2-CHLORO-4,8-DIMETHYLQUINOLINE

To chloroquinoline 5 (775 mg, 4.0 mmol) in 1, 4-dioxane (12 mL) was added 3-phenyl-2-propyn-1-ol (1.0 mL, 8.0mmol). Potassium tert-butoxide (673mg, 6.0 mmol) was added, and the flask was rinsed with 1, 4-dioxane (6 mL). The reaction was equipped with an air condenser and heated to 98 C open to air for 18 hours. After cooling to room temperature, ethyl acetate (15 mL) and H2O (15 mL) were added. The layers were separated and the aqueous layer was extracted with ethyl acetate (15 mL x 2). The combined organic layers were washed with 1:1 brine/H2O (15 mL) and brine (15 mL) and dried (MgSO4). After filtration, the reaction mixture was concentrated in vacuo. Purification by column chromatography (SiO2, 19:1 hexanes/ethyl acetate) provided 995 mg (86% yield) of 6cas a white solid. mp: 58-60 C; 1H NMR (400 MHz, CDCl3):d7.72 (d, J = 8.4 Hz, 1H), 7.42-7.48 (m, 3H), 7.23-7.32 (m, 4H), 6.81 (s, 1H), 5.34 (s, 2H), 2.71 (s, 3H), 2.61 (s, 3H; 13C NMR (100MHz, CDCl3): d159.4, 147.4, 145.0, 135.9, 131.9, 129.6, 128.4, 128.2, 125.3, 123.5, 122.7, 121.4, 112.2, 105.0, 85.8, 84.9, 53.9, 19.0, 18.1; IR (neat): 3061, 2922, 2243, 1610, 1583, 1448, 1323 cm-1; HRMS (ESI)m/z 310.1217 [310.1208 calcd for C20H17NONa (M+Na)+].To chloroquinoline 5 (775mg, 4.0mmol) in 1, 4-dioxane (12 mL) was added 2-butyn-1-ol (0.60 mL, 8.0 mmol). Potassium tert-butoxide (673mg, 6.0mmol) was added, and the flask was rinsed with 1, 4-dioxane (6 mL). The reaction was equipped with an air condenser and heated to 98 C open to air for 18 hours. After cooling to room temperature, ethyl acetate (15 mL) and H2O (15 mL) were added. The layers were separated and the aqueous layer was extracted with ethyl acetate (15 mL x 2). The combined organic layers were washed with 1:1 brine/H2O (15 mL) and brine (15 mL) and dried (MgSO4). After filtration, the reaction mixture was concentrated in vacuo. Purification by column chromatography (SiO2, 19:1hexanes/ethyl acetate) provided 882 mg (97% yield) of 6b as a white solid. mp: 68-70 C; 1H NMR (400 MHz, CDCl3):d7.70 (d, J = 8.0 Hz, 1H), 7.45 (d, J = 7.2Hz, 1H), 7.27 (t, J = 7.6 Hz, 1H), 6.78 (s, 1H), 5.07 (d, J = 4.0 Hz, 2H), 2.67 (s, 3H), 2.59(s, 3H), 1.87 (t, J = 2.4Hz, 3H); 13C NMR (100 MHz, CDCl3): d159.5, 147.2, 145.0, 135.8, 129.5, 125.2, 123.4, 121.4, 112.2, 82.3, 74.7, 53.8, 19.0, 18.1, 3.7; IR (neat): 3026, 2922, 2241, 1612, 1582, 1326 cm-1; HRMS (ESI) m/z 226.1230 [226.1232 calcd for C15H16NO(M+H)+].To chloroquinoline 5 (1.55 g, 8.0 mmol) in 1, 4-dioxane (24 mL) was added 2-octyn-1-ol (2.29 mL, 16.0 mmol). Potassium tert-butoxide (1.35 g, 12.0mmol) was added, and the flask was rinsed with 1, 4-dioxane (12 mL). The reaction was equipped with an air condenser and heated to 98 C open to air for 18 hours. After cooling to room temperature, ethyl acetate (30 mL) and H2O(30 mL) were added. The layers were separated and the aqueous layer was extracted with ethyl acetate (30 mL x 2). The combined organic layers were washed with 1:1 brine/H2O (30 mL) and brine (30 mL) and dried (MgSO4). After filtration, the reaction mixture was concentrated in vacuo. Purification by column chromatography (SiO2, 19:1hexanes/ethyl acetate) provided 2.30 g (99% yield) of 6a as a colorless oil. 1H NMR (400 MHz, CDCl3):d7.70 (d, J = 8.0 Hz, 1H), 7.46 (d, J = 7.6Hz, 1H), 7.27 (t, J = 7.6 Hz, 1H), 6.79 (s, 1H), 5.12 (s, 2H), 2.68 (s, 3H), 2.59 (s, 3H), 2.24 (app t, J = 7.2 Hz, 2H), 1.53 (pentet, J =6.8 Hz, 2H), 1.23-1.41 (m 4H), 0.87 (t, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3): d159.6, 147.1, 145.0, 135.8, 129.5, 125.2, 123.4, 121.4, 112.3, 86.9, 75.5, 53.9, 31.0, 28.3, 22.2, 19.0, 18.9, 18.1, 13.9; IR (neat): 3026, 2930, 2863, 2237, 1612, 1582, 1450, 1326 cm-1; HRMS (ESI) m/z 304.1674 [304.1677calcd for C19H23NONa (M+Na)+].

Molecular Weight:191.65
XLogP3:3.9
Hydrogen Bond Acceptor Count:1
Exact Mass:191.0501770
Monoisotopic Mass:191.0501770
Topological Polar Surface Area:12.9
Heavy Atom Count:13
Complexity:183
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes