2-(3-Hydroxypropyl)-1H-isoindole-1,3(2H)-dione

White crystalline powder

3-Aminopropan-1-ol (10.0 g, 133.1 mmol) was dissolved in anhydrous toluene (100 ml). Phthalic anhydride (19.7 g, 133.1 mmol) was added and the reaction mixture was heated to 125 °C with stirring, under an atmosphere of argon for 6.5 h. After cooling to rt, the solvent was evaporated in vacuo to give phthalimide 5 (31.7 g, quantitative) as a white powder that required no further purification.General procedure: A mixture of phthalic anhydride (0.296 g, 2 mmol), amine (2.2 mmol), and phthalimide-N-sulfonic acid (0.091 g, 20 molpercent) in ethanol (5 ml) was stirred for 3 h at 80 °C. After completion (monitored by TLC), the insoluble catalyst was separated by filtration, washed with acetone, and dried (weight: 0.090 g, 99 percent recovered). The organic layer was concentrated under reduced pressure to give the desired product, washed with water, and recrystallized in ethanol (each product was dissolved in a minimum amountof hot ethanol and allowed to reach gradually to room temperature). In addition, some products needed extrapurification step by small column chromatography using the CH2Cl2/n-hexane solvent mixture (50:50).Step 1To a solution of 3 -aminopropan- 1 -ol ( 1.0 g, 13.1 mmol) and isobenzofuran- 1 , 3 -dione (2.0 g, 13.1 mmol) in toluene (25 mL, 3 mL/mmol) was added Et0.013mol phthalic anhydride in the three-neck flask, 0.013mol propanolamine was added dropwise at room temperature, the reaction was refluxed for 1.0H, cooled and the precipitated solid was recrystallized to give a white solid N- (3- hydroxypropyl) phthalimido imine 2.14g, 2-(3-((((3aR, 4R, 6R, 6aR)-6-(6-amino-9H-purin-9-yl)-2, 2-dimethyltetrahydrofuro[3, 4- d][l, 3]dioxol-4-yl)meth l)(methyl)amino)propyl)isoindoline-l, 3-dioneStep 1. Preparation of 2-(3-hydroxypropyl)isoindoIine-l, 3-dioneTo a solution of isobenzofuran-l , 3-dione (10.0 g, 135.1 mmol) in toluene (250 mL) was added 3-amino-l -propanol (10.0 g, 67.6 mmol) and the mixture was heated to reflux for 4 h under NIn a 10 ml reaction tube, adding phosphine nitrogen ligand L10a (0.35 mg, 0 . 65 μmol) with the three-phenyl phosphorus is great (0.48 mg, 0 . 50 μmol), system through the vacuum line, replace the nitrogen 3 times, and steams newly added new degassed toluene 2 ml, solution in 90 °C under stirring 3 hours, cooling to room temperature, solvent is removed under reduced pressure. At the same time in another 10 ml hydrogenation bottle, adding β - aminoketone laq (40.6 mg, 0.2 mmol) with anhydrous sodium carbonate (2.12 mg, 0 . 02 mmol), system through the vacuum line, replace the nitrogen 3 times. A syringe has been coordination of the new catalyst for steaming and new degassing of ethanol (3 ml) containing dissolved out and injected into the substrate and additive in the reaction tube, the reaction system is put in an autoclave, in 25 °C and HGeneral procedure: Amide (1.0 mmol), amine (1.0 mmol) and KGeneral procedure: To asolution of the PMB ether (1 mmol) in acetonitrile (10 mL), t-BuBr (1.1 equiv)was added and stirred at reflux. After completion of the reaction (monitored byTLC), it was concentrated under reduced pressure and the resulting crude wasdissolved in ethyl acetate (50 mL) and washed with saturated sodiumhydrogenocarbonate (25 mL). The aqueous layer was extracted with ethylacetate (2 5 mL) and the combine organic layer was washed with brinesolution, dried (MgSO4), concentrated under reduced pressure and the residuewas purified by column chromatography (silica gel, EtOAc, cyclohexane) toafford the corresponding alcohol.(e)

Molecular Weight:205.21
XLogP3:1.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:3
Exact Mass:205.07389321
Monoisotopic Mass:205.07389321
Topological Polar Surface Area:57.6
Heavy Atom Count:15
Complexity:253
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes