HazMat Fee +
There will be a HazMat fee per item when shipping a dangerous goods. The HazMat fee will be charged to your UPS/DHL/FedEx collect account or added to the invoice unless the package is shipped via Ground service. Ship by air in Excepted Quantity (each bottle), which is up to 1g/1mL for class 6.1 packing group I or II, and up to 25g/25ml for all other HazMat items.
| Type | HazMat fee for 500 gram (Estimated) |
| Excepted Quantity | USD 0.00 |
| Limited Quantity | USD 15-60 |
| Inaccessible (Haz class 6.1), Domestic | USD 80+ |
| Inaccessible (Haz class 6.1), International | USD 150+ |
| Accessible (Haz class 3, 4, 5 or 8), Domestic | USD 100+ |
| Accessible (Haz class 3, 4, 5 or 8), International | USD 200+ |
*Storage: {[sel_prStorage]}
*Shipping: {[sel_prShipping]}
The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
Isoquinoline is a pyridine analog that serves as the structural basis for numerous alkaloids with anticancer, anti-inflammatory, antidepressant, antibacterial, antimalarial, and anti-HIV activities.
4.5
*For Research Use Only! Not for Human Use. We Do Not Sell to Patients.
Change View
| Size | Price | VIP Price |
DE Stock US Stock |
Asia Stock Global Stock |
In Stock |
| {[ item.pr_size ]}{[ size_append_text(item.pr_size, proInfo.prAm, 'list') ]} |
Inquiry
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,1,item.pr_is_large_size_no_price, item.discount_usd) ]} {[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]} |
Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]} | {[ item.p_spot_brand_remark ]} 1-2 weeks {[ item.pr_usastock ]} In Stock Inquiry - | {[ item.p_spot_brand_remark ]} 1-2 weeks {[ item.pr_chinastock ]} {[ item.pr_remark ]} In Stock Inquiry - | Login - + |
Please Login or Create an Account to: See VIP prices and availability
Asia Stock: Ship in 3-5 business days
EU Stock: ship in 0-1 business day
Global Stock: ship in 7-10 days
US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days
{[ item.p_spot_brand_remark ]}
1-2weeks
Inquiry
Inquiry
{[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]}
{[ getRatePrice(item.pr_usd,1,item.mem_rate,item.pr_is_large_size_no_price, item.pr_usd) ]}
{[ item.p_spot_brand_remark ]}
1-2weeks
Inquiry
Inquiry
{[ getRatePrice(item.pr_usd,item.pr_rate,1,item.pr_is_large_size_no_price, item.vip_usd) ]}
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]}
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]}
In Stock
- +
Please Login or Create an Account to: See VIP prices and availability
Asia Stock: Ship in 3-5 business days
EU Stock: ship in 0-1 business day
Global Stock: ship in 7-10 days
US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Burton, Spencer T ; Lee, Gyunhee ; Moore, Curtis E ; Sevov, Christo S ; Turro, Claudia ;
Abstract: The Co(III) complexes, cis-[Co(ppy)2(L)]PF6, where ppy = 2-phenylpyridine and L = bpy (2,2′-bipyridine; 1), phen (1,10-phenanthroline; 2), and DAP (1,12-diazaperylene; 3), are reported and their photophysical properties were investigated to evaluate their potential as sensitizers for applications that include solar energy conversion schemes and photoredox catalysis. Calculations show that cyclometallation in the cis-[Co(ppy)2(L)]PF6 series affords strong Co(dπ)/ppy(π) orbital interactions that result in a Co/ppy(π*) highest occupied molecular orbital (HOMO) and a lowest unoccupied molecular orbital (LUMO) localized on the diimine ligand, L(π*). Complexes 1−3 exhibit relatively invariant oxidation potentials, whereas the reduction event is dependent on the identity of the diimine ligand, L, consistent with the theoretical predictions. For 3 a broad Co/ppy(π*) → L(π*) metal/ligand-to-ligand charge transfer (ML-LCT) absorption band is observed in CH3CN with a maxima at 507 nm, extending beyond 600 nm. Upon excitation of the 1 ML-LCT transition, transient absorption features consistent with the population of a 3ML-LCT excited state with lifetimes, τ, of 3.0 ps, 4.6 and 42 ps for 1, 2 and 3 in CH3CN respectively are observed. Upon irradiation with 505 nm, 3 is able to reduce methyl viologen (MV2+), an electron acceptor commonly in photocatalytic schemes. To our knowledge, 3 represents the first heteroleptic molecular Co(III) complex that combines cyclometallation with a diimine ligand with lowest-lying metal-to-ligand charge transfer excited states able to undergo photoinduced charge transfer with low-energy green light. As such, the structural design of 3 represents an important step toward d6 photosensitizers based on earth abundant metals.
Show More >
| CAS No. : | 119-65-3 |
| Formula : | C9H7N |
| M.W : | 129.16 |
| SMILES Code : | C12=C(C=NC=C2)C=CC=C1 |
| English Name : | Isoquinoline |
| MDL No. : | MFCD00006898 |
| InChI Key : | AWJUIBRHMBBTKR-UHFFFAOYSA-N |
| Pubchem ID : | 8405 |
| GHS Pictogram: | |
| Signal Word: | |
| Hazard Statements: | |
| Precautionary Statements: | |
| Class: | |
| UN#: | |
| Packing Group: |
* 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 |
|---|---|---|
| 92% | With [bis(acetoxy)iodo]benzene; chloroformic acid ethyl ester In 1,2-dichloro-ethane at 50℃; for 3 h; | General procedure: To an 8 mL dram vial was added iodobenzene diacetate (0.6 mmol, 1.5 equiv), and heteroarene(0.4 mmol, 1 eq.), anhydrous dichloroethane (1 mL), then chloride source (5 equiv). The solutionwas allowed to stir (1000 rpm) at 50 °C for the indicated amount of time. After which the solutionwas washed with saturated sodium bicarbonate, followed by saturated sodium thiosulfate andconcentrated. The crude mixture was then purified by column chromatography. |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With diethyl ether; ethylmagnesium bromide at 160℃; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 61% | With di-tert-butyl peroxide; yttrium(III) trifluoromethanesulfonate at 120℃; for 24h; Sealed tube; chemoselective reaction; | |
| 40% | With di-tert-butyl peroxide; iodine at 130℃; for 12h; Sealed tube; | General procedure: A general experimental procedure for this CDC is described asfollowing: an oven-dried reaction vessel was charged with isoquinoline(1a, 0.4 mmol, 1 equiv), I2 (0.02 mmol, 5.2 mg, 5mol%), DTBP (di-tert-butyl peroxide, 1.2 mmol, 3 equiv) in pxylene(1 mL) under air. The vessel was sealed and heated at 130°C for 12 h, then cooled to r.t. The resulting mixture was transferredto a silica gel column and eluted with hexanes and EtOAc(12:1) to give 1-(4-methylbenzyl)isoquinoline (3a) in 71% yieldas a yellow oil. |
| 15% | With ammonium peroxydisulfate; sulfuric acid; silver nitrate In water; acetonitrile at 50℃; for 3h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 92 % Turnov. | With Fe(OH)(OAc)2; trifluoroacetic acid; dibenzoyl peroxide In acetonitrile for 4h; Heating; | |
| With styrene; potassium hydroxide; trimethylsilyl cyanide; duvinyl resin-bound benzoyl chloride; lithium diisopropyl amide 1.) CH2Cl2, room temperature, 48 h, 2.) THF, -78 deg C, 30 min; -78 deg C to room temperature, 48 h, 2.) THF, H2O; Yield given. Multistep reaction; | ||
| Yield given. Multistep reaction; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 64% | With dipotassium peroxodisulfate; tetrabutylammomium bromide In 1,2-dichloro-ethane at 100℃; for 3h; | |
| 21% | With tert.-butylhydroperoxide; sulfuric acid; iron(II) sulfate In water at 5℃; for 2h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 3 steps 1: 82 percent / CH2Cl2 / Ambient temperature 2: 98 percent / sodium hydride / dimethylformamide / Ambient temperature 3: 9 percent / benzoic acid / xylene / Heating |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1: 69 percent / triethylbenzylammonmium chloride / CH2Cl2; H2O / 0.33 h / Irradiation; ultrasound sonication 2: 73 percent / 50percent aq. NaOH / tetrabutylammonium chloride / CH2Cl2 / 0.42 h / Ambient temperature; ultrasound sonication |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1: CH2Cl2; H2O / 48 h / 25 °C 2: DBU (1,8-diazabicyclo<5.4.0>undec-7-ene) / tetrahydrofuran / 1 h / 0 °C | ||
| Multi-step reaction with 2 steps 1: 65 percent / H2O / 4 h 2: 100 percent / sodium borohydride / ethanol / 2 h | ||
| Multi-step reaction with 2 steps 1: 3-chloro-benzenecarboperoxoic acid / chloroform / 1 h / 20 °C 2: triethylamine / acetonitrile / 18 h / Inert atmosphere; Reflux |
| Multi-step reaction with 2 steps 1: acetic acid; dihydrogen peroxide / 36 h / 70 °C 2: [bis(acetoxy)iodo]benzene / 1,2-dichloro-ethane / 80 °C | ||
| Multi-step reaction with 2 steps 1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 15 h / 0 - 20 °C 2: neat (no solvent) / 1 h / 130 °C / Sealed tube; Inert atmosphere | ||
| Multi-step reaction with 2 steps 1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 20 °C 2: triethylamine / acetonitrile / 20 °C / Inert atmosphere |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 3 steps 1: bromine / Erhitzen des Additionsprodukts auf 180-200grad 2: HNO3+H2SO4 3: tin dichloride; alcoholic hydrochloric acid |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 4 steps 2: aqueous H2SO4 3: ethanolic H2SO4 4: sodium ethylate; toluene / und anschliessend mit wss. Salzsaeure | ||
| Multi-step reaction with 4 steps 2: aqueous H2SO4 3: ethanolic H2SO4 4: sodium ethylate; toluene / und anschliessend mit wss. Salzsaeure | ||
| Multi-step reaction with 2 steps 1.1: trifluoromethylsulfonic anhydride / chloroform / 1 h / 20 °C / Inert atmosphere 1.2: 3 h / 60 °C / Inert atmosphere 1.3: 17 h / 60 °C / Inert atmosphere 2.1: tetrahydrofuran / 3 h / 20 °C / Inert atmosphere 2.2: 1 h / 80 °C |
| Multi-step reaction with 3 steps 1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 20 °C 2: triethylamine / acetonitrile / 20 °C / Inert atmosphere 3: diethyl ether; tetrahydrofuran / 3 h / -15 - 20 °C / Inert atmosphere |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 80% | With triethylamine In acetonitrile at 20℃; for 3h; regioselective reaction; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 25% | In ethanol at 20℃; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 79% | In ethanol at 20℃; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 78% | In ethanol at 20℃; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 80% | In ethanol at 20℃; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 90% | With cetyltrimethylammonim bromide; 1,8-diazabicyclo[5.4.0]undec-7-ene In water at 20℃; for 1h; | General reaction procedure for the synthesis of pyrrolo[2,1-a]isoquinolines: One mmol each of the isoquinoline (1a-b), phenacyl bromide/bromoacetic acid ester (2a-j), and chromone-3-carboxaldehyde (3a-c) derivatives were taken in a 100 ml RB flask. Then water (50 ml), CTAB (4 mmol) and DBU (1 mmol) were added and the mixture was stirred continuously for 1 h at room temperature. After completion of the reaction (monitored by TLC), the contents of the reaction mixture were poured into a separating funnel and extracted with ethyl acetate (3 × 25 ml). The organic layer was washed thoroughly with water until free from CTAB and base, dried over sodium sulfate, and evaporated to dryness in a rotary evaporator under reduced pressure. The residue was chromatographed over a column of silica gel (60-120 mesh) eluting with a mixture of hexane and ethyl acetate in different ratios, to yield the pyrrolo[2,1-a]isoquinolines (4a-x). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 90% | With cetyltrimethylammonim bromide; 1,8-diazabicyclo[5.4.0]undec-7-ene In water at 20℃; for 1h; | General reaction procedure for the synthesis of pyrrolo[2,1-a]isoquinolines: One mmol each of the isoquinoline (1a-b), phenacyl bromide/bromoacetic acid ester (2a-j), and chromone-3-carboxaldehyde (3a-c) derivatives were taken in a 100 ml RB flask. Then water (50 ml), CTAB (4 mmol) and DBU (1 mmol) were added and the mixture was stirred continuously for 1 h at room temperature. After completion of the reaction (monitored by TLC), the contents of the reaction mixture were poured into a separating funnel and extracted with ethyl acetate (3 × 25 ml). The organic layer was washed thoroughly with water until free from CTAB and base, dried over sodium sulfate, and evaporated to dryness in a rotary evaporator under reduced pressure. The residue was chromatographed over a column of silica gel (60-120 mesh) eluting with a mixture of hexane and ethyl acetate in different ratios, to yield the pyrrolo[2,1-a]isoquinolines (4a-x). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 56% | Isoquinoline ( 13a) (1.83 ml, 15.50 mmol) was added slowly to concentrated H2SO4 ( 17 ml) at 0C under stirring. The mixture was cooled at -25C and sodium borohydride (6.34 g, 35.65 mmol) was added at a rate such that the reaction temperature was maintained between -25C to -20C. The resulting reaction was continued for 1 hour at the said temperature and then allowed to reach at room temperature. The reaction mixture was poured into crushed ice and the pH was adjusted to 7.0 using concentrated aqueous N¾. The resulting slurry was stirred for 1 hour at 0C after which it was filtered and washed with ice-cold water. The crude product so obtained was air dried and purified by column chromatography to afford (2.5 g, 56%) 5,8-dibromoisoquinoline (13b). MS (EI) rn/z: 286 (M+l). ? NMR (400 MHz, DMSO-d6): 8 9.48 (s, 1H), 8.78 (d, J = 6 Hz, 1H), 8.06 (d, J = 8 Hz, 1H), 7.98 (dd, J = 6 Hz, J = 8 Hz, 2H). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 64% | With Trimethyl borate In tetrahydrofuran at 20℃; regioselective reaction; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 28% | With Trimethyl borate In tetrahydrofuran at 20℃; regioselective reaction; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 91% | With cetyltrimethylammonim bromide In water at 20℃; for 1.5h; Green chemistry; | General reaction procedure for the synthesis of thiazolo[2,3-a]isoquinolin-4-iumderivatives (4a-r) General procedure: One mmol each of the isoquinolines (1a-c), phenacyl bromide (2a-f)/ 2-bromoacetonitrile (2g), and benzoyl isothiocyanate (3) were taken in a 100 ml RB flask.Then water (50 ml), CTAB (4 mmol) and Amberlite resin 420 (1 mmol) were added andthe mixture was stirred continuously for 1.5 h at room temperature. After completion of the reaction (monitored by TLC), the solid was filtered off, washed thoroughly withwater (until free from CTAB), Then the solid was dried, and dissolved in chloroform andagain filtered to separate base (Amberlite resin 420) from solution. The compound furtherpurified by recrystallization from chloroform to yield the thiazolo[2,3-a]isoquinolin-4-ium derivatives (4a-r). |
| 90% | With cetyltrimethylammonim bromide In water at 20℃; for 1.5h; Green chemistry; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 77% | With sodium persulfate; [Ir(dF(CF3)ppy)2(dtbbpy)]PF6; trifluoroacetic acid In water at 23℃; for 2h; Inert atmosphere; Irradiation; regioselective reaction; | |
| 70% | With ammonium persulfate; 1-hydroxy-pyrrolidine-2,5-dione In water at 40℃; for 24h; Green chemistry; | |
| 60% | With ethanol; bis-[(trifluoroacetoxy)iodo]benzene In dimethyl sulfoxide; 1,2-dichloro-ethane at 20℃; for 12h; Schlenk technique; Inert atmosphere; Irradiation; diastereoselective reaction; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 95% | With Ethyl 2-mercaptopropionate; [4,4'-bis(1,1-dimethylethyl)-2,2'-bipyridine-N1,N1']bis[2-(2-pyridinyl-N)phenyl-C]iridium(III) hexafluorophosphate; toluene-4-sulfonic acid In dimethyl sulfoxide at 23℃; UV-irradiation; | |
| 78% | Stage #1: isoquinoline With 4-hydroxy-10,13-dimethoxydinaphtho[2,1-d:1’,2’-f][1,3,2]dioxaphosphepine 4-sulfide; trifluoroacetic acid In dichloromethane at 20℃; for 0.25h; Inert atmosphere; Darkness; Stage #2: ethanol In dichloromethane at 27 - 29℃; for 20h; Irradiation; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 1: 50% 2: 12% | Stage #1: isoquinoline With trifluoroacetic acid In ethyl acetate at 20℃; for 0.0833333h; Stage #2: propionaldehyde With oxygen In ethyl acetate at 100℃; for 96h; Sealed tube; | |
| 1: 33% 2: 38% | Stage #1: isoquinoline With trifluoroacetic acid In 1,2-dichloro-ethane at 20℃; for 0.0833333h; Stage #2: propionaldehyde With oxygen In 1,2-dichloro-ethane at 0 - 115℃; for 25h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 50% | With triethylamine In dichloromethane at 20℃; for 24.5h; Inert atmosphere; Reflux; | General procedure for synthesis of compounds 3, 5, 7, 8, 10, 15, 20 and 21 General procedure: The corresponding cycloimmonium salt (1mmol, 1equiv) and ethyl cyanoformate (1.1mmol, 1.1equiv) were added to 5mL of dichloromethane and the obtained suspension was stirred under N2 atmosphere at room temperature (rt). Triethylamine (TEA) (3mmol, 3equiv) was added drop-wise over 30min (magnetic stirring) and the resulting mixture was then stirred for 24h at room temperature or reflux. Methanol (5mL) was added and the resulting mixture was kept for 24h without stirring. In most of the reaction a precipitate formed and it was collected by filtration to give a powder which was washed with few mL methanol. The product was crystallized from an appropriate solvent. For every reaction mixture, parallel, we carried out column chromatography of the reaction mixture in order to identify eventual coproducts. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 90% | With [Ir(dF(CF3)ppy)2(dtbbpy)]PF6; trifluoroacetic acid In N,N-dimethyl acetamide at 20℃; for 6h; Schlenk technique; Inert atmosphere; Irradiation; regioselective reaction; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 94% | With [Ir(dF(CF3)ppy)2(dtbbpy)]PF6; indium(III) tosylate In N,N-dimethyl acetamide at 20℃; for 6h; Schlenk technique; Inert atmosphere; Irradiation; regioselective reaction; | |
| 28% | With tris(2,2'-bipyridyl)ruthenium dichloride; toluene-4-sulfonic acid In N,N-dimethyl-formamide at 20℃; for 48h; Inert atmosphere; Irradiation; | 3.3. General Procedure B: Coupling of N-Hydroxyphthalimide Esters with Heterocycles 3, 5-18 General procedure: A 10 mL vial equipped with a stirrer bar and a septum was flushed with argon and charged withdry N,N’-dimethylformamid. The solvent was previously degassed by ultrasonication (see GerneralInformation). The N-hydroxyphthalimide ester (0.30 mmol, 1.50 equiv.), the heterocyclic compound(0.20 mmol, 1 equiv.), p-toluenesulfonic acid monohydrate (0.30 mmol, 1.50 equiv.) and Ru(bpy)3Cl2(2 mol, 1 mol %) were added, followed by argon sparging for 1 min. The mixture was irradiated witha blue LED module from a distance of 5 cm for 48 h. A saturated aqueous NaHCO3 solution (30 mL)was added, followed by extraction with dichloromethane (3 x 15 mL). The combined organic layers were dried over MgSO4 and concentrated under reduced pressure. Flash column chromatographyafforded the desired product. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 74% | With dipotassium peroxodisulfate In water at 100℃; Sealed tube; Green chemistry; | 3. Typical Experimental Procedure for Acylation of Isoquinoline: General procedure: To a solution of isoquinoline 1a (0.5 mmol) in water (2 mL) was added keto acid 2a (1.25 mmol), followed by K2S2O8 (1.5 mmol). The reaction mixture contained in a sealed tube was heated at 100 °C for 4-6 h. The contents were then cooled in an ice-bath and quenched with the saturated solution of sodium bicarbonate. The resulting mixture was extracted with ethyl acetate (2 × 10 mL) The organic phase was washed with water, dried over anhydrous sodium sulphate and evaporated under diminished pressure to afford the crude residue. The residue was finally purified by column chromatography to obtain the pure acylated product 3a. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 88% | Stage #1: isoquinoline; 2-oxo-propionic acid With Selectfluor; trifluoroacetic acid In dichloromethane; water at 20℃; for 0.0166667h; Stage #2: With silver nitrate In dichloromethane; water at 50℃; | |
