Structure of 21560-29-2
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CAS No. : | 21560-29-2 |
Formula : | C11H10ClNO2 |
M.W : | 223.66 |
SMILES Code : | COC1=CC2=C(C=C1OC)C=CN=C2Cl |
MDL No. : | MFCD16249956 |
InChI Key : | MPMDYPSDYGHVBM-UHFFFAOYSA-N |
Pubchem ID : | 10640708 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H320-H335 |
Precautionary Statements: | P261-P280-P301+P312-P302+P352-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 |
---|---|---|
87% | With potassium tert-butylate;palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In tetrahydrofuran; toluene; at 80℃; for 4.33333h;Heating / reflux; | 6,7-Dimethoxy-3',4'-dihydro-1'H-[1,2']biisoquinolinyl. Palladium acetate (25 mg 0.112 mmol) and 2,2'-bis(diphenylphosphino)-1,1'-binaphtyl (209 mg, 0.335 mmol) were heated to 80 C. in toluene (25 mL) for 20 min. To the mixture was added 500 mg (2.24 mmol) of <strong>[21560-29-2]1-chloro-6,7-dimethoxy-isoquinoline</strong>, 298 mg (2.24 mmol) of tetrahydroisoquinoline, and 4.47 mL (4.47 mmol) of a 1.0 M solution of potassium tert-butoxide in THF. After stirring at reflux for 4 h, the mixture was diluted with EtOAc, washed with water, dried over MgSO4 and concentrated. Silica gel chromatography (4:1 hexanes/EtOAc) provided 625 mg (87%) of the title compound as a yellow oil. The hydrochloride salt (387 mg) was obtained after treatment with concd. HCl in isopropanol and recrystallization from EtOH/MeOH. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In methanol; chloroform; | EXAMPLE 5 <strong>[21560-29-2]1-Chloro-6,7-dimethoxyisoquinoline</strong> (0.63 g) and 6-(1-piperazinyl)-3,4-dihydro-2(1H)-quinolinone (1.30 g) were mixed at 200 C. for 1.5 hours under stirring. The mixture was dissolved in a mixture of chloroform and methanol (10:1 V/V) and subjected to a column chromatography on silica gel (eluent:methanol in chloroform, 0-2% V/V). The fractions containing the object compound were combined and concentrated and the residue was triturated with diisopropyl ether to give 6-[4-(6,7-dimethoxyisoquinolin-1-yl)-1-piperazinyl]-3,4-dihydro-2(1H)-quinolinone (0.44 g). mp: 235-240 C. IR (Nujol): 1670, 1620 cm-1 NMR (DMSO-d6, delta): 2.2-3.7 (12H, m), 3.96 (6H, s), 6.7-7.1 (3H, m), 7.2-7.6 (3H, m), 8.05 (1H, d, J=7 Hz), 9.88 (1H, br s) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate; In isopropyl alcohol; | Step A Preparation of 1-[4-(2-hydroxyethyl)-1-piperazino]-6,7-dimethoxyisoquinoline A mixture of 2.6 g. of <strong>[21560-29-2]1-chloro-6,7-dimethoxyisoquinoline</strong> and 6.0 g. of 2-hydroxyethylpiperazine is heated at 140C. for 2 hours and then combined with 50 ml. of isopropanol and 2 g. of sodium carbonate. The resulting mixture is refluxed for 15 minutes, filtered, evaporated in vacuo to an oil which is purified by chromatography on silica gel to obtain 1-[4-(2-hydroxyethyl)-1-piperazino]-6,7-dimethoxyisoquinoline, m.p. 115-118C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49.3% | With sodium hydride; In N,N-dimethyl acetamide; mineral oil; at 20 - 200℃; for 0.3h;Inert atmosphere; Microwave irradiation; | A solution of <strong>[21560-29-2]1-chloro-6,7-dimethoxyisoquinoline</strong> (50 mg, 0.22 mmol) and 4-fluorophenol (25.06mg, 0.22 mmol) in DMA (3 mL) was stirred under a nitrogen atmosphere for 5 minutes.Sodium hydride (22.35 mg, 0.56 mmol; 60% in mineral oil) was added to the reaction mixture and stirred at ambient temperature for 15 minutes. Next the mixture was stirred and heated at 200C for 3 minutes under microwave irradiation. The reaction mixture was quenched with methanol (0.5 mL) and the crude material was purified by flash column chromatography eluting with a gradient of ethyl acetate and methanol (1:0 to 1:1) to give a gum. The product was purified by reverse phase chromatography and the desired product (33.0 mg,49.3%) was obtained as a solid. HPLC purity:>99% (215 nM), >99% (254 nM), >99% (280 nM). 1H NMR (400MHz, DMSO-d6) d ppm 3.94 (s, 3 H), 3.92 (s, 3 H), 7.23- 7.31 (m, 4 H), 7.36 - 7.43 (m, 2 H), 7.58 (s, 1 H), 7.76 (d, J=5.5 Hz, 1 H).HRMS m/z calcd for C17H14FNO3 [M+H]+300.1031, found 300.1030. |
