2-chlorofuran

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

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

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Phosphorus pentachloride (40.53 g, 0.1947 mol) was added portionwise (caution, foaming) over 5 min at 25° C. to chlorosulfonic acid (56.8 g, 32.4 mL, 0.487 mol) and the resulting solution was stirred at 25° C. for 10 min. Then, 2-chlorofuran (20.0 g, 0.1947 mol) was added in one portion and the resulting dark suspension was heated to 55° C. for 1.0 h during which time foaming occurred and subsided. The reaction mixture was then poured onto ice and the resulting suspension was extracted with CH2Cl2 (250 mL). The organic was filtered through a pad of celite, washed with brine (70 mL) and dried over MgSO4. The solvent was removed in vacuo to provide 5-chlorofuran-2-sulfonyl chloride as a black oil (14.1 g, 36.02%). 1H-NMR (DMSO-d6, 400 MHz) δ7.05 (d, 1H); 6.35 (d, 1H). the resulting dark suspension was heated to 55° C. for 1.0 h during which time The reaction mixture was then poured onto ice the resulting suspension was extracted with CH2Cl2 (250 mL) The organic was filtered through a pad of celite washed with brine (70 mL) dried over MgSO4 The solvent was removed in vacuo

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Phosphorus pentachloride (40.53 g, 0.1947 mol) was added portionwise (caution, foaming) over 5 min at 25° C. to chlorosulfonic acid (56.8 g, 32.4 mL, 0.487 mol) and the resulting solution was stirred at 25° C. for 10 min. Then, 2-chlorofuran (20.0 g, 20 0.1947 mol) was added in one portion and the resulting dark suspension was heated to 55° C. for 1.0 h during which time foaming occurred and subsided. The reaction mixture was then poured onto ice and the resulting suspension was extracted with CH2Cl2 (250 mL). The organic was filtered through a pad of celite, washed with brine (70 mL) and dried over MgSO4. The solvent was removed in vacuo to provide 5-chlorofuran-2-sulfonyl chloride as a black oil (14.1 g, 36.02%). 1H-NMR (DMSO-d6, 400 MHz) δ 7.05 (d, 1H); 6.35 (d, 1 H). the resulting dark suspension was heated to 55° C. for 1.0 h during which time The reaction mixture was then poured onto ice the resulting suspension was extracted with CH2Cl2 (250 mL) The organic was filtered through a pad of celite washed with brine (70 mL) dried over MgSO4 The solvent was removed in vacuo

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Phosphorus pentachloride (40.53 g, 0.1947 mol) was added portionwise (caution, foaming) over 5 min at 25° C. to chlorosulfonic acid (56.8 g, 32.4 mL, 0.487 mol) and the resulting solution was stirred at 25° C. for 10 min. Then, 2-chlorofuran (20.0 g, 0.1947 mol) was added in one portion and the resulting dark suspension was heated to 55° C. for 1.0 h during which time foaming occurred and subsided. The reaction mixture was then poured onto ice and the resulting suspension was extracted with CH2Cl2 (250 mL). The organic was filtered through a pad of celite, washed with brine (70 mL) and dried over MgSO4. The solvent was removed in vacuo to provide 5-chlorofuran-2-sulfonyl chloride as a black oil (14.1 g, 36.02%). 1H-NMR (DMSO-d6, 400 MHz) δ7.05 (d, 1H); 6.35 (d, 1H). the resulting dark suspension was heated to 55° C. for 1.0 h during which time The reaction mixture was then poured onto ice the resulting suspension was extracted with CH2Cl2 (250 mL) The organic was filtered through a pad of celite washed with brine (70 mL) dried over MgSO4 The solvent was removed in vacuo

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Phosphorus pentachloride (40.53 g, 0.1947 mol) was added portionwise (caution, foaming) over 5 min at 25° C. to chlorosulfonic acid (56.8 g, 32.4 mL, 0.487 mol) and the resulting solution was stirred at 25° C. for 10 min. Then, 2-chlorofuran (20.0 g, 0.1947 mol) was added in one portion and the resulting dark suspension was heated to 55° C. for 1.0 h during which time foaming occurred and subsided. The reaction mixture was then poured onto ice and the resulting suspension was extracted with CH2Cl2 (250 mL). The organic was filtered through a pad of celite, washed with brine (70 mL) and dried over MgSO4. The solvent was removed in vacuo to provide 5-chlorofuran-2-sulfonyl chloride as a black oil (14.1 g, 36.02%). 1H-NMR (DMSO-d6, 400 MHz) δ7.05 (d, 1H); 6.35 (d, 1H). the resulting dark suspension was heated to 55° C. for 1.0 h during which time The reaction mixture was then poured onto ice the resulting suspension was extracted with CH2Cl2 (250 mL) The organic was filtered through a pad of celite washed with brine (70 mL) dried over MgSO4 The solvent was removed in vacuo

