Category: 924304-73-4

Electric Literature of 924304-73-4, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 924304-73-4 name is 4-Chloroisoindoline hydrochloride, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.

Step 4: Synthesis of (3J?,5S)-1-((S)-4-(but-3-enyIoxy)-2-(tert- butoxycarbonylamino)butanoyl)-5-((li?,25)-1-(ethoxycarbonyl)-2- vinylcyclopropylcarbamoyl)pyrrolidin-3-yl 4-chIoroisoindoline-2-carboxylate[0489] (17?,25)-ethyl l-((25,4i)-1-((5)-4-(but-enyloxy)-2-(tert- butoxycarboalphaylamino)butanoyl)-4-hydroxypyrrolidine-2-carboxamido)-2- vinylcyclopropanecarboxylate (0.55 g, 1.1 mmol) in THF (20 mL) was added 1,1 ‘- carbonyldiimidazole (0.204 g, 1.26 mmol) in one portion. The reaction was stirred at room temperature for 3 hours. To the reaction was then added the N-ethyl-N-isopropylpropan-2- amine (0.92 mL, 5.3 mmol), followed by 4-chloroisoindoline hydrochloride (0.258 g, 1.37 mmo.). The reaction was stirred at 50 C for 18 hours. The solvent was removed. The residue was partitioned between ethyl acetate (20 mL) and saturated sodium bicarbonate solution. The organic layer was separated and dried over sodium sulfate. After removal of solvent, the residue was purified by chromatography (HexanerEthyl acetate=l :3) to give (3i?,5£)-1-((S)-4- (but-3-enyloxy)-2-(tert-butoxycarbonylamino)butanoyi)-5-(( IR,2S)- 1 -(ethoxycarbonyl)-2- vinylcyclopropylcarbamoyl)pyrrolidin-3-yl 4-chloroisoindoline-2-carboxylate as white solid (0.49 g, 66%). MS: Calcd.: 702.3; Found: [M+H]+ 703.1.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 4-Chloroisoindoline hydrochloride, and friends who are interested can also refer to it.

Reference:
Patent; INTERMUNE, INC.; ARRAY BIOPHARMA, INC.; WO2008/137779; (2008); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 924304-73-4, name is 4-Chloroisoindoline hydrochloride, This compound has unique chemical properties. The synthetic route is as follows., Formula: C8H9Cl2N

Step 3: Synthesis of (2Jff,65>,13a5′,14ai?,16a5rZ)-ethyI 6-(tert-butoxycarbonylamino)-2-(4- chloroisoindoline-2~carbonyloxy)-5,16-dioxo-2,3,5,6,7,8,9,ll,13a,14,14a,15,16,16a- tetradecahydro-lH-cyclopropa(e)pyrrolo[2,l-i][l,7,10joxadiazacyclopentadecine-14a- carboxylate[0472] (2R,6S, 13aS, 14aR, 16aS,Z)-ethyl 6-(tert-butoxycarbonylamino)-2-hydroxy- 5,16-dioxo~2,3,5,6,7,8,9,l l,13a,14,14a,15,16,16a4etradecahydro-1H- cyclopropa(e)pyrrolo[2,l-/][l,7,10]oxadiazacyciopentadecine-14a-carboxylate (0.30 g, 0.61 mmol) in toluene (5 mL) was added lj ‘-carbonyldiimidazole (0.12 g, 0.73 ramol) in one portion. The reaction was stirred at room temperature for 3 hours. To the reaction was then added the N-ethyl-N-isopropylpropan-2-amine (0.53 mL, 3.0 mmol), followed by 4- chloroisoindoline hydrochloride salts (0.15 g, 0.79 mmol). The reaction was stirred at 60 C for 3 hours. The solvent was removed. The residue was partitioned between ethyl acetate (20 mL) and saturated sodium bicarbonate solution. The organic layer was separated and dried over sodium sulfate. After removal of solvent, the residue was purified by chromatography (etaexanerEthyl acetate=l:3) to give (2/?,65,13a5,14aR,16a5’,Z)-ethyI 6-{tert- butoxycarbonylamino)-2-(4-chloroisoindoline-2-carbonyloxy)-5,16-dioxo- 2,3,5,6,7,8,9,11, 13a,14,14a,15,16,16a-tetradecahydro-1H-cyclopropa(phiyrrolo[2,l- /][l,7,10]oxadiazacyclopentadecine-14a-carboxylate as white solid (0.18 g, 86%). MS: Calcd.: 674.3; Found: [M+eta]+ 675.1.

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 924304-73-4.

Reference:
Patent; INTERMUNE, INC.; ARRAY BIOPHARMA, INC.; WO2008/137779; (2008); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 924304-73-4, Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 924304-73-4, name is 4-Chloroisoindoline hydrochloride, This compound has unique chemical properties. The synthetic route is as follows.

