2-cyclopentyloxyaniline

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Cyclopentoxyaniline (10.0 g, 0.057 mole), N-methylolpyrrolidone (9.75 g, 0.85 mole) and xylene (25 cc) were refluxed under azeotropic conditions with the removal of 1.5 cc of water. The xylene was removed by rotary evaporation and the product was crystallized from 100 cc of hexane to yield 8.0 g (51.6%) of product, m.p. 87°-87.5° C. The xylene was removed by rotary evaporation the product was crystallized from 100 cc of hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Cyclopentoxyaniline (10.0 g, 0.057 mole), N-methylolpyrrolidone (9.75 g, 0.85 mole) and xylene (25 cc) were refluxed under azeotropic conditions with the removal of 1.5 cc of water. The xylene was removed by rotary evaporation and the product was crystallized from 100 cc of hexane to yield 8.0 g (51.6%) of product, m.p. 87°-87.5° C. The xylene was removed by rotary evaporation the product was crystallized from 100 cc of hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Iron 60 mesh (51.9 g, 0.93 mole), water (220 cc), ethanol (244 cc) and concentrated hydrochloric acid (14.2 cc) were heated to reflux under a nitrogen blanket. Then 2-cyclopentoxynitrobenzene (55.2 g, 0.27 mole) was added at reflux over a period of 2 hrs. The reaction was maintained at reflux for an additional 3 hrs. The pH was adjusted to 7-8 by the addition of concentrated ammonium hydroxide. The reaction mixture then was filtered at 30° C., and the filtrate was washed with 200 cc of ether. The filtrate was extracted with 4×50 cc of ether and the combined ether extracts were subjected to rotary evaporation. The crude product was fractionally distilled at 126°-130° C. at 2.0-2.5 mm. Hg to yield 30.3 g (64.3%) of product. to reflux under a nitrogen blanket at reflux over a period of 2 hrs The reaction was maintained at reflux for an additional 3 hrs The reaction mixture then was filtered at 30° C. the filtrate was washed with 200 cc of ether The filtrate was extracted with 4×50 cc of ether the combined ether extracts were subjected to rotary evaporation The crude product was fractionally distilled at 126°-130° C. at 2.0-2.5 mm. Hg

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Iron 60 mesh (51.9 g, 0.93 mole), water (220 cc), ethanol (244 cc) and concentrated hydrochloric acid (14.2 cc) were heated to reflux under a nitrogen blanket. Then 2-cyclopentoxynitrobenzene (55.2 g, 0.27 mole) was added at reflux over a period of 2 hrs. The reaction was maintained at reflux for an additional 3 hrs. The pH was adjusted to 7-8 by the addition of concentrated ammonium hydroxide. The reaction mixture then was filtered at 30° C., and the filtrate was washed with 200 cc of ether. The filtrate was extracted with 4×50 cc of ether and the combined ether extracts were subjected to rotary evaporation. The crude product was fractionally distilled at 126°-130° C. at 2.0-2.5 mm. Hg to yield 30.3 g (64.3%) of product. to reflux under a nitrogen blanket at reflux over a period of 2 hrs The reaction was maintained at reflux for an additional 3 hrs The reaction mixture then was filtered at 30° C. the filtrate was washed with 200 cc of ether The filtrate was extracted with 4×50 cc of ether the combined ether extracts were subjected to rotary evaporation The crude product was fractionally distilled at 126°-130° C. at 2.0-2.5 mm. Hg

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-(Cyclopentyloxy)-1-nitrobenzene (1.04 g, 80%) was prepared from cyclopentanol (0.46 ml, 5.0 mmol) and 1-fluoro-2-nitrobenzene (0.71 g, 5.0 mmol) following the general procedure G. This was reduced to 2-(cyclopentyloxy)aniline (0.30 g, 68%, 2.5 mmol scale) following general procedure B. N-(2-Cyclopentyloxyphenyl)-N′-(thiazol-2-yl)urea (212 mg, 70%) was prepared from 2-(cyclopentyloxy)aniline (177 mg, 1.0 mmol) and 2-aminothiazole (100 mg, 1.0 mmol) following the general procedure D.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-(Cyclopentyloxy)-1-nitrobenzene (1.04 g, 80%) was prepared from cyclopentanol (0.46 ml, 5.0 mmol) and 1-fluoro-2-nitrobenzene (0.71 g, 5.0 mmol) following the general procedure G. This was reduced to 2-(cyclopentyloxy)aniline (0.30 g, 68%, 2.5 mmol scale) following general procedure B. N-(2-Cyclopentyloxyphenyl)-N′-(thiazol-2-yl)urea (212 mg, 70%) was prepared from 2-(cyclopentyloxy)aniline (177 mg, 1.0 mmol) and 2-aminothiazole (100 mg, 1.0 mmol) following the general procedure D.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared by the coupling ethyl (2E)-(6-chlorospiro[chromene-2,1′-cyclobutan]-4(3H)-ylidene)acetate (Step 2 of Intermediate 1) with 2-(cyclopentyloxy)aniline (120 mg, 0.681 mmol) (150 mg, 0.565 mmol) in presence of EDCI.HCl (163 mg, 0.851 mmol), HOBt (130 mg, 0.851 mmol) and triethylamine (157 μl, 1.134 mmol) in dichloromethane (5 ml) as described in Method A to give 95 mg of the product as a white solid; 1H NMR (300 MHz, CDCl3) δ 1.53-1.65 (m, 8H), 1.74-1.90 (m, 4H), 2.22-2.30 (m, 2H), 2.47-2.57 (m, 2H), 3.50 (s, 2H), 4.67 (br s, 1H), 6.75 (d, J=8.1 Hz, 2H), 6.85-6.96 (m, 2H), 7.04-7.10 (m, 2H), 8.32 (d, J=7.8 Hz, 1H).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Cyclopentoxyaniline (10.0 g, 0.057 mole), N-methylolpyrrolidone (9.75 g, 0.85 mole) and xylene (25 cc) were refluxed under azeotropic conditions with the removal of 1.5 cc of water. The xylene was removed by rotary evaporation and the product was crystallized from 100 cc of hexane to yield 8.0 g (51.6%) of product, m.p. 87°-87.5° C. The xylene was removed by rotary evaporation the product was crystallized from 100 cc of hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Iron 60 mesh (51.9 g, 0.93 mole), water (220 cc), ethanol (244 cc) and concentrated hydrochloric acid (14.2 cc) were heated to reflux under a nitrogen blanket. Then 2-cyclopentoxynitrobenzene (55.2 g, 0.27 mole) was added at reflux over a period of 2 hrs. The reaction was maintained at reflux for an additional 3 hrs. The pH was adjusted to 7-8 by the addition of concentrated ammonium hydroxide. The reaction mixture then was filtered at 30° C., and the filtrate was washed with 200 cc of ether. The filtrate was extracted with 4×50 cc of ether and the combined ether extracts were subjected to rotary evaporation. The crude product was fractionally distilled at 126°-130° C. at 2.0-2.5 mm. Hg to yield 30.3 g (64.3%) of product. to reflux under a nitrogen blanket at reflux over a period of 2 hrs The reaction was maintained at reflux for an additional 3 hrs The reaction mixture then was filtered at 30° C. the filtrate was washed with 200 cc of ether The filtrate was extracted with 4×50 cc of ether the combined ether extracts were subjected to rotary evaporation The crude product was fractionally distilled at 126°-130° C. at 2.0-2.5 mm. Hg

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-(Cyclopentyloxy)-1-nitrobenzene (1.04 g, 80%) was prepared from cyclopentanol (0.46 ml, 5.0 mmol) and 1-fluoro-2-nitrobenzene (0.71 g, 5.0 mmol) following the general procedure G. This was reduced to 2-(cyclopentyloxy)aniline (0.30 g, 68%, 2.5 mmol scale) following general procedure B. N-(2-Cyclopentyloxyphenyl)-N′-(thiazol-2-yl)urea (212 mg, 70%) was prepared from 2-(cyclopentyloxy)aniline (177 mg, 1.0 mmol) and 2-aminothiazole (100 mg, 1.0 mmol) following the general procedure D.