cyclobutanesulfonamide

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

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

Procedure: Prepared from 14-tert-butoxycarbonylamino-18-(isoquinolin-1-yloxy)-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.04,6]-nonadec-7-ene-4-carboxylic acid etherate (114 mg, 0.192 mmol) and cyclobutanesulfonic acid amide (34 mg, 0.25 mmol) as described in the general procedure above. Flash chromatography (2% methanol/methylene chloride) gave 73 mg (58%) of [18-(isoquinolin-1-yloxy)-4-(1-methyl-cyclopropanesulfonylaminocarbonyl)-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.04,6]nonadec-7-en-14-yl]-carbamic acid tert-butyl ester as a white powder: LC-MS (Method A, retention time: 3.55 min), MS m/z 710 (M++1).

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared from (3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)-3-methylpiperidin-2-one (Example 91, Step B, 250 mg, 0.560 mmol) and cyclobutanesulfonamide (Example 271G, 256 mg, 1.894 mmol) using the general procedure described in Step A of Example 272, albeit with an oil bath heated at 40° C. The crude product was purified by silica gel chromatography eluting with a gradient of EtOAc in hexanes. The product was obtained as a white powder (220 mg, 70%). LCMS (ESI): m/z=563.2 (M+H). described in Step A of Example 272, albeit with an oil bath The crude product was purified by silica gel chromatography eluting with a gradient of EtOAc in hexanes

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared from (3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)-3-methylpiperidin-2-one (Example 91, Step B, 250 mg, 0.560 mmol) and cyclobutanesulfonamide (Example 271G, 256 mg, 1.894 mmol) using the general procedure described in Step A of Example 272, albeit with an oil bath heated at 40° C. The crude product was purified by silica gel chromatography eluting with a gradient of EtOAc in hexanes. The product was obtained as a white powder (220 mg, 70%). LCMS (ESI): m/z=563.2 (M+H). described in Step A of Example 272, albeit with an oil bath The crude product was purified by silica gel chromatography eluting with a gradient of EtOAc in hexanes

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared from (3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)-3-methylpiperidin-2-one (Example 91, Step B, 250 mg, 0.560 mmol) and cyclobutanesulfonamide (Example 271G, 256 mg, 1.894 mmol) using the general procedure described in Step A of Example 272, albeit with an oil bath heated at 40° C. The crude product was purified by silica gel chromatography eluting with a gradient of EtOAc in hexanes. The product was obtained as a white powder (220 mg, 70%). LCMS (ESI): m/z=563.2 (M+H). described in Step A of Example 272, albeit with an oil bath The crude product was purified by silica gel chromatography eluting with a gradient of EtOAc in hexanes

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

Procedure: Prepared from 14-tert-butoxycarbonylamino-18-(isoquinolin-1-yloxy)-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.04,6]-nonadec-7-ene-4-carboxylic acid etherate (114 mg, 0.192 mmol) and cyclobutanesulfonic acid amide (34 mg, 0.25 mmol) as described in the general procedure above. Flash chromatography (2% methanol/methylene chloride) gave 73 mg (58%) of [18-(isoquinolin-1-yloxy)-4-(1-methyl-cyclopropanesulfonylaminocarbonyl)-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.04,6]nonadec-7-en-14-yl]-carbamic acid tert-butyl ester as a white powder: LC-MS (Method A, retention time: 3.55 min), MS m/z 710 (M++1).

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

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

Procedure: A mixture of (2R,6S,7R,13aS,14aR,16aS,Z)-6-((tert-butoxycarbonyl)amino)-2-((4-methoxyisoquinolin-1-yl)oxy)-7,9-dimethyl-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a-carboxylic acid (70 mg, 0.108 mmol), CDI (34.9 mg, 0.215 mmol) in tetrahydrofuran (3 mL) was refluxed for 2 h. It was then cooled to rt and cyclobutanesulfonamide (32.0 mg, 0.237 mmol) was added and followed by DBU (0.036 mL, 0.237 mmol). The mixture was stirred at rt for 16 h. It was then concentrated and purified by silica gel chromatography, eluting with 40% acetone/hexane to isolate 70 mg of the diastereomers tert-butyl ((2R,6S,7R,13aS,14aR,16aS,Z)-14a-((cyclobutylsulfonyl)carbamoyl)-2-((4-methoxyisoquinolin-1-yl)oxy)-7,9-dimethyl-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecin-6-yl)carbamate that was used as it was. was refluxed for 2 h It was then concentrated purified by silica gel chromatography eluting with 40% acetone/hexane

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared from (3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)-3-methylpiperidin-2-one (Example 91, Step B, 250 mg, 0.560 mmol) and cyclobutanesulfonamide (Example 271G, 256 mg, 1.894 mmol) using the general procedure described in Step A of Example 272, albeit with an oil bath heated at 40° C. The crude product was purified by silica gel chromatography eluting with a gradient of EtOAc in hexanes. The product was obtained as a white powder (220 mg, 70%). LCMS (ESI): m/z=563.2 (M+H). described in Step A of Example 272, albeit with an oil bath The crude product was purified by silica gel chromatography eluting with a gradient of EtOAc in hexanes

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared from (3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)-3-methylpiperidin-2-one (Example 91, Step B, 250 mg, 0.560 mmol) and cyclobutanesulfonamide (Example 271G, 256 mg, 1.894 mmol) using the general procedure described in Step A of Example 272, albeit with an oil bath heated at 40° C. The crude product was purified by silica gel chromatography eluting with a gradient of EtOAc in hexanes. The product was obtained as a white powder (220 mg, 70%). LCMS (ESI): m/z=563.2 (M+H). described in Step A of Example 272, albeit with an oil bath The crude product was purified by silica gel chromatography eluting with a gradient of EtOAc in hexanes

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

Procedure: Prepared from 14-tert-butoxycarbonylamino-18-(isoquinolin-1-yloxy)-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.04,6]-nonadec-7-ene-4-carboxylic acid etherate (114 mg, 0.192 mmol) and cyclobutanesulfonic acid amide (34 mg, 0.25 mmol) as described in the general procedure above. Flash chromatography (2% methanol/methylene chloride) gave 73 mg (58%) of [18-(isoquinolin-1-yloxy)-4-(1-methyl-cyclopropanesulfonylaminocarbonyl)-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.04,6]nonadec-7-en-14-yl]-carbamic acid tert-butyl ester as a white powder: LC-MS (Method A, retention time: 3.55 min), MS m/z 710 (M++1).