3,4-Dichloro-6-fluoroaniline

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3,4-Dichloro-6-fluoroaniline (1 equivalent) was reacted with 4-chloro-6-nitroquinazoline (3.5 equivalents), in iso-propylalcohol. After filtration, 4-[(3,4-dichloro-6-fluorophenyl)amino]-6-nitroquinazoline (compound 1) was obtained in 78% yield. After filtration

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In one particular, 3,4-dichloro-6-fluoroaniline is reacted with 4-chloro-6-nitroquinazoline, so as to produce 4-[(3,4-dichloro-6-fluorophenyl)amino]-6-nitroquinazoline, which is reduced, by means of an ethanolic solution of hydrazine hydrate and Raney®Nickel, so as to produce 4-[(3,4-dichloro-6-fluorophenyl)amino]-6-aminoquinazoline. Then, the 4-[(3,4-dichloro-6-fluorophenyl)amino]-6-aminoquinazoline is reacted with a carbon-11 labeled acryloyl chloride so as to produce a carbon-11 labeled {4-[(3,4-dichloro-6-fluorophenyl)amino]quinazoline-6-yl]acrylamide (radiolabeled Compound 3).

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3,4-Dichloro-6-fluoroaniline (1 equivalent) was reacted with 4-chloro-7-fluoro-6-nitroquinazoline (3.5 equivalents), in iso-propylalcohol. After filtration, 4-[(3,4-dichloro-6-fluorophenyl)amino]-7-fluoro-6-nitroquinazoline was obtained in 78% yield. After filtration

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3,4-Dichloro-6-fluoroaniline (1 equivalent, prepared as described in U.S. Pat. No. 6,126,917) was reacted with 4-chloro-6-nitroquinazoline (3.5 equivalents, prepared by reacting 6-nitroquinazoline with thionyl chloride, according to known procedures), in iso-propylalcohol. After filtration, 4-[(3,4-dichloro-6-fluorophenyl)amino]-6-nitroquinazoline (compound 1) was obtained in 60% yield. m.p.=270–271° C.; MS (m/z): 353.2, 355.2 (M+); 1H-NMR: δ=6.97 (d, 1H), 7.345 (d, 1H), 7.885 (d, 1H), 8.405 (d, 1H), 8.554 (dd, 1H), 8.8 (d, 1H) ppm. HPLC conditions: C-18 column, 55% acetate buffer, PH=3.8/45% acetonitrile, flow=1 ml/min; r.t.=7.15 minutes. After filtration

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In one particular, 3,4-dichloro-6-fluoroaniline is reacted with 4-chloro-6-nitroquinazoline, so as to produce 4-[(3,4-dichloro-6-fluorophenyl)amino]-6-nitroquinazoline, which is reduced, by means of an ethanolic solution of hydrazine hydrate and Raney®Nickel, so as to produce 4-[(3,4-dichloro-6-fluorophenyl)amino]-6-aminoquinazoline. Then, the 4-[(3,4-dichloro-6-fluorophenyl)amino]-6-aminoquinazoline is reacted with 4-bromocrotonyl chloride, so as to produce 4-bromo-N-{4-[(3,4-dichloro-6-fluorophenyl)amino]quinazoline-6-yl}-2-butenamide, which is then reacted with methylamine, so as to produce N-{4-[(3,4-dichloro-6-fluorophenyl)amino]quinazoline-6-yl}-4-(methylamino)-2-butenamide. The obtained methylamino derivative of the butenamide is reacted with a carbon-11 labeled methyliodide, so as to produce a carbon-11 labeled N-{4-[(3,4-dichloro-6-fluorophenyl)amino]quinazoline-6-yl}-4-(dimethylamino)-2-butenamide (carbon-11 labeled Compound 4).

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In another particular, which includes a quinazoline that is substituted by two different reactive groups at positions 6 and 7 thereof, 3,4-dichloro-6-fluoroaniline is reacted with 4-chloro-7-fluoro-6-nitroquinazoline, so as to produce 4-[(3,4-dichloro-6-fluorophenyl)amino]-7-fluoro-6-nitroquinazoline. The 4-[(3,4-dichloro-6-fluorophenyl)amino]-7-fluoro-6-nitroquinazoline is then reacted with a sodium salt of 3-(4-morpholinyl-1-propanol), so as to produce 4-[(3,4-dichloro-6-fluoro-phenyl)amino]-7-[3-(4-morpholinyl)propoxy]-6-nitroquinazoline, which is reduced, by means of an ethanolic solution of hydrazine hydrate and Raney®Nickel, so as to produce 6-amino-4-[(3,4-dichloro-6-fluorophenyl)amino]-7-[3-(4-morpholinyl)propoxy]quinazoline. The product is then reacted with a carbon-11 labeled acryloyl chloride so as to produce a carbon-11 labeled N-{4-[(3,4-dichloro-6-fluorophenyl)amino]-7-[3-(4-morpholinyl)propoxy]quinazoline-6-yl}acrylamide (carbon-11 labeled morpholino-substituted Compound 3).

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In one particular, which includes a quinazoline that is substituted by one reactive group at position 6 thereof, 3,4-dichloro-6-fluoroaniline is reacted with 4-chloro-6-nitroquinazoline, so as to produce 4-[(3,4-dichloro-6-fluorophenyl)amino]-6-nitroquinazoline, which is reduced, by means of an ethanolic solution of hydrazine hydrate and Raney®Nickel, so as to produce 4-[(3,4-dichloro-6-fluorophenyl)amino]-6-aminoquinazoline. Then, the 4-[(3,4-dichloro-6-fluorophenyl)amino]-6-aminoquinazoline is reacted with a carbon-11 labeled acryloyl chloride so as to produce a carbon-11 labeled N-{4-[(3,4-dichloro-6-fluorophenyl)amino]quinazoline-6-yl}acrylamide (carbon-11 labeled Compound 3).

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Tin (II) chloride dehydrate (27.0 g, 119.6 mmol) was dissolved in ethanol and 1,2-dichloro-4-fluoro-5-nitrobenzene (5.0 g, 23.8 mmol) was added dropwise. Temperature rose to near reflux during the addition and was complete upon cooling. The reaction mixture was carefully added to saturated aqueous sodium bicarbonate and then extracted with ethyl acetate. The organic phase was washed several more times with water, dried, filtered and concentrated to give the title compound as a yellow solid: 1H NMR (CDCl3): δ 7.17 (d, 1H), 6.84 (d, 1H), 3.78 (br s, 2H). to near reflux during the addition upon cooling extracted with ethyl acetate The organic phase was washed several more times with water dried filtered concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Tin (II) chloride dehydrate (27.0 g, 119.6 mmol) was dissolved in ethanol and 1,2-dichloro-4-fluoro-5-nitrobenzene (5.0 g, 23.8 mmol) was added dropwise. Temperature rose to near reflux during the addition and was complete upon cooling. The reaction mixture was carefully added to saturated aqueous sodium bicarbonate and then extracted with ethyl acetate. The organic phase was washed several more times with water, dried, filtered and concentrated to give the title compound as a yellow solid: 1H NMR (CDCl3): δ 7.17 (d, 1H), 6.84 (d, 1H), 3.78 (br s, 2H). to near reflux during the addition upon cooling extracted with ethyl acetate The organic phase was washed several more times with water dried filtered concentrated