Synthesis of Pyrrolo-[2,1-j]quinolone Framework via Intramolecular Electrophilic ipso-Cyclization
Lila Low-Beinart, Xiaohan Sun, Eli Sidman and Tanay Kesharwani* Chemistry Program, Bard College, PO Box 5000, Annandale-on-Hudson NY, 12504
[email protected]
Table of Contents Pages General
S2-S2
Reagents
S2-S2
General procedure for the preparation of amides 2 and 3
S2-S3
Synthesis of 6-methoxy-3,4-dihydroquinoline-1(2H)-carbonyl chloride (4)
S3-S4
General procedure for the preparation of amides 5, 6, 7, 8 and 9
S4-S6
General procedure for reaction conditions A
S6-S9
General procedure for the preparation of 19, 20
S9-S10
1
H and 13C NMR spectra
S11-S44
S1
General. The 1H and 13C NMR spectra were recorded at 400 and 100 MHz. Flash chromatography was performed on silica gel (200-400 mesh, 60 Å pore size). Thin layer chromatography was performed using commercially prepared 60-mesh silica gel plates, and visualization was effected with short wavelength UV light (254 nm). All melting points are uncorrected.
Reagents. All reagents were used directly as obtained commercially unless otherwise noted. General procedure for the preparation of amides 2 and 3. To a 6 dram vial containing a stir bar, 6-methoxytetrahydroquinoline (160 mg, 1.0 mmol), 3-phenyl-2propynoic acid (146.1 mg, 1.0 mmol) or 2-octynoic acid (140.18 mg, 1.0 mmol), and HATU (380 mg, 1.0 mmol) were added. The vial was purged with N2 and anhydrous THF (6 mL) added via syringe. Diisopropyl ethylamine (774 mg, 6.0 mmol) was then added dropwise to the reaction mixture. The reaction was stirred for 24 hours and periodically monitored by TLC. The reaction mixture was then diluted with 10 mL water and extracted with DCM (3 x 20 mL). After drying the organic layer with Na2SO4 the mixture was concentrated under vacuum to give crude product. Pure product was obtained using column chromatography using hexanes and ethyl acetate as eluent.
1-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)-3-phenylprop-2-yn-1-one (2). The product was obtained as an equimolar mixture of two rotamers. It was obtained as a beige crystalline solid (233 mg, 80%): mp 57-59 oC; 1H NMR (400 MHz, CDCl3) δ 7.99 (d, J = 9.0 Hz, 1H), 7.61 (t, J = 8.9 Hz, 3H), 7.43-7.30 (m, 8H), 6.79-6.67 (m, 4H), 4.12 (t, J = 5.8 Hz, 2H), 3.89 (t, J = 6.5 Hz, 2H), 3.82 (s, 3H), 3.79 (s, 3H), 2.87 (t, J = 6.9 Hz, 2H), 2.76 (t, J = 6.6 Hz, 2H), 2.08 (t, J = 6.0 Hz, 2H), 1.99 (t, J = 6.6 Hz, 2H);
13
C NMR (101 MHz, CDCl3) δ 157.5, 156.5, 153.3, 153.0, 134.2, 132.44, 132.40, S2
131.0, 130.9, 130.3, 130.1, 130.0, 128.5, 128.4, 125.7, 125.5, 120.64, 120.59, 113.7, 112.9, 111.7, 111.3, 91.3, 89.8, 83.4, 82.5, 55.5, 55.4, 47.4, 42.7, 29.7, 27.2, 27.1, 23.62, 23.58; HRMS (ESI+, m/z) calcd for (C19H18NO2)+ (M + H)+ 292.1333, found 292.1326.
1-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)oct-2-yn-1-one (3). The product was obtained as an equimolar mixture of two rotamers. It was obtained as an orange liquid (263 mg, 92%); 1H NMR (CDCl3) δ 7.91 (d, J = 9.0 Hz, 1H), 7.50 (d, J = 8.5 Hz, 1H), 6.75-6.64 (m, 4H), 4.02 (t, J = 5.7 Hz, 2H), 3.83-3.77 (m, 8H), 2.83 (t, J = 7.0 Hz, 2H), 2.71 (t, J = 6.7 Hz, 2H), 2.40 (t, J = 7.2 Hz, 2H), 2.25 (t, J = 7.1 Hz, 2H), 2.05-1.90 (m, 4H), 1.64-1.61 (m, 2H), 1.49-1.25 (m, 10H), 0.93-0.85 (m, 6H);
13
C NMR (101 MHz, CDCl3) δ 157.4, 156.5, 153.6, 153.4, 134.2, 131.3, 130.9, 130.6, 125.9,
125.7, 113.8, 113.1, 111.7, 111.2, 94.5, 93.5, 75.7, 75.1, 55.5, 47.4, 42.7, 31.2, 31.1, 27.7, 27.3, 23.7, 22.3, 19.23, 19.17, 14.1; HRMS (ESI+, m/z) calcd for (C18H24NO2)+ (M + H)+ 286.1802, found 286.1793.
Synthesis of 6-methoxy-3,4-dihydroquinoline-1(2H)-carbonyl chloride (4). In a 50 mL roundbottom flask purged with N2, 6-methoxytetrahydroquinoline (5.0 mmol, 820 mg), anhydrous DCM (10 mL) and N,N-diisopropylethylamine (10.0 mmol, 1.29 g) were added. In another 100 mL roundbottom flask equipped with a stir bar, anhydrous DCM (20 mL) and phosgene (7.5 mmol, 5.4 mL, 15 wt. % in toluene) were added and the resulting mixture was cooled to 0 oC. Contents of the first flask were added dropwise to the second flask. The reaction was warmed to room temperature and was allowed to stir for 24 hours. The reaction mixture was then quenched with 0.1M HCL and was extracted with DCM (3 x 70 mL). After drying the organic layer with Na2SO4, the mixture was concentrated under vacuum to give crude product. The pure product was obtained using column chromatography using 4:1 hexanes/ethyl acetate as the eluent. The product was isolated as a light pink
S3
crystalline solid (905 mg, 80%): mp 38-41. (Caution! Since the toxic gas phosgene is employed in this experiment, all steps should be performed in an efficient hood. Gloves, apron and safety glasses should be worn all the time. The glassware, which may be coated with a solution of phosgene, should be washed before it is removed from the hood); 1H NMR (400 MHz, CDCl3) δ 7.56 (s, 1H), 6.75 (dd, J = 9.0, 2.9 Hz, 1H), 6.66 (d, J = 2.8 Hz, 1H), 3.91 (t, J = 6.2 Hz, 2H), 3.79 (s, 3H), 2.78 (t, J = 6.7 Hz, 2H), 2.02 (p, J = 6.5 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ 157.4, 148.8, 130.9, 125.8, 113.4, 112.0, 55.5, 49.0, 27.1, 23.8. HRMS (ESI+, m/z) calcd for (C11H13ClNO2)+ (M + H)+ 226.0630, found 226.0622.
General procedure for the preparation of amides 5-9. Under inert conditions in a vial containing alkyne (2.0 mmol), anhydrous THF (2 mL) was added. The reaction mixture was then cooled to -78 oC and n-butyllithium (2.0 mmol, 0.8 mL, 2.5M in hexanes) was added. The reaction was allowed to stir for 2 hour at -78 oC and compound 4 (225 mg, 1.0 mmol) dissolved in anhydrous THF (3 mL) was added to the reaction mixture. The reaction was allowed to warm to 0 oC and was periodically monitored by TLC. After the reaction was completed, it was diluted with water (10 mL) and extracted with DCM (3 x 20 mL). After drying the organic layer with Na2SO4, the mixture was concentrated under vacuum to give crude product. The pure product was obtained using column chromatography using hexanes and ethyl acetate as the eluent.
1-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)-3-(p-tolyl)prop-2-yn-1-one (5).
The product was
obtained as an equimolar mixture of two rotamers. It was obtained as a light orange solid (178 mg, 58%): mp 88-89 oC; 1H NMR (400 MHz, CDCl3) δ 7.97 (d, J = 9.0 Hz, 1H), 7.60 (d, J = 8.8 Hz, 1H), 7.46 (d, J = 7.7 Hz, 2H), 7.29 (d, J = 7.7 Hz, 2H), 7.16 (d, J = 7.7 Hz, 2H), 7.10 (d, J = 7.8 Hz, 2H), 6.80-6.61 (m, 4H), 4.10 (t, J = 5.8 Hz, 2H), 3.86 (t, J = 6.5 Hz, 2H), 3.79 (s, 3H), 3.76 (s, 3H), 2.83 (t,
S4
J = 6.8 Hz, 2H), 2.73 (t, J = 6.6 Hz, 2H), 2.36 (s, 3H), 2.33 (s, 3H), 2.12-1.89 (m, 4H). 13C NMR (101 MHz, CDCl3) δ 157.5, 156.5, 153.4, 153.2, 140.59, 140.55, 134.2, 132.4, 131.0, 130.9, 130.3, 129.3, 129.2, 125.7, 125.5, 117.53, 117.48, 113.6, 112.9, 111.7, 111.3, 91.7, 90.3, 83.0, 82.1, 55.5, 55.4, 47.4, 42.7, 27.2, 23.6, 21.7; HRMS (ESI+, m/z) calcd for (C20H20NO2)+ (M + H)+ 306.1489, found 306.1480.
