5-chloroisoindoline hydrochloride

A mixture of Compound 151A (340 mg, 2.36 mmol) and 1-(azidomethyl)-4- methoxybenzene (500 mg, 3.07 mmol) in toluene (15 mL) was stirred at 110 C for 48 hours. The reaction mixture was concentrated and purified by column chromatography on silica gel using ethyl acetate- hexane as eluent to afford a Mixture 151B. LC-MS (ESI) m/z: 278 [M+H]._A Mixture 151B (60 mg, 0.217 mmol) and thionyl chloride (0.45 mL) in methylene chloride (10 mL) was stirred at 50 C for 5 hours. The reaction mixture was concentrated to give isic, which was used directly in the next step without further purification.LC-MS (ESI) m/z: 296 [M+H]._ A Mixture 151C (74 mg, 0.2 17 mmol), 5-chloroisoindoline (38 mg, 0.248 mmol), and K2C03 (60 mg, 0.43 5 mmol) in DMF (6 mL) was stirred at 60 C for 5 hours. The mixture was poured into water (100 mL) and extracted with ethyl acetate (100 mL x 3). The combined extracts were washed with brine (200 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified with preparative HPLC to afford a Mixture 151D. LCMS (ESI) m/z: 413 [M+H]tA mixture of Compound 151A (340 mg, 2.36 mmol) and 1-(azidomethyl)-4- methoxybenzene (500 mg, 3.07 mmol) in toluene (15 mL) was stirred at 110 C for 48 hours. The reaction mixture was concentrated and purified by column chromatography on silica gel using ethyl acetate- hexane as eluent to afford a Mixture 151B. LC-MS (ESI) m/z: 278 [M+H]._A Mixture 151B (60 mg, 0.217 mmol) and thionyl chloride (0.45 mL) in methylene chloride (10 mL) was stirred at 50 C for 5 hours. The reaction mixture was concentrated to give isic, which was used directly in the next step without further purification.LC-MS (ESI) m/z: 296 [M+H]._ A Mixture 151C (74 mg, 0.2 17 mmol), 5-chloroisoindoline (38 mg, 0.248 mmol), and K2C03 (60 mg, 0.43 5 mmol) in DMF (6 mL) was stirred at 60 C for 5 hours. The mixture was poured into water (100 mL) and extracted with ethyl acetate (100 mL x 3). The combined extracts were washed with brine (200 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified with preparative HPLC to afford a Mixture 151D. LCMS (ESI) m/z: 413 [M+H]tA mixture of Compound 151A (340 mg, 2.36 mmol) and 1-(azidomethyl)-4- methoxybenzene (500 mg, 3.07 mmol) in toluene (15 mL) was stirred at 110 C for 48 hours. The reaction mixture was concentrated and purified by column chromatography on silica gel using ethyl acetate- hexane as eluent to afford a Mixture 151B. LC-MS (ESI) m/z: 278 [M+H]._A Mixture 151B (60 mg, 0.217 mmol) and thionyl chloride (0.45 mL) in methylene chloride (10 mL) was stirred at 50 C for 5 hours. The reaction mixture was concentrated to give isic, which was used directly in the next step without further purification.LC-MS (ESI) m/z: 296 [M+H]._ A Mixture 151C (74 mg, 0.2 17 mmol), 5-chloroisoindoline (38 mg, 0.248 mmol), and K2C03 (60 mg, 0.43 5 mmol) in DMF (6 mL) was stirred at 60 C for 5 hours. The mixture was poured into water (100 mL) and extracted with ethyl acetate (100 mL x 3). The combined extracts were washed with brine (200 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified with preparative HPLC to afford a Mixture 151D. LCMS (ESI) m/z: 413 [M+H]tGeneral procedure: A mixture of Intermediate J (200 mg, 0.66 mmol), Compound 146A, 3-(4-chlorophenyl)pyrrolidine, (143 mg, 0.79 mmol), HATEG (380 mg, 1 mmol), and DIPEA ( 258 mg, 2 mmol) in DMF (5 mL) was stirred at room temperature overnight. The mixture was diluted with EtOAc (50 mL), washed with brine (15 mL x 3), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified with preparative HPLC give Compound 146B. LC-MS (ESI) m/z: 469 [M +H]+.A mixture of 2-chloro-N-(1 H-indazol-5-yl)-5 , 7-dihydro furo[3 , 4-d]pyrimidin- 4-amine (1.0 g ), ZiniI.8 g, 7.8 mmcl) and 1.0g of 2-(p-toluensulphonyl)-5-chloroisoindoline and 1.0g of phenol were added to a mixture of 8 ml of 48percent hydrobromic acid and 1.4 ml of propionic acid, and then mixture was heated at reflux for 6 hours. The resultant reaction mixture was diluted with 10ml of water and extracted twice with 50ml of ethyl acetate. The water layer was basified with aqueous sodium hydroxide solution and extracted with ethyl acetate three times. The extract was concentrated and the crude product was diluted with 4N HCI/dioxane and stirred for 15minut.es before evaporating the HCI and then re-evaporating with toluene three times to give 0.3g of 5-chloro-2, 3-dihydro-1 H-isoindole hydrochloride as a black solid. MS: [M+H]+ 153-151.Og of 2-(p-toluensulphonyl)-5-chloroisoindoline and 1.0g of phenol were added to a mixture of 8 ml of 48percent hydrobromic acid and 1.4 ml of propionic acid, and then mixture was heated at reflux for 6 hours. The resultant reaction mixture was diluted with 10ml of water and extracted twice with 50ml of ethyl acetate. The water layer was basified with aqueous sodium hydroxide solution and extracted 1.Og of 2-(p-toluensulphonyl)-5-chloroisoindoline and 1.Og of phenol were added to a mixture of 8 ml of 48percent hydrobromic acid and 1.4 ml of propionic acid, and then mixture was heated at reflux for 6 hours. The resultant reaction mixture was diluted with 10ml of water and extracted twice with 50ml of ethyl acetate. The water layer was basified with aqueous sodium hydroxide solution and extracted with ethyl acetate three times. The extract was concentrated and the crude product was diluted with 4N HCI/dioxane and stirred for 15minut.es before evaporating the HCI and then re-evaporating with toluene three times to give 0.3g of 5-chloro-2, 3-dihydro-1 H-isoindole hydrochloride as a black solid. MS: [M+H]+ 153-15.Og of 2-(p-toluensulphonyl)-5-chloroisoindoline and 1.Og of phenol were added to a mixture of 8 ml of 48percent hydrobromic acid and 1.4 ml of propionic acid, and then mixture was heated at reflux for 6 hours. The resultant reaction mixture was diluted with 10ml of water and extracted twice with 50ml of ethyl acetate. The water layer was basified with aqueous sodium hydroxide solution and extracted with ethyl acetate three times. The extract was concentrated and the crude product was diluted with 4N HCI/dioxane and stirred for 15minut.es before evaporating the HCl and then re-evaporating with

Molecular Weight:190.07
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:1
Exact Mass:189.0112047
Monoisotopic Mass:189.0112047
Topological Polar Surface Area:12
Heavy Atom Count:11
Complexity:126
Covalently-Bonded Unit Count:2
Compound Is Canonicalized:Yes