Phthaloyl dichloride

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Bromo-4,5-dimethoxylbenzeneethanamine (3.5 g 13.2 mmol) was dissolved and stirred in 50 mL dry acetonitrile. 2.14 mL (1.1 equiv) phthaloyl dichloride and 7 mL (3 equiv) Hünig's base were added. The mixture was stirred at room temperature overnight. Acetonitrile was removed; the remaining product was taken up in dichloromethane and washed with basic water (pH=11). The aqueous wash was extracted with dichloromethane 15 mL×3. The organic fractions were combined and dried over sodium sulfate. Solvent was removed to give the crude product, which was then purified by column chromatography. Calculated yield: 1.8 g (34%). Acetonitrile was removed washed with basic water (pH=11) The aqueous wash was extracted with dichloromethane 15 mL×3 dried over sodium sulfate Solvent was removed

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Phthaloyl dichloride (13.35 g; 92.2 mmol) was added to a cooled solution of 9-benzyloxyadenine (14.9 g, 61.5 mmol), 4-dimethylaminopyridine (1.5 g, 12.3 mmol) and triethylamine (25.7 ml, 184.4 mmol) in tetrahydrofuran (200 ml). After 1 hour at room temperature the solvent was removed under reduced pressure and the residue partitioned between chloroform (500 ml) and saturated potassium bicarbonate (300 ml). The organic phase was separated, washed with water (200 ml), brine (200 ml), dried (MgSO4) and evaporated to dryness. Column chromatography on silica gel eluting with chloroform-methanol (100:1) afforded the title compound (11.20 g, 49%). IR: υmax (KBr) 3070, 1800, 1740, 1730, 1605, 1585, 1450 and 1410 cm-1 ; 1H NMR δH [(CD3)2SO] 5.70(2H, s, CH2Ph), 7.55(5H, s, CH2Ph), 8.20(4H, s, Ar), 8.95(1H, s, H-2), 9.25(1H, s, H-8). Found: C, 64.71; H, 3.78; N, 18.85%; m/z 371.1025. C20H13N5O3 requires: C, 64.68; H, 3.54; N, 18.86%; m/e 371.1018. After 1 hour at room temperature the solvent was removed under reduced pressure the residue partitioned between chloroform (500 ml) and saturated potassium bicarbonate (300 ml) The organic phase was separated washed with water (200 ml), brine (200 ml) dried (MgSO4) evaporated to dryness

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-fluoromethyl-2-amino-5-methoxy-valeronitrile (1.62 g, 10 mmol) and triethylamine (2.02 g, 20 mmol) in methylene chloride (30 mL), cooled to -20° C., is added phthaloyldichloride (2.03 g, 10 mmol) in methylene chloride (10 mL). The mixture is allowed to warm up to room temperature overnight. After washing with water, 1 N HCl, water again, and drying (Na2SO4), the solvent is removed under reduced pressure to give 2.4 g (83%) of crude material. This is purified by chromatography on silica (ethyl acetate/petroleum ether 3:7). After washing with water, 1 N HCl, water again drying (Na2SO4) the solvent is removed under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-fluoromethyl-2-amino-5-methoxy-valeronitrile (1.62 g, 10 mmol) and triethylamine (2.02 g, 20 mmol) in methylene chloride (30 mL), cooled to -20° C., is added phthaloyldichloride (2.03 g, 10 mmol) in methylene chloride (10 mL). The mixture is allowed to warm up to room temperature overnight. After washing with water, 1 N HCl, water again, and drying (Na2SO4), the solvent is removed under reduced pressure to give 2.4 g (83%) of crude material. This is purified by chromatography on silica (ethyl acetate/petroleum ether 3:7). After washing with water, 1 N HCl, water again drying (Na2SO4) the solvent is removed under reduced pressure

反応条件: temp:17.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A five liter, three necked flask was equipped with a overhead stirrer, nitrogen atmosphere and addition funnel. The flask was charged with 636 g of 2-hydroxyethylacrylate (5.47 mol.), 547 g of triethylamine (5.41 mol.), 6 g of phenothiazine, 5 g of 4-dimethylaminopyridine and 3000 ml of tetrahydrofuran. The reaction was cooled to 17° C. with a water bath. Next, 563 g of phthaloyl chloride (2.75 mol.) was slowly added over 2.5 hours via the addition funnel. The reaction was stirred an additional 8 hours at room temperature. The triethylamine hydrochloride salt was removed by filtration and the mother liquor evaporated by rotoevaporation to yield an amber colored liquid. The liquid was placed under vacuum (15 mmHg, 2 kPa) and heated to 100° C. for one hour. The resulting liquid was collected to yield 995 g (99%) of the desired product. The product was confirmed by IR and 13C NMR. The preparation of di(acryloyloxyethyl)phthalate from phthalic anhydride and 2-hydroxyethylacrylate was reported in U.S. Pat. No. 3,336,418. A five liter, three necked flask was equipped with a overhead stirrer nitrogen atmosphere and addition funnel The triethylamine hydrochloride salt was removed by filtration the mother liquor evaporated by rotoevaporation to yield an amber colored liquid heated to 100° C. for one hour The resulting liquid was collected

反応条件: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of N-(2-aminopyrimidin-5-yl)(tert-butoxy)carboxamide (0.237 g, 1.0 mmol) in pyridine (1 mL) was added phthaloyl dichloride (0.144 mL, 1.0 mmol). The resulting suspension was stirred at 45° C. for 2 hr, diluted with EtOAc, washed with water and brine, dried and concentrated in vacuo to give crude (tert-butoxy)-N-[2-(1,3-dioxobenzo[c]azolidin-2-yl)pyrimidin-5-yl]carboxamide (0.31 g). ES-MS (M+H)+=341; (M+H−tBu)+=285. washed with water and brine dried concentrated in vacuo

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 1.0 g (5.8 mmol) of p-aminophenylsulfonamide in 3.6 mL of pyridine was added 878 μL (6.1 mmol) of phthalic dichoride. After heating to 60° C. for 18 h, the solution was poured into 1N HCl, cooled to 0° C., the precipitate was collected by filtration, and dried under vacuum to give 1.58 g (90%) of the titled compound. cooled to 0° C. the precipitate was collected by filtration dried under vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-fluoromethyl-2-amino-5-methoxy-valeronitrile (1.62 g, 10 mmol) and triethylamine (2.02 g, 20 mmol) in methylene chloride (30 mL), cooled to -20° C., is added phthaloyldichloride (2.03 g, 10 mmol) in methylene chloride (10 mL). The mixture is allowed to warm up to room temperature overnight. After washing with water, 1 N HCl, water again, and drying (Na2SO4), the solvent is removed under reduced pressure to give 2.4 g (83%) of crude material. This is purified by chromatography on silica (ethyl acetate/petroleum ether 3:7). After washing with water, 1 N HCl, water again drying (Na2SO4) the solvent is removed under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Pthaloyl chloride (0.089 g, 0.437 mmol) was added to a cold (0° C.) solution of 2-(2-Amino-pyrimidin-4-yl)-3-iodo-1-methyl-4-oxo-1,4,6,7-tetrahydro-pyrrolo-[3,2-c]-pyridine-5-carboxylic acid tert-butyl ester (prepared as described in Example 1) (0.158 g, 0.337 mmol) and pyridine (0.069 g, 0.875 mmol) in dry DCM (1.5 ml) and the reaction mixture was stirred at room temperature in argon atmosphere for 4 h. The organic layer was washed with a saturated solution of NaHCO3 (1×2.0 ml), brine (1×2.0 ml), and it was dried over Na2SO4. The filtrate was evaporated to dryness to give the crude product, which was purified by flash chromatography, over silica gel (DCM/MeOH (9.8:0.2) as eluent), to afford 2-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-pyrimidin-4-yl]-3-iodo-1-methyl-4-oxo-1,4,6,7-tetra-hydro-pyrrolo[3,2-c]pyridine-5-carboxylic acid tert-butyl ester (0.150 mg, 0.25 mmol, 74%). The organic layer was washed with a saturated solution of NaHCO3 (1×2.0 ml), brine (1×2.0 ml), and it was dried over Na2SO4 The filtrate was evaporated to dryness to give the crude product, which was purified by flash chromatography, over silica gel (DCM/MeOH (9.8:0.2) as eluent)

反応条件: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of N-(2-aminopyrimidin-5-yl)(tert-butoxy)carboxamide (0.237 g, 1.0 mmol) in pyridine (1 mL) was added phthaloyl dichloride (0.144 mL, 1.0 mmol). The resulting suspension was stirred at 45° C. for 2 hr, diluted with EtOAc, washed with water and brine, dried and concentrated in vacuo to give crude (tert-butoxy)-N-[2-(1,3-dioxobenzo[c]azolidin-2-yl)pyrimidin-5-yl]carboxamide (0.31 g). ES-MS (M+H)+=341; (M+H−tBu)+=285. washed with water and brine dried concentrated in vacuo