cyclobutane

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: This compound was prepared from methyl Z-2-(1-tert-butyloxycarbonyloxycyclobutyloxyimino)-2-(fur-2-yl)acetate as described in Preparation 7(b), m.p. 133°-134°. λmax (EtOH) 284 nm (ε15,900), νmax (Nujol) 3500-2100 (bonded OH), 1750 (CO2H), 1708 cm-1 (α,β-unsaturated --CO2R), τ(DMSO d6) 7.2-8.5 (cyclobutane), 2.1, 3.12, 3.33 (furyl), 6.09 (--CO2CH3). Yield 94%

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

実験手順: This compound was prepared from Z-2-(1-tertbutyloxycarbonylcyclobutyloxyimino)-2-(fur-2-yl)acetic acid as described in Preparation 7(a). λmax (EtOH) 281.5 nm (ε17,000), νmax (Nujol) 1745 (--CO2R), 1723 cm-1 (α,β-unsaturated --CO2R), τ(DMSO d6) 8.59 (--C(Me)3), 7.3-8.4 (cyclobutane), 2.1, 3.15, 3.35 (furyl), 6.09 (--CO2CH3). Yield 98%.

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

実験手順: This compound was prepared from Z-2-(1-tertbutyloxycarbonylcyclobutyloxyimino)-2-(fur-2-yl)acetic acid as described in Preparation 7(a). λmax (EtOH) 281.5 nm (ε17,000), νmax (Nujol) 1745 (--CO2R), 1723 cm-1 (α,β-unsaturated --CO2R), τ(DMSO d6) 8.59 (--C(Me)3), 7.3-8.4 (cyclobutane), 2.1, 3.15, 3.35 (furyl), 6.09 (--CO2CH3). Yield 98%.

反応条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of (1,1-dioxo-1λ6-thiomorpholin-4-yl)-[1-isopropyl-5-(piperidin-4-yloxy)-1H-indol-2-yl]-methanone (268 mg, 1.0 eq.) in acetic acid (115 mg, 3.0 eq.) was added a solution of cyclobutane (90 mg, 2.0 eq.) in tetrahydrofuran (8 mL). The mixture was stirred for 2 h at 55° C. Then the mixture was cooled to room temperature and sodium triacetoxyborohydride (279 mg, 2.0 eq.) was added. The reaction mixture was stirred overnight at 65° C. The residue was partitioned between water and ethyl acetate. The organic layer was washed with a sodium hydrogenocarbonate aqueous solution, dried over sodium sulfate, filtered and dried in vacuo. Then the residue was purified on silica eluting with a gradient of dichloromethane/methanol to yield 97 mg (32%) of the desired product as off-white oil. MS (m/e): 474.5 (MH+, 100%). Then the mixture was cooled to room temperature The reaction mixture was stirred overnight at 65° C The residue was partitioned between water and ethyl acetate The organic layer was washed with a sodium hydrogenocarbonate aqueous solution dried over sodium sulfate filtered dried in vacuo Then the residue was purified on silica eluting with a gradient of dichloromethane/methanol

反応条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of (1,1-dioxo-1λ6-thiomorpholin-4-yl)-[1-isopropyl-5-(piperidin-4-yloxy)-1H-indol-2-yl]-methanone (268 mg, 1.0 eq.) in acetic acid (115 mg, 3.0 eq.) was added a solution of cyclobutane (90 mg, 2.0 eq.) in tetrahydrofuran (8 mL). The mixture was stirred for 2 h at 55° C. Then the mixture was cooled to room temperature and sodium triacetoxyborohydride (279 mg, 2.0 eq.) was added. The reaction mixture was stirred overnight at 65° C. The residue was partitioned between water and ethyl acetate. The organic layer was washed with a sodium hydrogenocarbonate aqueous solution, dried over sodium sulfate, filtered and dried in vacuo. Then the residue was purified on silica eluting with a gradient of dichloromethane/methanol to yield 97 mg (32%) of the desired product as off-white oil. MS (m/e): 474.5 (MH+, 100%). Then the mixture was cooled to room temperature The reaction mixture was stirred overnight at 65° C The residue was partitioned between water and ethyl acetate The organic layer was washed with a sodium hydrogenocarbonate aqueous solution dried over sodium sulfate filtered dried in vacuo Then the residue was purified on silica eluting with a gradient of dichloromethane/methanol

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: This compound was prepared from methyl Z-2-(1-tert-butyloxycarbonyloxycyclobutyloxyimino)-2-(fur-2-yl)acetate as described in Preparation 7(b), m.p. 133°-134°. λmax (EtOH) 284 nm (ε15,900), νmax (Nujol) 3500-2100 (bonded OH), 1750 (CO2H), 1708 cm-1 (α,β-unsaturated --CO2R), τ(DMSO d6) 7.2-8.5 (cyclobutane), 2.1, 3.12, 3.33 (furyl), 6.09 (--CO2CH3). Yield 94%

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

実験手順: This compound was prepared from Z-2-(1-tertbutyloxycarbonylcyclobutyloxyimino)-2-(fur-2-yl)acetic acid as described in Preparation 7(a). λmax (EtOH) 281.5 nm (ε17,000), νmax (Nujol) 1745 (--CO2R), 1723 cm-1 (α,β-unsaturated --CO2R), τ(DMSO d6) 8.59 (--C(Me)3), 7.3-8.4 (cyclobutane), 2.1, 3.15, 3.35 (furyl), 6.09 (--CO2CH3). Yield 98%.

反応条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of (1,1-dioxo-1λ6-thiomorpholin-4-yl)-[1-isopropyl-5-(piperidin-4-yloxy)-1H-indol-2-yl]-methanone (268 mg, 1.0 eq.) in acetic acid (115 mg, 3.0 eq.) was added a solution of cyclobutane (90 mg, 2.0 eq.) in tetrahydrofuran (8 mL). The mixture was stirred for 2 h at 55° C. Then the mixture was cooled to room temperature and sodium triacetoxyborohydride (279 mg, 2.0 eq.) was added. The reaction mixture was stirred overnight at 65° C. The residue was partitioned between water and ethyl acetate. The organic layer was washed with a sodium hydrogenocarbonate aqueous solution, dried over sodium sulfate, filtered and dried in vacuo. Then the residue was purified on silica eluting with a gradient of dichloromethane/methanol to yield 97 mg (32%) of the desired product as off-white oil. MS (m/e): 474.5 (MH+, 100%). Then the mixture was cooled to room temperature The reaction mixture was stirred overnight at 65° C The residue was partitioned between water and ethyl acetate The organic layer was washed with a sodium hydrogenocarbonate aqueous solution dried over sodium sulfate filtered dried in vacuo Then the residue was purified on silica eluting with a gradient of dichloromethane/methanol