1-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)-3-(4-methoxyphenyl)prop-2-yn-1-one
(6).
The
product was obtained as an equimolar mixture of two rotamers. It was obtained as a beige solid (235 mg, 73%): mp 100-101 oC; 1H NMR (400 MHz, CDCl3) δ 7.97 (d, J = 9.2 Hz, 1H), 7.62 (d, J = 8.8 Hz, 1H), 7.53 (d, J = 8.3 Hz, 2H), 7.35 (d, J = 8.4 Hz, 2H), 6.91-6.66 (m, 8H), 4.11 (t, J = 4.0 Hz, 2H), 3.97-3.75 (m, 14H), 2.85 (t, J = 6.8 Hz, 2H), 2.75 (t, J = 6.6 Hz, 2H), 2.10-1.90 (m, 4H);
13
C
NMR (101 MHz, CDCl3) δ 161.1, 157.5, 156.5, 153.6, 153.4, 134.3, 134.2, 131.2, 130.9, 130.4, 125.8, 125.6, 114.3, 114.2, 113.7, 112.9, 112.6, 111.7, 111.4, 91.9, 90.5, 82.8, 81.8, 55.5, 55.4, 47.4, 42.7, 29.8, 27.3, 23.7; HRMS (ESI+, m/z) calcd for (C20H20NO3)+ (M + H)+ 322.1438, found 322.1424.
1-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)-3-(thiophen-3-yl)prop-2-yn-1-one (7). The product was obtained as an equimolar mixture of two rotamers. It was obtained as a light brown crystalline solid (197 mg, 66%): mp 81-82 oC; 1H NMR (400 MHz, CDCl3) δ 7.97 (d, J = 9.1 Hz, 1H), 7.71 (s, 1H), 7.62-7.52 (m, 2H), 7.40-7.23 (m, 3H) 7.07 (d, J = 5.2 Hz, 1H), 6.76 (dd, J = 9.0, 2.9 Hz, 2H), 6.68 (d, J = 18.4 Hz, 2H), 4.09 (t, J = 4.0 Hz, 2H), 3.87 (t, J = 4.0 Hz, 2H), 3.82 (s, 3H), 3.78 (s, 3H), 2.86 (t, J = 6.5 Hz, 2H), 2.75 (t, J = 6.5 Hz, 2H), 2.11-1.94 (m, 4H).
13
C NMR (101 MHz, CDCl3) δ
157.6, 156.6, 153.4, 153.1, 134.3, 132.4, 132.3, 131.00, 130.95, 130.3, 130.0, 129.9, 126.1, 125.9, 125.7, 125.5, 119.9, 119.8, 113.7, 113.0, 111.7, 111.3, 86.8, 85.5, 83.3, 82.4, 55.5, 55.4, 47.5, 42.7,
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29.8, 27.24, 27.21, 23.7, 23.6; HRMS (ESI+, m/z) calcd for (C17H16NO2S)+ (M + H)+ 298.0897, found 298.0888.
3-(cyclohex-1-en-1-yl)-1-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)prop-2-yn-1-one (8).
The
product was obtained as an equimolar mixture of two rotamers. It was obtained as a brown liquid (145 mg, 49%); 1H NMR (400 MHz, CDCl3) δ 7.93 (d, J = 9.0 Hz, 1H), 7.52 (d, J = 8.8 Hz, 1H), 6.74-6.67 (m, 4H), 6.40 (s, 1H), 6.23 (s, 1H), 4.01 (t, J = 5.9 Hz, 2H), 3.84-3.77 (m, 8H), 2.77 (t, J = 7.2, Hz, 2H), 2.71(t, J = 6.5, Hz, 2H), 2.20-1.93 (m, 12H), 1.67-1.54 (m, 8H); 13C NMR (101 MHz, CDCl3) δ 157.4, 156.5, 153.7, 153.5, 140.4, 140.2, 134.1, 131.3, 130.9, 130.5, 125.8, 125.6, 119.3, 115.7, 115.0, 113.7, 112.9, 111.7, 111.4, 93.6, 92.2, 81.3, 80.4, 55.6, 55.5, 47.4, 42.7, 28.5, 28.0, 27.3, 26.0, 23.7, 22.10, 22.05, 21.3; HRMS (ESI+, m/z) calcd for (C19H22NO2)+ (M + H)+ 296.1646, found 296.1637.
1-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)-4,4-dimethylpent-2-yn-1-one (9). The product was obtained as an equimolar mixture of two rotamers. It was obtained as a light brown liquid (142 mg, 52%); 1H NMR (400 MHz, CDCl3) δ 7.90 (d, J = 9.0 Hz, 1H), 7.52 (d, J = 8.4 Hz, 1H), 6.74-6.63 (m, 4H), 3.99 (t, J = 5.8 Hz, 2H), 3.82-3.77 (m, 8H), 2.82 (t, J = 6.8 Hz, 2H), 2.71 (t, J = 6.6 Hz, 2H), 2.10-1.85 (m, 4H), 1.32 (s, 9H), 1.18 (s, 9H);
13
C NMR (101 MHz, CDCl3) δ 157.4, 156.5, 153.6,
153.4, 134.1, 131.3, 131.0, 130.6, 126.0, 125.7, 113.7, 112.9, 111.7, 111.1, 101.4, 99.9, 74.4, 73.6, 55.6, 55.5, 47.4, 42.6, 30.33, 30.25, 29.9, 29.8, 28.0, 27.8, 27.34, 27.25, 23.6; HRMS (ESI+, m/z) calcd for (C17H22NO2)+ (M + H)+ 272.1646, found 272.1641.
General procedure for reaction conditions A. To a 6 dram vial containing alkyne (0.30 mmol), 4 mL of CH3CN and NaHCO3 (0.90 mmol, 76 mg) were added. To this solution I2 (0.60 mmol, 152 mg) dissolved in 2 mL CH3CN was added and the
S6
solution was allowed to stir for 24 hours. Reaction was quenched with H2O (10 mL) and Na2S2O7 was added to remove excess I2. This mixture was extracted with DCM (3 x 20 mL) and the resulting organic layer was dried over Na2SO4. After concentration under vacuum, the crude product was purified using column chromatography using hexanes/ethyl acetate as the eluent.
2-iodo-1-phenyl-6,7-dihydro-3H-pyrrolo[2,1-j]quinoline-3,9(5H)-dione (10). Product was isolated as a light yellow solid (110 mg, 91%): mp 229-230 oC; 1H NMR (400 MHz, CDCl3) δ 7.45-7.32 (m, 3H), 7.07 (dd, J = 8.1, 1.6 Hz, 2H), 6.54 (d, J = 9.8 Hz, 1H), 6.36 (t, J = 1.7 Hz, 1H), 6.20 (dd, J = 9.8, 1.7 Hz, 1H), 4.24 (dd, J = 14.2, 8.0 Hz, 1H), 2.93-2.79 (m, 1H), 2.63-2.41 (m, 2H), 2.15-2.02 (m, 1H), 1.97-1.80 (m, 1H);
13
C NMR (101 MHz, CDCl3) δ 184.5, 171.5, 159.9, 157.4, 145.6, 132.1,
131.6, 130.1, 129.5, 128.64, 128.62, 128.1, 128.0, 98.3, 74.2, 37.69, 27.1, 26.2; HRMS (ESI+, m/z) calcd for (C18H15INO2)+ (M + H)+ 404.0142, found 404.0126. 2-iodo-1-(p-tolyl)-6,7-dihydro-3H-pyrrolo[2,1-j]quinoline-3,9(5H)-dione
(11).
Product
was
isolated as a white solid (112 mg, 89%): mp 186-189; 1H NMR (400 MHz, CDCl3) δ 7.13 (d, J = 8.0 Hz, 2H), 6.96 (d, J = 8.1 Hz, 2H), 6.51 (d, J = 9.8 Hz, 1H), 6.35 (t, J = 1.6 Hz, 1H), 6.18 (dd, J = 9.8, 1.7 Hz, 1H), 4.22 (m, 1H), 2.87-2.78 (m, 1H), 2.53-2.43 (m, 2H), 2.33 (s, 3H), 2.10-2.00 (m, 1H), 1.91-1.79 (m, 1H); 13C NMR (101 MHz, CDCl3) δ 184.61, 171.6, 159.9, 157.6, 145.8, 140.4, 132.0, 129.43, 129.36, 128.7, 127.9, 98.0, 74.2, 37.7, 27.1, 26.2, 21.6; HRMS (ESI+, m/z) calcd for (C19H17INO2)+ (M + H)+ 418.0299, found 418.0283.
2-iodo-1-(4-methoxyphenyl)-6,7-dihydro-3H-pyrrolo[2,1-j]quinoline-3,9(5H)-dione (12). Product isolated as a beige solid (108 mg, 83%): mp 200-201; 1H NMR (400 MHz, CDCl3) δ 7.06 (d, J = 8.7 Hz, 2H), 6.84 (d, J = 8.7 Hz, 2H), 6.49 (d, J = 9.8 Hz, 1H), 6.36 (t, J = 1.6 Hz, 1H), 6.18 (dd, J = 9.8,
S7
1.7 Hz, 1H), 4.25-4.18 (m, 1H), 3.79 (s, 3H), 2.86-2.77 (m, 1H), 2.55-2.43 (m, 2H), 2.08-1.99 (m, 1H), 1.89-1.81 (m, 1H); 13C NMR (101 MHz, CDCl3) δ 184.6, 171.6, 160.9, 159.4, 157.7, 146.1, 131.9, 129.49, 129.46, 123.8, 114.1, 97.7, 74.2, 55.4, 37.7, 27.1, 26.2; HRMS (ESI+, m/z) calcd for (C20H20NO3)+ (M + H)+ 434.0248, found 434.0233.
2-iodo-1-(thiophen-3-yl)-6,7-dihydro-3H-pyrrolo[2,1-j]quinoline-3,9(5H)-dione (13). Product was isolated as a beige solid (94 mg, 76%): mp 218-221; 1H NMR (400 MHz, CDCl3) δ 7.53 (dd, J = 1.72, 3.04 Hz, 1H), 7.35-7.32 (m, 1H), 7.20 (dd, J = 5.1, 1.4 Hz, 1H), 6.50 (d, J = 9.8 Hz, 1H), 6.43 (t, J = 1.6 Hz, 1H), 6.26 (dd, J = 9.8, 1.7 Hz, 1H), 4.28-4.14 (m, 1H), 2.91-2.75 (m, 1H), 2.58-2.41 (m, 2H), 2.13-1.93 (m, 1H), 1.92-1.77 (m, 1H);
13
C NMR (101 MHz, CDCl3) δ 184.8, 171.7, 158.4, 153.9,
146.2, 131.9, 131.6, 129.6, 126.68, 126.65, 126.58, 96.8, 73.7, 37.6, 27.2, 26.2; HRMS (ESI+, m/z) calcd for (C16H13INO2S)+ (M + H)+ 409.9707, found 409.9693.
1-(cyclohex-1-en-1-yl)-2-iodo-6,7-dihydro-3H-pyrrolo[2,1-j]quinoline-3,9(5H)-dione (14). Product was isolated as a beige solid (81 mg, 66%): mp 171-172; 1H NMR (400 MHz, CDCl3) δ 6.47 (d, J = 9.7 Hz, 1H), 6.38-6.30 (m, 2H), 5.44-5.39 (m, 1H), 4.20-4.12 (m, 1H), 2.82-2.72 (m, 1H), 2.47-2.30 (m, 2H), 2.18-2.08 (m, 1H), 2.06-1.98 (m, 2H), 1.91-1.73 (m, 3H), 1.64-1.47 (m, 4H); 13C NMR (101 MHz, CDCl3) δ 185.0, 171.6, 162.3, 157.5, 145.5, 132.2, 132.0, 129.4, 128.8, 95.1, 74.6, 37.6, 27.7, 26.8, 26.0, 25.1, 22.3, 21.3; HRMS (ESI+, m/z) calcd for (C18H19INO2)+ (M + H)+ 408.0445, found 408.0435.
2-iodo-1-pentyl-6,7-dihydro-3H-pyrrolo[2,1-j]quinoline-3,9(5H)-dione (15). Product was isolated as a brown solid (54 mg, 45%): mp 74-77; 1H NMR (400 MHz, CDCl3) δ 6.46 (s, 2H), 6.36 (s, 1H), 4.18-4.11 (m, 1H), 2.81-2.72 (m, 1H), 2.47-2.28 (m, 2H), 2.19-1.93 (m, 1H), 1.87-1.73 (m, 1H), 1.46-
S8
1.32 (m, 2H), 1.29-1.19 (m, 4H), 0.85 (t, J = 8.0 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 184.9, 171.6, 161.6, 159.2, 146.0, 132.1, 128.4, 95.9, 73.9, 37.4, 31.8, 28.7, 27.7, 27.2, 26.1, 22.0, 13.8; HRMS (ESI+, m/z) calcd for (C17H21INO2)+ (M + H)+ 398.0612, found 398.0598.
General procedure for the preparation of 19 and 20. To a 6 dram vial containing a stir bar, compound 10 (55 mg, 0.14 mmol) and 3 mL of DMF were added. After 10 had been fully dissolved, boronic acid (0.2 mmol) and Na2CO3 (43.56 mg, 0.41 mmol) were added along with 0.75 mL of water. After the addition of Pd(PPh3)4 (15.8 mg, 0.0137 mmol), the reaction vial was sealed and flushed with N2. The reaction was monitored by TLC and showed completion after 24 h. The DMF was removed via rotary evaporation and the crude product was dissolved in DCM (30 mL). The resulting organic mixture was washed with water (3 x 5 mL), dried over Na2SO4 and concentrated under vacuum. Pure product was obtained by column chromatography using hexanes/ethyl acetate as the eluent.
1,2-diphenyl-6,7-dihydro-3H-pyrrolo9[2,1-j]quinoline-3,9(5H)-dione (19). Product was isolated as a reddish-brown solid (42 mg, 84%): mp 174-177; 1H NMR (400 MHz, CDCl3) δ 7.43-7.37 (m, 2H), 7.35-7.22 (m, 6H), 6.98 (dd, J = 6.9, 1.3 Hz, 2H), 6.63 (d, J = 9.8 Hz, 1H), 6.42 (d, J = 1.6 Hz, 1H), 6.20 (dt, J = 9.8, 1.5 Hz, 1H), 4.35-4.26 (m, 1H), 2.92-2.82 (m, 1H), 2.62-2.48 (m, 1H), 2.26-2.15 (m, 1H), 1.97-1.84 (m, 1H); 13C NMR (101 MHz, CDCl3) δ 184.9, 174.0, 159.2, 151.5, 147.2, 135.8, 132.1, 131.5, 130.5, 129.5, 129.44, 129.39, 128.9, 128.8, 128.7, 128.3, 71.3, 37.0, 27.3, 26.5; HRMS (ESI+, m/z) calcd for (C24H20NO2)+ (M + H)+ 354.1489, found 354.1479.
Synthesis of 1-phenyl-2-(thiophene-3-yl)-6,7-dihydro-3h-pyrrolo[2,1-j]quinoline-3,9(5H) –dione (20). Product was isolated as a brown solid (45 mg, 89%): mp 177-179. 1H NMR (400 MHz, CDCl3) δ
S9
8.08 (dd, J = 3.0, 1.3 Hz, 1H), 7.41-7.30 (m, 3H), 7.10 (dd, J = 5.1, 3.1 Hz, 1H), 6.98 (dd, J = 8.1, 1.6 Hz, 2H), 6.77 (dd, J = 5.2, 1.3 Hz, 1H), 6.62 (d, J = 9.8 Hz, 1H), 6.30 (t, J = 1.6 Hz, 1H), 6.21 (dd, J = 9.7, 1.7 Hz, 1H), 4.34-4.25 (m, 1H), 2.92-2.81 (m, 1H), 2.60-2.41 (m, 2H), 2.21-2.11 (m, 1H), 1.951.81 (m, 1H); 13C NMR (101 MHz, CDCl3) δ 184.8, 173.9, 159.1, 148.8, 146.9, 132.2, 131.6, 131.1, 130.2, 129.5, 129.0, 128.9, 128.8, 127.2, 127.1, 125.0, 77.5, 77.2, 76.8, 71.3, 37.0, 27.1, 26.3; HRMS (ESI+, m/z) calcd for (C22H18NO2S)+ (M + H)+ 360.1053, found 360.1040.
S10
1. 1-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)-3-phenylprop-2-yn-1-one (2)
S11
1-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)-3-phenylprop-2-yn-1-one (2)
S12
S13
1-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)oct-2-yn-1-one (3)
S14
1-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)oct-2-yn-1-one (3)
S15
6-methoxy-3,4-dihydroquinoline-1(2H)-carbonyl chloride (4)
S16
6-methoxy-3,4-dihydroquinoline-1(2H)-carbonyl chloride (4)
S17
1-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)-3-(p-tolyl)prop-2-yn-1-one (5)
S18
1-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)-3-(p-tolyl)prop-2-yn-1-one (5)
S19
1-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)-3-(4-methoxyphenyl)prop-2-yn-1-one (6)
S20
1-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)-3-(4-methoxyphenyl)prop-2-yn-1-one (6)
S21
1-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)-3-(thiophen-3-yl)prop-2-yn-1-one (7)
S22
1-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)-3-(thiophen-3-yl)prop-2-yn-1-one (7)
S23
3-(cyclohex-1-en-1-yl)-1-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)prop-2-yn-1-one (8)
S24
3-(cyclohex-1-en-1-yl)-1-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)prop-2-yn-1-one (8)
S25
1-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)-4,4-dimethylpent-2-yn-1-one (9)
S26
1-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)-4,4-dimethylpent-2-yn-1-one (9)
S27
2-iodo-1-phenyl-6,7-dihydro-3H-pyrrolo[2,1-j]quinoline-3,9(5H)-dione (10)
S28
2-iodo-1-phenyl-6,7-dihydro-3H-pyrrolo[2,1-j]quinoline-3,9(5H)-dione (10)
S29
2-iodo-1-(p-tolyl)-6,7-dihydro-3H-pyrrolo[2,1-j]quinoline-3,9(5H)-dione (11)
S30
2-iodo-1-(p-tolyl)-6,7-dihydro-3H-pyrrolo[2,1-j]quinoline-3,9(5H)-dione (11)
S31
2-iodo-1-(4-methoxyphenyl)-6,7-dihydro-3H-pyrrolo[2,1-j]quinoline-3,9(5H)-dione (12)
S32
2-iodo-1-(4-methoxyphenyl)-6,7-dihydro-3H-pyrrolo[2,1-j]quinoline-3,9(5H)-dione (12)
S33
2-iodo-1-(thiophen-3-yl)-6,7-dihydro-3H-pyrrolo[2,1-j]quinoline-3,9(5H)-dione (13)
S34
2-iodo-1-(thiophen-3-yl)-6,7-dihydro-3H-pyrrolo[2,1-j]quinoline-3,9(5H)-dione (13)
S35
1-(cyclohex-1-en-1-yl)-2-iodo-6,7-dihydro-3H-pyrrolo[2,1-j]quinoline-3,9(5H)-dione (14)
S36
1-(cyclohex-1-en-1-yl)-2-iodo-6,7-dihydro-3H-pyrrolo[2,1-j]quinoline-3,9(5H)-dione (14)
S37
2-iodo-1-pentyl-6,7-dihydro-3H-pyrrolo[2,1-j]quinoline-3,9(5H)-dione (15)
S38
2-iodo-1-pentyl-6,7-dihydro-3H-pyrrolo[2,1-j]quinoline-3,9(5H)-dione (15)
S39
1,2-diphenyl-6,7-dihydro-3H-pyrrolo9[2,1-j]quinoline-3,9(5H)-dione (19)
S40
1,2-diphenyl-6,7-dihydro-3H-pyrrolo9[2,1-j]quinoline-3,9(5H)-dione (19)
S41
2-(3-methoxyphenyl)-1-phenyl-6,7-dihydro-3H-pyrrolo[2,1-j]quinline-3,9(5H)-dione (20)
S42
2-(3-methoxyphenyl)-1-phenyl-6,7-dihydro-3H-pyrrolo[2,1-j]quinline-3,9(5H)-dione (20)
S43
Synthesis of 1-phenyl-2-(thiophene-3-yl)-6,7-dihydro-3h-pyrrolo[2,1-j]quinoline-3,9(5H) –dione (21)
S44
Synthesis of 1-phenyl-2-(thiophene-3-yl)-6,7-dihydro-3h-pyrrolo[2,1-j]quinoline-3,9(5H) –dione (21)
S45