Step 4: Synthesis of (3J?,5S)-1-((S)-4-(but-3-enyIoxy)-2-(tert- butoxycarbonylamino)butanoyl)-5-((li?,25)-1-(ethoxycarbonyl)-2- vinylcyclopropylcarbamoyl)pyrrolidin-3-yl 4-chIoroisoindoline-2-carboxylate[0489] (17?,25)-ethyl l-((25,4i)-1-((5)-4-(but-enyloxy)-2-(tert- butoxycarboalphaylamino)butanoyl)-4-hydroxypyrrolidine-2-carboxamido)-2- vinylcyclopropanecarboxylate (0.55 g, 1.1 mmol) in THF (20 mL) was added 1,1 ‘- carbonyldiimidazole (0.204 g, 1.26 mmol) in one portion. The reaction was stirred at room temperature for 3 hours. To the reaction was then added the N-ethyl-N-isopropylpropan-2- amine (0.92 mL, 5.3 mmol), followed by 4-chloroisoindoline hydrochloride (0.258 g, 1.37 mmo.). The reaction was stirred at 50 C for 18 hours. The solvent was removed. The residue was partitioned between ethyl acetate (20 mL) and saturated sodium bicarbonate solution. The organic layer was separated and dried over sodium sulfate. After removal of solvent, the residue was purified by chromatography (HexanerEthyl acetate=l :3) to give (3i?,5?)-1-((S)-4- (but-3-enyloxy)-2-(tert-butoxycarbonylamino)butanoyi)-5-(( IR,2S)- 1 -(ethoxycarbonyl)-2- vinylcyclopropylcarbamoyl)pyrrolidin-3-yl 4-chloroisoindoline-2-carboxylate as white solid (0.49 g, 66%). MS: Calcd.: 702.3; Found: [M+H]+ 703.1.

The chemical industry reduces the impact on the environment during synthesis 4-Chloroisoindoline hydrochloride. I believe this compound will play a more active role in future production and life.

Reference:
Patent; INTERMUNE, INC.; ARRAY BIOPHARMA, INC.; WO2008/137779; (2008); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 924304-73-4, name is 4-Chloroisoindoline hydrochloride, This compound has unique chemical properties. The synthetic route is as follows., Computed Properties of C8H9Cl2N

Compound 26; Step 2: Synthesis of (2S,4R)-1-(tert-butoxycarbonyl)-4-(4-chloroisoindoline-2- carbonyloxy)pyrrolidine-2-carboxylic acid; To a solution of (25″,4lambda)-1-tert-butyI 2-methyl 4-hydroxypyitauolidme-1,2- dicarboxylate (500 mg, 2 04 mmol) in dry THF (6 mL) was added CDI (430 mg, 2 65 mmol) m one portion and the mixture was stirred at rt for 6 h The amine, 4-chloroisomdoline hydrochloride (0 89 g, 4 7 mmol) was then added in portions, followed by slow addition of DIEA (1 07 mL, 6.12 mmol). The reaction was stirred at rt for overnight. The reaction was diluted with 120 mL EtOAc, washed with IN HCl (2 x 50 mL), water and brine (50 mL each), and dried over Na2SO4 and concentrated down to a thick brownish oil The crude was purified by silica chromatography (eluent = hexanes/EtOAc 2 1), giving the ester product, (25,4J?)-1-tert-butyl 2-methyl 4-(4-chloroisoindolme-2-carbonyloxy)pyrrolidine-1,2- dicaiboxylate, as a light pinkish foamy solid (0 79 g, 91 % yield); (25′,4R)-1-(tert-butoxycarbonyl)-4-(4-chloroisoindoIine-2-carbonyloxy)pyrrolidine-2- carboxylic acid; To a solution of (2S,4R)- 1 -tert-butyl 2-methyl 4-hydroxypyrrolidine-1,2- dicarboxylate (0.50 g, 2.04 mmol) in dry THF (6 niL) was added CDI (430 mg, 2.65 mmol) in one portion and the mixture was stirred at rt for 6 h. 4-chloroisoindoline hydrochloride (0.89 g, 4.69 mmol) was then added in portions, followed by slow addition of DIEA (1.07 mL, 6.12 mmol). The reaction was stirred at rt for overnight. The reaction was diluted with 120 mL EtOAc, washed with IN HCl (2 x 50 mL), water and brine (50 mL each), and dried over Na2SC>4 and concentrated down to a thick brownish oil. The crude was purified by silica chromatography (eluent = hexanes/EtOAc 2: 1), giving (2S,4R)-1-tert-butyl 2-methyl 4-(4- chloroisoindoIine-2-carbonyloxy)pyrrolidine-l ,2-dicarboxylate as a light pinkish foamy solid (0.79 g, 91 % yield).

According to the analysis of related databases, 924304-73-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; INTERMUNE, INC.; ARRAY BIOPHARMA; WO2008/141227; (2008); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem