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CAS No. : | 23687-26-5 | MDL No. : | MFCD04114862 |
Formula : | C9H8N2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | NGFCTYXFMDWFRQ-UHFFFAOYSA-N |
M.W : | 144.17 | Pubchem ID : | 588991 |
Synonyms : |
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Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H319 | Packing Group: | N/A |
GHS Pictogram: |
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* 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 |
---|---|---|
80% | With hydrazine hydrate; at 80℃; under 4137.29 Torr; for 0.75h;Microwave irradiation; | A mixture of 1u (100 mg, 0.81 mmol), hydrazine hydrate (121.5mg, 2.43 mmol), and SS-Rh (370 mg, 2 molpercent Rh) were taken in an oven dried reaction tube equipped with screw cap. 0.5 ml of PEG-400 was added into the reaction mixture. The reaction was then irradiated in a microwave apparatus at 80°C , 80 W for 10 min with a pressure of 80 Psi. After cooling to ambient temperature in the microwave cavity the reaction mixture was extracted with ethyl acetate (3x2 ml) and water (1ml). The combined organic layer wasdried over anhydrous Na2SO4 and the solvent was removed under reduced pressure and after purificationwith silica gel column chromatography (hexane: EtOAc= 90:10) 2u asyellowish liquid (63 mg, 80percent).1H and 13C NMR spectra hasbeen compared with our previously reported study |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | In pyridine; water; | Preparation Example 21 6-(4-Toluenesulfonylamino) isoquinoline In pyridine (30 ml) was dissolved <strong>[23687-26-5]6-aminoisoquinoline</strong> (3.348 g, Synthesis, 733 (1975), and 4-toluenesulfonyl chloride (5.13 g) was added thereto, followed by stirring at room temperature overnight. Water was added thereto, followed by extracting with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate and the solvent was evaporated. The residue was recrystallized from ethanol, to give the title compound (5.958 g, 85%) as pale yellow crystals. 1H-NMR (DMSO-d6) delta (ppm): 2.28 (3H, s), 7.32 (2H, d, J=8.2 Hz), 7.40 (1H, dd, J=1.6, 9.2 Hz), 7.55 (1H, brs), 7.67 (1H, d, J=5.6 Hz), 7.74 (2H, d, J=8.2 Hz), 7.97 (1H, d, J=9.2 Hz), 8.36 (1H, d, J=5.6 Hz), 9.10 (1H, s). |
85% | In pyridine; water; | Production Example 21b 6-(4-Toluenesulfonylamino)isoquinoline 6-Aminoisoquinoline (3.348 g, Synthesis, 733 (1975)) was dissolved in pyridine (30 ml). To the mixture was added 4-toluenesulfonyl chloride (5.13 g), followed by stirring at room temperature overnight. Water was added thereto, and the mixture was extracted with ethyl acetate. The extract was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was recrystallized from ethanol, to give the title compound (5.958 g, 85%) as pale yellow crystals. 1H-NMR (DMSO-d6) delta (ppm): 2.28(3H, s), 7.32(2H, d, J = 8.2 Hz), 7.40(1H, dd, J = 1.6, 9.2 Hz), 7.55(1H, brs), 7.67(1H, d, J = 5.6 Hz), 7.74(2H, d, J = 8.2 Hz), 7.97(1H, d, J = 9.2 Hz), 8.36(1H, d, J = 5.6 Hz), 9.10(1H, s). |
85% | In pyridine; water; | PRODUCTION EXAMPLE 21b 6-(4-Toluenesulfonylamino)isoquinoline 6-Aminoisoquinoline (3.348 g, Synthesis, 733 (1975)) was dissolved in pyridine (30 ml). To the mixture was added 4-toluenesulfonyl chloride (5.13 g), followed by stirring at room temperature overnight. Water was added thereto, and the mixture was extracted with ethyl acetate. The extract was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was recrystallized from ethanol, to give the title compound (5.958 g, 85%) as pale yellow crystals. 1H-NMR (DMSO-d6) delta (ppm): 2.28(3H, s), 7.32(2H, d, J=8.2 Hz), 7.40(1H, dd, J=1.6, 9.2 Hz), 7.55(1H, brs), 7.67(1H, d, J=5.6 Hz), 7.74(2H, d, J=8.2 Hz), 7.97(1H, d, J=9.2 Hz), 8.36(1H, d, J=5.6 Hz), 9.10(1H, s). |
