2-chloro-4-fluorobenzenesulfonyl chloride

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-Chloro-4-fluorobenzenesulfonyl chloride (1.16 g; 5.0 mmol) was added to a cold solution (ice:water temperature) of 3-chloro-5-[2-(4-cyanophenyl)-ethoxy]phenol (0.689 g; 2.5 mmol; from step (ii) above) in pyridine (8 mL). The temperature was allowed to rise (slowly) to ambient overnight. The mixture was re-cooled (ice:water temperature) and ice was added to the reaction flask. After stirring for 4 hours, the pyridine was removed in vacuo. CH2Cl2 was then added and the organic layer was washed with aqueous KHSO4 and water. Drying (MgSO4), evaporation of the solvent and purification by flash chromatography (SiO2; CH2Cl2) afforded 0.84 g (72%) of the sub-title compound. to ambient overnight was added to the reaction flask the pyridine was removed in vacuo CH2Cl2 was then added the organic layer was washed with aqueous KHSO4 and water Drying (MgSO4), evaporation of the solvent and purification by flash chromatography (SiO2; CH2Cl2)

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Chloro-4-fluorobenzenesulphonyl chloride (85.7 mg, 0.37 mmol) was added to a solution of (4-Amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-(3-amino-phenyl)-methanone (80 mg, 0.25 mmol) in pyridine (3 mL). The resulting solution was heated to 120° C. for 3 h. The reaction was quenched with water and concentrated. The residue was dissolved in EtOAc and washed with 1N NaOH (1×) and water (1×). The organic layer was dried over Na2SO4 and concentrated. Purification by flash column chromatography (CH2Cl2/MeOH 98:2) afforded the title compound as a white solid (32 mg, 25%). MS: 514.1/516.1 (MH+); HPLC Rf: 6.12 min. (HPLC method 4). The reaction was quenched with water concentrated The residue was dissolved in EtOAc washed with 1N NaOH (1×) and water (1×) The organic layer was dried over Na2SO4 concentrated Purification by flash column chromatography (CH2Cl2/MeOH 98:2)

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

Procedure: Prepared from 8-(4-amino-benzyl)-3-butyl-1-(2-fluoro-benzyl)-3,7-dihydro-purine-2,6-dione and 2-chloro-4-fluoro-benzenesulfonyl chloride. Purity (ELSD, based on MW=614.1)=93%.

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

Procedure: The product was prepared according to General Procedure 6, described in Example 65, with 2-chloro-4-fluorobenzenesulfonyl chloride (12.6 mg, 0.055 mmol) and 5-(3-aminophenyl)tetrazole (8.0 mg, 0.050 mmol). The title compound was obtained in 62% yield (10.9 mg). MS (ESI+) calcd mass for C13H9ClFN5O2S 353.014951, found 353.015041. The product was prepared

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

Procedure: 2-Chloro-4-flourobenzenesulfonyl chloride (29.5 mg) was added to tert-butyl 4-(1H-pyrrolo[3,2-c]pyridin-4-yl)piperazine-1-carboxylate the title compound (2.4 mg). LC/MS RT: 1.361 (System 10 till 40% MeCN over 1.5 min, ACE C8), Purity. 90%. MS: 396 (M+1)

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

Procedure: 2-Chloro-4-flourobenzenesulfonyl chloride (29.5 mg) was added to tert-butyl 4-(1H-pyrrolo[3,2-c]pyridin-4-yl)piperazine-1-carboxylate the title compound (2.4 mg). LC/MS RT: 1.361 (System 10 till 40% MeCN over 1.5 min, ACE C8), Purity. 90%. MS: 396 (M+1)

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

Procedure: In a similar manner to Step 1 of Example 233, 4-hydroxy-7-[1-(tert-butoxycarbonyl)-5-(piperidinomethyl)indol-2-yl]isoindolinone (0.0290 g, 0.0628 mmol) was dissolved in acetonitrile (0.650 mL), and the solution was treated with triethylamine (0.0540 mL, 0.390 mmol) and 2-chloro-4-fluorobenzenesulfonyl chloride (0.0447 g, 0.195 mmol) to obtain 4-(2-chloro-4-fluorobenzenesulfonyloxy)-7-[1-(tert-butoxycarbonyl)-5-(piperidinomethyl)indol-2-yl]isoindolinone (0.0133 g, yield 34%).

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: In a similar manner to Step 1 of Example 233, 4-hydroxy-7-[1-(tert-butoxycarbonyl)-5-(piperidinomethyl)indol-2-yl]isoindolinone (0.0290 g, 0.0628 mmol) was dissolved in acetonitrile (0.650 mL), and the solution was treated with triethylamine (0.0540 mL, 0.390 mmol) and 2-chloro-4-fluorobenzenesulfonyl chloride (0.0447 g, 0.195 mmol) to obtain 4-(2-chloro-4-fluorobenzenesulfonyloxy)-7-[1-(tert-butoxycarbonyl)-5-(piperidinomethyl)indol-2-yl]isoindolinone (0.0133 g, yield 34%).