80
(25); 67 (13); 55 (20); 54 (29); and 41 (13). Anal. calcd for
C9H13NO2 (167.21): C, 64.65; H, 7.84; N, 8.38; found C,
64.76; H, 7.95; N, 8.31.
4.2.5. 3-Isobutyl-4,6,7,8-tetrahydro-3H-pyrido[1,2-c]
[1,3]oxazin-1-one 11e. Flash chromatography (petrol
ether/EtOAc 3/2, RfZ0.62). Yield: 70%, yellow oil. IR
(NaCl, cmK1): nC]OZ1673. 1H NMR (300 MHz, CDCl3):
d 2!0.93 (6H, 2!d, JZ6.6 Hz, (CH3)2); 1.62–1.71 (2H,
m, CH2CHMe2); 1.79–1.92 (3H, m, NCH2CH2 and
CHMe2); 2.05–2.07 (2H, m, N(CH2)2CH2); 2.27–2.50
(2H, m, NCCH2); 3.51 (1H, ddd, JZ4.8, 8.1, 12.9 Hz,
(HCH)N); 3.88 (1H, ddd, JZ4.8, 5.3, 12.9 Hz, (HCH)N);
4.26–4.35 (1H, m, OCH); and 4.69 (1H, br s, NC]CH). 13C
NMR (75 MHz, CDCl3): 21.7 and 21.8 (NCH2(CH2)2); 22.1
and 22.9 (CH3)2); 23.9 (CHMe2); 33.6 (NCCH2); 42.9 and
43.5 (CH2CHMe2 and CH2N); 74.4 (OCH); 103.6
(NC]CH); 131.3 (NC]CH); and 151.7 (C]O). MS
(70 eV) m/z (%): 209 (MC, 58); 164 (15); 152 (23); 150
(55); 122 (100); 108 (19); and 97 (47). Anal. calcd for
C12H19NO2 (209.14): C, 68.87; H, 9.15; N, 6.69; found C,
68.76; H, 9.27; N, 6.80.
4.2.2. 3-Ethyl-4,6,7,8-tetrahydro-3H-pyrido[1,2-c][1,3]
oxazin-1-one 11b. Flash chromatography (petrol ether/
EtOAc 3/2, RfZ0.44). Yield: 52%, yellow oil. IR (NaCl,
1
cmK1): nC]OZ1674. H NMR (300 MHz, CDCl3): d 1.00
(3H, t, JZ7.4 Hz, CH3); 1.70–1.80 (2H, m, CH3CH2); 1.80–
1.97 (2H, m, NCH2CH2); 2.04–2.14 (2H, m, N(CH2)2CH2);
2.22–2.51 (2H, m, NCCH2); 3.50 (1H, ddd, JZ4.4, 8.5,
12.9 Hz, (HCH)N); 3.89 (1H, ddd, JZ4.4, 5.4, 12.9 Hz,
(HCH)N); 4.09–4.21 (1H, m, CHO); and 4.69 (1H, br s,
NC]CH). 13C NMR (75 MHz, CDCl3): 9.3 (CH3); 21.8
and 21.9 (NCH2(CH2)2); 27.5 (CH2CH3); 32.7 (NCCH2);
42.9 (CH2N); 77.3 (OCH); 103.6 (NC]CH); 131.4
(NC]CH); and 151.7 (C]O). MS (70 eV) m/z (%): 181
(MC, 88); 152 (8); 136 (87); 122 (100); 108 (49); 96 (17);
95 (20); 94 (32); 82 (22); 81 (16); 80 (24); 67 (13); 55 (23);
54 (22); and 41 (14). Anal. calcd for C10H15NO2 (181.23):
C, 66.27; H, 8.34; N, 7.73; found C, 66.41; H, 8.24; N, 7.61.
4.2.6. 3-(4-Methoxybenzyl)-4,6,7,8-tetrahydro-3H-pyr-
ido[1,2-c][1,3]oxazin-1-one 11f. Flash chromatography
(petrol ether/EtOAc 3/2, RfZ0.42). Yield: 46%, oil. IR
(NaCl, cmK1): nC]OZ1684. 1H NMR (300 MHz, CDCl3):
d 1.77–1.91 (2H, m, NCH2CH2); 1.99–2.12 (2H, m,
N(CH2)2CH2); 2.26–2.43 (2H, m, NCCH2); 2.79 and 3.04
(2H, 2!dd, JZ5.2, 7.7, 13.8 Hz, (HCH)C6H5); 3.51 (1H,
ddd, JZ4.3, 8.5, 12.8 Hz, (HCH)N); 3.80 (3H, s, OCH3);
3.87 (1H, ddd, JZ4.3, 5.2, 12.9 Hz, (HCH)N); 4.35–4.44
(1H, m, OCH); 4.64 (1H, br s, NC]CH); 6.83–6.86 (2H, m,
2!HCortho); and 7.11–7.15 (2H, m, 2!HCmeta). 13C NMR
(75 MHz, CDCl3): 21.8 (NCH2(CH2)2); 32.1 (NCCH2);
39.8 (CH2C6H5); 42.9 (CH2N); 55.4 (OCH3); 76.7 (OCH);
103.9 (NC]CH); 114.1 (2!HCortho); 130.6 (2!HCmeta);
127.9 and 131.1 (NC]CH and Carom,quat); and 158.7
4.2.3. 3-Benzyl-4,6,7,8-tetrahydro-3H-pyrido[1,2-c][1,3]
oxazin-1-one 11c. Flash chromatography (petrol ether/
EtOAc 3/2, RfZ0.58). Yield: 60%, white crystals, mp 186–
188 8C. IR (NaCl, cmK1): nC]OZ1673. 1H NMR
(300 MHz, CDCl3): d 1.79–1.89 (2H, m, NCH2CH2);
2.05–2.17 (2H, m, N(CH2)2CH2); 2.30–2.44 (2H, m,
NCCH2); 2.85 and 3.11 (2H, 2!dd, JZ5.4, 7.7, 13.7 Hz,
(HCH)C6H5); 3.52 (1H, ddd, JZ4.3, 8.5, 12.9 Hz,
(HCH)N); 3.87 (1H, ddd, JZ4.3, 5.9, 12.9 Hz, (HCH)N);