Structure of 124480-95-1
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CAS No. : | 124480-95-1 |
Formula : | C11H14O4 |
M.W : | 210.23 |
SMILES Code : | O=C(O)C1=CC(OCC)=CC(OCC)=C1 |
MDL No. : | MFCD02063084 |
Boiling Point : | No data available |
InChI Key : | FCSNGXDTYSQXPA-UHFFFAOYSA-N |
Pubchem ID : | 721136 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With lithium hydroxide; In tetrahydrofuran; water; | The mono-alkylation of compound 12.2 is conducted by the treatment of 12.2 and NaH in DMF. Halide RDX (1 eq) is added to the reaction mixture to afford the corresponding aryl ether 12.3. The second alkylation is performed under the some conditions with halide REX [(1] eq), followed by basic hydrolysis (LiOH, [H20/THF)] to give acid 12.1 as the intermediate for use in making compounds like those described in Example 44. Illustrative examples of suitable halides and their corresponding final products are shown in Table 13. | |
With lithium hydroxide; water; In tetrahydrofuran; | This example describes the synthesis of compounds of the formula wherein RD and RE are each independently substituted or unsubstituted aliphatic or aromatic moieties. These compounds are prepared according to Scheme 8 and the procedure below. Compound 8.2 is treated with NaH in DMF, and halide RDX (1 eq) is added to the reaction mixture to yield aryl ether 8.3. Compound 8.3 is then treated with NaH in DMF, and halide REX (1 eq) is added. The reaction mixture is hydrolized (LiOH, H2O/THF) to give acid 8.1. Compounds 8.1, acids of the formula RCCOOH, are used to make additional compounds of the invention. Table 4 shows exemplary compounds 8.1's. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; HATU; In N,N-dimethyl-formamide; at 20℃; | Example 2; To a mixture of N-[(dimethylamino)sulfonyl]-2-[(3-phenylpropyl)amino]methyl}-1,3-thiazole-4-carboxamide hydrochloride (10.5 mg), <strong>[124480-95-1]3,5-diethoxybenzoic acid</strong> (6.3 mg), triethylamine (10.4 μL), and DMF (0.50 mL) was added a HATU (11.4 mg)/DMF (0.10 mL) solution at room temperature, followed by stirring overnight. To the reaction mixture was added an appropriate amount of purified water, followed by extraction with CHCl3. The organic layer was concentrated under reduced pressure, and the obtained residue was purified by preparative high performance liquid chromatography (MeOH/0.1% aqueous formic acid solution) to prepare 2-[(3,5-diethoxybenzoyl)(3-phenylpropyl)amino]methyl}-N-[(dimethylamino)sulfonyl]-1,3-thiazole-4-carboxamide (9.2 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | 3,5-Diethoxybenzoic acid (49.8 mg, 0.237 mmol) and 1-[bis(dimethylamino)methylene]- 1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (108 mg, 0.284 mmol, HATU) was dissolved in a mixture of dry N,N-dimethylformamide (1 mL), tetrahydrofuran (1.000 mL) and N,Ndiisopropylethylamine (92 mg, 0.711 mmol). The mixture was stirred for 20 minutes at room temperature. Then Example 133-Step 1 (60 mg, 0.237 mmol) was added, and the solution was stirred for another 3 hours at room temperature. The mixture was poured into water and extracted with ethyl acetate 3 times. The combined organic layers were washed with brine, dried over Na2504, and concentrated. The residue was purified by flash column chromatography on silica gel (loaded directly with CH2C12) eluted with hexanes and ethyl acetate (0-50%) to give the titled compound (80 mg, 0.180 mmol, 76% yield). LC-MS (ESI) m/z 446.2 (M+H)t |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
175 mg | With N-ethyl-N,N-diisopropylamine; O-(benzotriazol-1-yl)-N,N,N,N-tetramethyluroniumhexafluorophosphate; In N,N-dimethyl-formamide; at 20℃; | A mixture of 2-(2-pyridyl)-5 ,6,7 , 8-tetrahydropyrido [4,3-d]pyrimidine hydrochloride (300 mg, 0.92 mmol, the product of step 3 in Example 1), <strong>[124480-95-1]3,5-diethoxybenzoic acid</strong> (387 mg, 1.84 mmol), HATU (699 mg, 1.84 mmol) and DIPEA (595 mg, 4.6 mmol) in DMF (5 mL) was stirred at rt overnight. The resulting mixture was poured into water (5 mL) and extracted withEA (20 mL) for three times. The combined organic layer was concentrated in vacuo and the residue was purified by prep-HPLC to give (3,5-diethoxyphenyl)-[2-(2-pyridyl)-7,8-dihydro-5H- pyrido[4,3-d]pyrimidin-6-yl]methanone (175 mg) as light yellow solid. ‘H NMR (400 MHz, CDC13) ö: 8.80-8.94 (m, 1H), 8.72 (d, 1H), 8.51 (d, 1H), 7.87 (td, 1H), 7.41 (ddd, 1H), 6.45-6.62 (m, 3H), 4.58-5.05 (m, 2H), 3.71-4.13 (m, 6H), 3.05-3.32 (m, 2H), 1.28-1.55 (m, 6H). MS obsd.(ESI)[(M+H)]: 405. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 1h;Inert atmosphere; | General procedure: To a solution of the above intermediate (0.21 mmol) in anhydrous DMF (3 mL), a solution of a carboxylic acid (0.22 mmol) in DMF (1 mL) was added dropwise followed by the addition of HBTU (0.22 mmol) and DIPEA (0.43 mmol). The reaction mixture was stirred at room temperature for 1h under Ar. Brine (10 mL) was added and the solid formed was filtered, washed with water (2 x 10 mL), hexane (10 mL) and hexane:EtOAc (4:1 mixture, 5 mL) and dried to give the desired compound which was recrystallized from DMSO:H2O. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With dicyclohexyl-carbodiimide; In tetrahydrofuran; at 0 - 20℃; | 2, 3, 4, 2’, 3’, 4’ -Hexakis-6>-tri methyl si lyl-a,a-trehalose (prepared as described in (0513) Johnson et al. J Carbohydr. Chem. 17(6), 969-974 (1998)) (412 mg, 0.53 mmol), 3,5- diethoxybenzoic acid (276 mg, 1.31 mmol) and 4-(dimethylamino)pyridinium 4-toluenesulfonate (77mg, 0.26 mmol) were dissolved in THF (10 mL) with magnetic stirring and the solution cooled to 0-5 C in an ice bath. DCC was added and the reaction was allowed to warm to ambient temperature and stirred until the starting trehalose intermediate was consumed as determined by TLC. The crude reaction mixture was purified by chromatography on silica gel with a heptane to ethyl acetate gradient yielding 366 mg (60%) 2,3,4,2’,3,,4’-Hexakis-0- trimethylsilyl-6,6’-bis-(3,5-dimethoxybenzoate)-a,a-trehalose. |
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