2.2 g | With pyridine; at 20℃; for 12h; | Isoquinolin-6-amine B24 (2.00 g, 13.87 mmol) was dissolved in pyridine (20 mL), and 4- methylbenzenesulfonyl chloride (3.17 g, 16.64 mmol) was added. The reaction mixture was stirred at 20C for 12 hours. LCMS showed the reaction was completed. To the reaction mixture was added water (30 mL) under good stirring, the mixture was stirred at 20C for 0.5 hour, pale yellow solid precipitated out. The mixture was filtered and the solid was collected and washed with water (5 mL) to give compound B25 (2.2g) as a yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Prepared from 3-{1-ethoxy-1-phenylmethylidene}-5-nitro-2-indolinone and 1.1 equivalents of an oily mixture of 2-Boc-6-amino-1,2,3,4-tetrahydro-isoquinoline [prepared from <strong>[23687-26-5]6-amino-isoquinoline</strong>, melting point 218-220° C., by catalytic hydrogenation to obtain 6-amino-1,2,3,4-tetrahydro-isoquinoline (melting point: 69-71° C.) and subsequent reaction with 0.9 equivalents of di-tert.butyl pyrocarbonate (=(Boc)2 O)] in DMF by heating to 100° C. for 3.5 hours, pouring into water, filtering and washing the precipitate with water and EtOH. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 1,1'-carbonyldiimidazole; In N-methyl-acetamide; dichloromethane; ethyl acetate; | EXAMPLE II N-(2-Hydroxyethyl)-N'-(isoquinolin-6-yl)-N-[4-[2-(methoxycarbonyl)ethyl]phenyl]-urea To 7.2 g of imidazole and 10.1 g of N,N'-carbonyldiimidazole in 100 ml of dimethylformamide are added dropwise, at a temperature of 0° to 10° C., 9.0 g of <strong>[23687-26-5]6-aminoisoquinoline</strong> in 70 ml of dimethylformamide. After 2 hours stirring at ambient temperature, 15.3 g of N-(2-hydroxyethyl)-4-[2-(methoxycarbonyl)ethyl]aniline in 20 ml of dimethylformamide are added dropwise and the mixture is stirred for 21/2 days at ambient temperature. The mixture is diluted with 750 ml of ethyl acetate and extracted twice with water and saturated saline solution. The organic phase is separated off, dried and evaporated down. The residue is purified by chromatography over a silica gel column using ethyl acetate/methylene chloride/methanol=70:30:10. Yield: 4.8 g (19percent of theory), Rf value: 0.48 (silica gel; methylene chloride/methanol/ethyl acetate=20:1:1) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 20℃; for 2h; | To a mixture of Intermediate 25.2 (0.054 mmol) in 1 mL CH3CN at rt, were added DIEA (14 muL, 0.082 mmol) and <strong>[23687-26-5]6-aminoisoquinoline</strong> (15.7 mg, 0.109 mmol). The mixture was stirred at rt for 2 h, then was diluted with EtOAc, washed with H2O and brine, dried (Na2SO4) and concentrated. The crude product was purified by flash chromatography (0 to 100percent EtOAc/hexanes gradient) to afford 22.5 mg of Intermediate 25.3 as a yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
33% | With pyridine; In dichloromethane; | (e) Benzenesulphonyl chloride (4.9 g, 0.028M) in CH2 Cl2 (15 ml) was added dropwise over 10 minutes to a cooled stirred mixture of <strong>[23687-26-5]6-aminoisoquinoline</strong> (4.0 g, 0.028M) and pyridine (2.37 g, 0.03M) in CH2 Cl2 (150 ml). The reaction mixture was stirred overnight at room temperature and was then washed with H2 O. The CH2 Cl2 solution was dried over MgSO4 and was then chromatographed on a silica gel column. After evaporation the residue was recrystallized from isopropanol to yield 6-phenylsulphonamidoisoquinoline (2.28 g, 33percent), m.p. 204°-6° C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In chloroform; | Synthetic Example 84b 6-(4-Chlorobenzenesulfonylamino)-1-cyanoisoquinoline The compound obtained using <strong>[23687-26-5]6-aminoisoquinoline</strong> (0.5 g, Synthesis, 733 (1975)) and 4-chlorobenzenesulfonyl chloride (0.88 g) in the same method as in Synthetic Example 1b was dissolved in chloroform (150 ml). Under ice-cooling, m-chloroperbenzoicacid (0.9 g) was added theterto, followed by stirring at room temperature overnight. The solvent was evaporated, and the resulting crystals were washed with diethyl ether, collected by filtration and dried, to give 6-(4-chlorobenzenesulfonylamino)isoquinoline-N-oxide (1.072 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38% | With lithium diisopropyl amide; In tetrahydrofuran; at -78 - 20℃; for 0.5h; | Step 1: Synthesis of 2-Chloro-7V-isoquinolin-6-yl-acetamide: A 2.0- mL vial equipped with a stirrer bar was charged with <strong>[23687-26-5]6-aminoisoquinoline</strong> (100 mg, 0.7 mmol) in THF (1.0 niL) and cooled to -78 °C. Lithium diisopropylamine (40 muL, 0.35 mmol) was added to the reaction at -78 °C followed by dropwise addition of chloroacetylchloride (62 muL, 0.7 mmol). The reaction was allowed to warm to room temperature and stirred for 30 min. The reaction was concentrated in vacuo then the solid was triturated with cold methanol. The solid was collected by filtration to afford 2-chloro-iV-isoquinolin-6-yl-acetamide (58 mg, 38percent). 1H NMR (400 MHz, DMSCW6) delta ppm 3.14 (s, 2H) 8.01 (dd, J=9.08, 1.66 Hz, IH) 8.45 (d, J-8.98 Hz, 2H) 8.66 (d, J=1.56 Hz, IH) 11.46 (s, IH); LCMS: 221 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 40℃; | To a solution of <strong>[23687-26-5]6-aminoisoquinoline</strong> (25 mg, 0.17 mmol) in DMF (1.0 mL) was added indoline-2-carboxylic acid (30 mg, 0.17 mmol), HATU (70 mg, 0.19 mmol), diisopropylethylamine (35 muL, 0.19 mmol) and stirred overnight at 40 °C. The reaction mixture was concentrated and purified by prep-HP LC to afford the titled compound (3.0 mg): 1H NMR (400 MHz, METHANOL-^) delta ppm 3.18 (dd, J=16.11, 8.30 Hz, IH) 3.56 (dd, J=16.20, 10.54 Hz, IH) 4.52 (dd, J-10.54, 8.40 Hz, IH) 6.70 - 6.81 (m, 2H) 6.99 - 7.10 (m, 3H) 7.73 (d, J=6.05 Hz, IH) 7.81 (dd, J=8.88, 2.05 Hz, IH) 8.05 (d, J=8.98 Hz, IH) 8.35 (d, J=5.86 Hz, IH) 8.40 (d, J-1.95 Hz, IH) 9.11 (s, IH); LCMS: 290 (M+H).[00178] This isoquinoline was also tested using the luciferase biochemical assay. The maximum inhibition was 110percent for GRK-2. The results in Ki (nM) using the scale above were as follows: GRK-2 - ++ GRK-3 - ++ GRK-5 - + EPO <DP n="39"/>GRK-6 - +. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
EXAMPLE 2 Preparation of N-(isoquinolin-6-yl)-3-phenylpropanamide (E2) To <strong>[23687-26-5]6-aminoisoquinoline</strong> in DMF cooled to 0° C. was added NaH and the solution was stirred for 30 minutes at 0° C. Then hydrocinnamoyl chloride was added and the mixture was stirred for 4 hours at room temperature. The mixture was diluted with EtOAc, extracted with NaHCO3(sat), dried (Na2SO4), filtered and evaporated. Column chromatography (SiO2, 10percent hexanes/EtOAc) gave N-(isoquilin-6-yl)-3-phenylpropanamide (E2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dmap; In N,N-dimethyl-formamide; at 20℃; for 4h; | EXAMPLE 88 Preparation of 1-benzyl-3-(isoquinolin-6-yl)urea (E88) To <strong>[23687-26-5]6-aminoisoquinoline</strong> in DMF is added DMAP and benzyl isocyanate and the solution was stirred at room temperature for 4 hours. The mixture was poured into NaHCO3 (sat), extracted with EtOAc, dried (Na2SO4), filtered and evaporated. Flash chromatography (SiO2, 5percent MeOH/CH2Cl2) provided 1-benzyl-3-(isoquinolin-6-yl) urea (E88). |
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