49.3% | A solution of <strong>[21560-29-2]1-chloro-6,7-dimethoxyisoquinoline</strong>(50 mg, 0.22 mmol) and 4-fluorophenol (25.06 mg, 0.22 mmol) in DMA (3 mL) wasstirred under a nitrogen atmosphere for 5 minutes. Sodium hydride (22.35 mg,0.56 mmol; 60% in mineral oil) was added to the reaction mixture and stirred atambient temperature for 15 minutes. Next the mixture was stirred and heated at 200C for 3 minutes undermicrowave irradiation. The reaction mixture was quenched with methanol (0.5 mL)and the crude material was purified by flash column chromatography eluting witha gradient of ethyl acetate and methanol (1:0 to 1:1) to give a gum. Theproduct was purified by reverse phase chromatography and the desired product (33.0mg, 49.3%) was obtained as a solid. HPLCpurity: >99% (215 nM), >99% (254 nM), >99% (280 nM). 1H NMR(400 MHz, DMSO-d6) dppm 3.94 (s, 3 H), 3.92 (s, 3 H), 7.23 - 7.31 (m, 4 H), 7.36- 7.43 (m, 2 H), 7.58 (s, 1 H), 7.76 (d, J=5.5 Hz, 1 H). HRMS m/z calcd for C17H14FNO3[M+H]+ 300.1031, found 300.1030. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45.4% | With trichlorophosphate; In acetonitrile; at 110℃; for 0.0833333h;Microwave irradiation; | A solution of 6,7-dimethoxyisoquinolin-1(2H)-one(200 mg, 0.97 mmol), phosphoryl trichloride (0.268 mL, 2.92 mmol) in acetonitrile (5 mL) was stirred at 110C for 5 minutes under microwave irradiation. The reaction was quenched with a saturated aqueous sodium bicarbonate solution and stirred at ambient temperature for 1 h. It was filtered through celite and washed with ethyl acetate. The filtrate was concentrated to dryness.The crude material was purified by flash chromatography, eluting with heptanes and ethyl acetate (1:0 to 0:1) to give the desired product as a gum (99 mg,45.4 %). MS m/z 224.0 [M+H]+ (ESI). |
With trichlorophosphate; In acetonitrile; at 110℃; for 0.0833333h;Microwave irradiation; | General procedure: A solution of 6,7-dimethoxyisoquinolin-1(2H)-one(200 mg, 0.97 mmol), phosphoryl trichloride (0.268 mL, 2.92 mmol) inacetonitrile (5 mL) was stirred at 110 C for 5 minutes under microwaveirradiation. The reaction was quenched with a saturated aqueous sodium bicarbonatesolution and stirred at ambient temperature for 1 h. It was filtered throughcelite and washed with ethyl acetate. The filtrate was concentrated to dryness.The crude material was purified by flash chromatography, eluting with heptanesand ethyl acetate (1:0 to 0:1) to give the desired product as a gum (99 mg,45.4 %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
34% | With N,N-dimethyl-formamide; trichlorophosphate; In dichloromethane; at 40℃; for 6h;Inert atmosphere; Reflux; | General procedure: The procedure is identical to general procedure I, except that reactions were conducted at 0.2 M concentration with N-oxide (1.00 equiv), POBr3 (3.00 equiv), DMF (1.50 equiv) at rt. 4.2 General procedure I for the bromination of azine N-oxides (0013) To a stirred solution of the appropriate azine N-oxides in anhydrous CH2Cl2 (0.1 M) at 0 C is added POBr3 (1.2 equiv) followed by dropwise addition of DMF (0.5 equiv) under argon. The resulting reaction mixture was warmed to 25 C and stirred for several hours until the reaction is complete as indicated by TLC. Saturated aqueous sodium carbonate solution is added to the reaction mixture slowly to adjust the pH to 7-8. The resulting mixture is separated and the aqueous phase is extracted with CH2Cl2 thoroughly. The organic phase is combined and washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure to afford the crude product, which is purified by flash column chromatography using PE/EA (100:1) as eluent. |
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