H. I. Al-Jaber et al. · Thienopyridone Antibacterials
1629
3H, J = 6.4, 6.4 Hz, CHCH3, Z/E), 3.56 (m, 3H, CH2OH + then stirred at r. t.◦for 30 min. The temperature was allowed
CHMe), 3.63, 3.64 (2s, 3H, OCH3, Z/E), 4.20 (br s, 1H, to rise to 60 – 62 C and maintained at that temperature for
CH2OH), 6.78, 6.89 (2s, 1H, 4ꢀꢀ-H, Z/E), 8.17, 7.99 (2d, 2 – 3 h. The solvent was then evaporated, and the residue was
1H, J = 14.4, 14.4 Hz, 3-H, Z/E), 10.83, 9.42 (2dd, 1H, J = washed with water. The solid product was purified by crys-
14.4, 6.4 Hz / 14.4, 6.4 Hz, NH, Z/E). – 13C NMR (75 MHz, tallization from the appropriate solvent.
CDCl3): δ = 17.0 (CHCH3), 51.4, 51.2 (OCH3, Z/E), 57.9,
57.5 (CHMe, Z/E), 65.9, 66.1 (CH2OH, Z/E), 100.7, 100.4
(C-2, Z/E), 124.6 (C-3ꢀꢀ), 126.0 (C-5ꢀꢀ), 126.3, 126.1 (C-4ꢀꢀ,
Z/E), 139.9 (C-2ꢀꢀ), 159.9, 159.7 (C-3, Z/E), 167.5, 169.1
(C-1, Z/E), 186.8 (C-4). – MS (EI, 70 eV): m/z (%) = 337
(2) [M]+, 302 (100), 270 (4), 242 (1), 179 (62), 144 (2),
116 (2), 59 (9). – C12H13NO4SCl2 (338.21): calcd. C 42.62,
H 3.87, N 4.14; found C 42.53, H 3.78, N 4.06.
Methyl 2-chloro-7-(4-methylpiperazin-1-yl)-4-oxo-4,7-di-
hydrothieno[2,3-b]pyridine-5-carboxylate (8a)
The obtained solid was recrystallized from chloro-
◦
form/methanol. Yield: 4.5 g (82 %), m. p. 210 – 211 C. –
1H NMR (300 MHz, CDCl3): δ = 2.39 (s, 3H, NCH3), 2.42
(br t, 2H, J = 10.5, 3ꢀ-H + 5ꢀ-H), 2.96 (br d, 2H, J = 10.2 Hz,
3ꢀ-H + 5ꢀ-H), 3.30 (br t, 2H, J = 10.2 Hz, 2ꢀ-H + 6ꢀ-H),
3.19 (br d, 2H, J = 10.5 Hz, 2ꢀ-H + 6ꢀ-H), 3.91 (s, 3H,
OCH3), 7.40 (s, 1H, 3-H), 8.58 (s, 1H, 6-H). – 13C NMR
(75 MHz, CDCl3): δ = 45.5 (NCH3), 52.4 (OCH3), 53.9
(C-3ꢀ + C-5ꢀ), 54.6 (C-2ꢀ + C-6ꢀ), 115.7 (C-5), 123.4 (C-3),
126.1 (C-4a), 131.5 (C-2), 139.2 (C-6), 149.2 (C-7a), 165.6
(CO2Me), 169.6 (C-4). – MS (EI, 70 eV): m/z (%) = 341
(74) [M]+, 242 (26), 211 (87), 183 (3), 99 (100), 56 (39),
53 (6). – C14H16N3O3SCl (341.82): calcd. C 49.19, H 4.72,
N 12.29; found C 48.99, H 4.69, N 11.99.
Methyl (S)-2-[(2,5-dichlorothien-3-yl)carbonyl]-3-N-(2-
hydroxy-1-methylethyl)acrylate (7f)
This compound was obtained as an oil. Yield: 5.7 g
(84 %). – C12H13NO4SCl2 (338.21): calcd. C 42.62, H 3.87,
N 4.14; found C 42.45, H 3.82, N 4.11. The spectral data
for this compound are in complete match with those of its
(R)-enantiomer.
Methyl (R)-2-[(2,5-dichlorothien-3-yl)carbonyl]-3-N-(2-
phenylethylamino)acrylate (7g)
Methyl 2-chloro-7-(morpholin-4-yl)-4-oxo-4,7-dihydro-
thieno[2,3-b]pyridine-5-carboxylate (8b)
The compound was recrystallized from benzene/
petroleum ether. Yield: 6.5 g (85 %), m. p. 93 – 94 ◦C. –
1H NMR (300 MHz, CDCl3): δ = 1.67, 1.65 (2d, 3H, J =
6.9, 6.9 Hz, CHCH3), 3.60, 3.64 (2s, 3H, OCH3, Z/E), 4.65,
4.06 (2m, 1H, CHMe), 6.80, 6.87 (2s, 1H, 4ꢀꢀ-H, Z/E), 7.37,
7.29 (2m, 5H, Ph), 8.13, 7.93 (2d, 1H, J = 14.3, 14.2 Hz,
3-H, Z/E), 11.20, 9.70 (2dd, 1H, J = 14.3, 6.9 Hz / 14.3,
6.9 Hz, NH). – 13C NMR (75 MHz, CDCl3): δ = 23.0
(CHCH3), 51.3, 51.2 (OCH3, Z/E), 59.3, 58.9 (CHMe, Z/E),
101.0, 100.8 (C-2, Z/E), 125.7 (C-3ꢀꢀ), 126.0 (C-3ꢀ + C-5ꢀ),
126.3, 125.9 (C-4ꢀꢀ, Z/E), 127.1 (C-5ꢀꢀ), 128.3 (C-4ꢀ), 129.1
(C-2ꢀ + C-6ꢀ), 139.9 (C-2ꢀꢀ), 141.1, 141.2 (C-1ꢀ, Z/E), 158.8,
159.1 (C-3, Z/E), 166.7, 169.0 (C-1, Z/E), 186.8, 183.9 (C-4,
Z/E). – MS (EI, 70 eV): m/z (%) = 383 (2) [M]+, 348 (51),
316 (1), 288 (2), 179 (11), 151 (2), 116 (1), 105 (100). –
C17H15NO3SCl2 (384.28): calcd. C 53.14, H 3.93, N 3.64;
found C 53.3, H 4.16, N 3.56.
The solid obtained was recrystallized from chloro-
form/petroleum ether. Yield: 4.8 g (91 %), m. p. 200 – 202 ◦C
(dec.). – 1H NMR (300 MHz, CDCl3): δ = 3.17 (br d, 2H, J =
10.3 Hz, 3ꢀ-H + 5ꢀ-H), 3.31 (dt, 2H, J = 10.2, J = 3.0, 3ꢀ-H +
5ꢀ-H), 3.81 (dt, 2H, J = 10.3, J = 3.0 Hz, 2ꢀ-H + 6ꢀ-H), 4.07
(br d, 2H, J = 10.3 Hz, 2ꢀ-H + 6ꢀ-H), 3.93 (s, 3H, OCH3),
7.40 (s, 1H, 3-H), 8.55 (s, 1H, 6-H). – 13C NMR (75 MHz,
CDCl3): δ = 52.5 (OCH3), 54.5 (C-3ꢀ + C-5ꢀ) , 66.8 (C-2ꢀ +
C-6ꢀ), 115.9 (C-5), 123.4 (C-3), 126.1 (C-4a), 131.6 (C-2),
138.9 (C-6), 148.9 (C-7a), 165.7 (CO2Me), 169.4 (C-4). –
MS (EI, 70 eV): m/z (%) = 328 (43) [M]+, 242 (3), 211
(14), 183 (5), 86 (35), 56 (100), 53 (11). – C13H13N2O4SCl
(328.78): calcd. C 47.49, H 3.99, N 8.52; found C 47.46,
H 3.69, N 8.48.
Methyl 2-chloro-4-oxo-7-(piperidin-1-yl)-4,7-dihydro-
thieno[2,3-b]pyridine-5-carboxylate (8c)
Preparation of methyl 7-(N-substituted amino)- and
7-alkyl-2-chloro-4-oxo-4,7-dihydrothieno[2,3-b]pyridine-5-
carboxylates 8a – g
The obtained solid was recrystallized from a mixture of
chloroform/diethyl ether. Yield: 4.6 g (88 %), m. p. 160 –
◦
162 C. – 1H NMR (300 MHz, CDCl3): δ = 1.84 (m, 6H,
General procedure
3ꢀ-H2 + 4ꢀ-H2 + 5ꢀ-H2), 3.01 (dt, 2H, J = 10.2, 2.1 Hz,
To a stirred solution of the particular methyl 3-(N- 2ꢀ-H + 6ꢀ-H), 3.28 (br d, 2H, J = 9.3 Hz, 2ꢀ-H + 6ꢀ-H),
substituted amino)- or methyl 3-(N-alkylamino)-2-[(2,5- 3.92 (s, 3H, OCH3), 7.40 (s, 1H, 3-H), 8.54 (s, 1H, 6-H). –
dichlorothien-3-yl)carbonyl]acrylate 7a – g (16 mmol) in dry 13C NMR (75 MHz, CDCl3): δ = 22.8 (C-4ꢀ), 26.1 (C-3ꢀ +
THF (70 mL) was added sodium hydride (80 % dispersion C-5ꢀ), 52.4 (OCH3), 55.7 (C-2ꢀ + C-6ꢀ), 115.6 (C-5), 123.3
in mineral oil; 0.5 g, 20 mmol). The reaction mixture was (C-3), 126.1 (C-4a), 131.5 (C-2), 139.2 (C-6), 149.4 (C-7a),
- 10.1515/znb-2009-11-1249
Downloaded from De Gruyter Online at 09/12/2016 11:11:47PM
via free access