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

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

Procedure: To a solution of 50 mg of 1-(4-{4-[3-(4-Amino-phenylamino)-[1,2,4]triazol-1-yl]-pyridin-2-yl}-2,6-dimethyl-piperazin-1-yl)-ethanone (0.123 mMol. 1.00 equiv) in 2 mL of NMP was added 5 mL of CH2Cl2 and 500 μL of Hunig's base followed by 100 μL of 2-furanyl chloride (1.01 mMol, 8.13 equiv). The reaction mixture was stirred for 1 hr and concentrated. The resulting oil was purified via flash chromatography (EtOAc) to yield 1.4 mg of Furan-2-carboxylic acid (4-{1-[2-(4-acetyl-3,5-dimethyl-piperazin-1-yl)-pyridin-4-yl]-1H-[1,2,4]triazol-3-ylamino}-phenyl)-amide (0.0028 mMol, 2.3% yield). 1H NMR (500 MHz, MeOD-d4) ∂ 8.95 (1H, s), 8.18 (1H, d), 7.72 (1H, m), 7.61 (4H, m), 7.25 (2H, m), 7.15 (1H, m), 6.61 (1H, s), 4.30 (2H, m), 3.30 (2H, m), 3.15 (2H, m), 2.20 (3H, s), 1.35 (6H, m) ppm. LC/MS: 2.2 min/501.3 (M+1). concentrated The resulting oil was purified via flash chromatography (EtOAc)

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Phosphorus pentachloride (40.53 g, 0.1947 mol) was added portionwise (caution, foaming) over 5 min at 25° C. to chlorosulfonic acid (56.8 g, 32.4 mL, 0.487 mol) and the resulting solution was stirred at 25° C. for 10 min. Then, 2-chlorofuran (20.0 g, 0.1947 mol) was added in one portion and the resulting dark suspension was heated to 55° C. for 1.0 h during which time foaming occurred and subsided. The reaction mixture was then poured onto ice and the resulting suspension was extracted with CH2Cl2 (250 mL). The organic was filtered through a pad of celite, washed with brine (70 mL) and dried over MgSO4. The solvent was removed in vacuo to provide 5-chlorofuran-2-sulfonyl chloride as a black oil (141 g, 36.02%). 1H-NMR (DMSO-d6, 400 MHz) δ 7.05 (d, 1H); 6.35 (d, 1H). the resulting dark suspension was heated to 55° C. for 1.0 h during which time The reaction mixture was then poured onto ice the resulting suspension was extracted with CH2Cl2 (250 mL) The organic was filtered through a pad of celite washed with brine (70 mL) dried over MgSO4 The solvent was removed in vacuo

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

Procedure: To a solution of 4-{1-perhydro-2H-pyran-2-yl-5-[1-(triphenylmethyl)(1,2,4-triazol-3-yl)]1H-indazol-3-yl}phenylamine (0.300 g, 0.498 mmol) was added tetrahydrofuran (4.50 mL), triethylamine (0.345 mL, 2.48 mmol), and 2-furyl chloride (0.058 mL, 0.735 mmol). The mixture was stirred for 16 h at ambient temperature and poured into saturated sodium bicarbonate (50 mL). The aqueous layer was extracted with ethyl acetate. The combined organic extracts were washed with saturated sodium bicarbonate, dried over anhydrous sodium sulfate, filtered and evaporated. Purification by preparative HPLC (30–80% acetonitrile/water) followed by washing with saturated sodium bicarbonate and extraction with ethyl acetate gave the title compound (0.0086 g, 5% yield). 1H NMR (DMSO-d6) δ 8.75 (d, 1H), 8.10 (m, 6H), 7.74 (m, 1H), 7.39 (d, 1H), 6.75 (m, 1H). ES-MS (m/z) 371 [M+1]+ The aqueous layer was extracted with ethyl acetate The combined organic extracts were washed with saturated sodium bicarbonate dried over anhydrous sodium sulfate filtered evaporated Purification by preparative HPLC (30–80% acetonitrile/water) by washing with saturated sodium bicarbonate and extraction with ethyl acetate

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

Procedure: To a solution of 3-(3-aminophenyl)-1-perhydro-2H-pyran-2-yl-1H-indazole-5-carbonitrile (0.300 g, 0.94 mmol) in tetrahydrofuran (10 mL), was added 2-furyl chloride (0.139 mL, 1.41 mmol) and triethyl amine (0.655 mL, 4.7 mmol). After stirring at room temperature overnight, the reaction mixture was concentrated under reduced pressure and the residue was partitioned between ethyl acetate and water. The organic phase was dried under vacuum and the title product was purified by column chromatography (SiO2, 20–30% ethyl acetate in hexanes) (0.370 g, 95%): ES-MS (m/z) 413 [M+H]+. the reaction mixture was concentrated under reduced pressure the residue was partitioned between ethyl acetate and water The organic phase was dried under vacuum the title product was purified by column chromatography (SiO2, 20–30% ethyl acetate in hexanes) (0.370 g, 95%)

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Phosphorus pentachloride (40.53 g, 0.1947 mol) was added portionwise (caution, foaming) over 5 min at 25° C. to chlorosulfonic acid (56.8 g, 32.4 mL, 0.487 mol) and the resulting solution was stirred at 25° C. for 10 min. Then, 2-chlorofuran (20.0 g, 0.1947 mol) was added in one portion and the resulting dark suspension was heated to 55° C. for 1.0 h during which time foaming occurred and subsided. The reaction mixture was then poured onto ice and the resulting suspension was extracted with CH2Cl2 (250 mL). The organic was filtered through a pad of celite, washed with brine (70 mL) and dried over MgSO4. The solvent was removed in vacuo to provide 5-chlorofuran-2-sulfonyl chloride as a black oil (14.1 g, 36.02%). 1H-NMR (DMSO-d6, 400 MHz) δ 7.05 (d, 1H); 6.35 (d, 1 H). the resulting dark suspension was heated to 55° C. for 1.0 h during which time The reaction mixture was then poured onto ice the resulting suspension was extracted with CH2Cl2 (250 mL) The organic was filtered through a pad of celite washed with brine (70 mL) dried over MgSO4 The solvent was removed in vacuo