| 76% | With ammonium peroxydisulfate; [Ir(dFMeppy)2(dtbbpy)]PF6 In dimethyl sulfoxide at 20℃; for 12h; Inert atmosphere; Irradiation; Green chemistry; regioselective reaction; | Procedure B for compounds (5a-5z,5bb) in Schemes 3 General procedure: Heterocycle (0.10mmol, 1 equiv)ammonium persulfate (0.20 mmol, 2equiv),[Ir{dF(CF3ppy)}2(dtbbpy)]PF6 ( 0.2 mol%),α-keto acids(1.0mmol10equiv)wereplaced in a dry glass tube.Then, anhydrous DMSO1mLwereinjected into the tubeby syringe under a N2 atmosphere.The solution was then stirred at roomtemperatureunder the irradiation of 15W blue LEDs strip for 12h.After completion of thereaction,then saturated Na2CO3solution was added to adjust pH to basic.Thecombined organic layer was washed with brine and then dried overanhydrousNa2SO4.The desired products were obtained in thecorresponding yields afterpurification by flashchromatography on silica gel eluting with petroleum andethylacetate. |
| 70% | With dipotassium peroxodisulfate In water at 100℃; Sealed tube; | 3. Typical Experimental Procedure for Acylation of Isoquinoline: General procedure: To a solution of isoquinoline 1a (0.5 mmol) in water (2 mL) was added keto acid 2a (1.25 mmol), followed by K2S2O8 (1.5 mmol). The reaction mixture contained in a sealed tube was heated at 100 °C for 4-6 h. The contents were then cooled in an ice-bath and quenched with the saturated solution of sodium bicarbonate. The resulting mixture was extracted with ethyl acetate (2 × 10 mL) The organic phase was washed with water, dried over anhydrous sodium sulphate and evaporated under diminished pressure to afford the crude residue. The residue was finally purified by column chromatography to obtain the pure acylated product 3a. |
| 67% | With Anthrone; trifluoroacetic acid In 1,2-dichloro-ethane at 25℃; Irradiation; | 3. General procedure for acylation of N-heterocycles General procedure: A 5-mL screw-capped reaction tube equipped with a magnetic stir bar was filled with anthrone (0.06 mmol, 0.3 equiv.), α-keto acid (0.60 mmol, 3 equiv.) TFA(0.02mmol,0.1 equiv) and N-heterocycle (0.20 mmol, 1 equiv.), followed by the addition of 1,2-dichloroethane(1.0 mL) under air. Then, the reaction tube was placed approximately 2 cm away from each 8×5W Violet bulbs (see picture of the reaction set-up). The reaction mixture was allowed to stir at room temperature and irradiated with 8×5 W Violet bulbs for 12 hours (vial temperature reached 45 °C).The reaction mixture became darker and a color change from slight yellow to orange/brown was generally observed after the transformation (see pictures of the reaction mixtures). After opening of the reaction tube, off-gassing was observed. Subsequently, the solution was diluted with DCM (10 mL), washed with an aqueous saturated solution of NaHCO3 (10 mL) and extracted with DCM (2 ×10 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered off and concentrated under reduced pressure to afford the crude product. The crude product was purified by column chromatography on silica gel to provide the desired compound. |
| 64% | With ferrous(II) sulfate heptahydrate; ammonium peroxydisulfate; formic acid; dimethyl sulfoxide In dichloromethane; water at 40℃; | Typical procedure for the non-noble metal catalyzed Minisci acylation reaction General procedure: N-heteroarene (1 mmoL, 80 mg), α-keto acid (3 mmol), Formic acid (1 mmol, 38 μL), ammonium persulfate (3 mmoL, 685 mg), ferrous sulfate heptahydrate (0.08 mmoL, 22 mg) and 20 mL of mixed solvent (DCM: H2O = 3: 1) , 0.1 mL DMSO was added into a 25 mL round-bottomed flask. The mixture was stirred at 40 oC until TLC analysis indicating that the reaction was complete (witnessed by the disappearance of the N-heteroarene). After separation of organic phase, the residue was neutralized by 0.1 M sodium hydroxide solution, then extracted with DCM (3×20 mL), combined the organic phases, dried over Na2SO4, and concentrated in vacuo. The residue was N-heteroarene (1 mmoL, 80 mg), α-keto acid (3 mmol), Formic acid (1 mmol, 38 μL), ammonium persulfate (3 mmoL, 685 mg), ferrous sulfate heptahydrate (0.08 mmoL, 22 mg) and 20 mL of mixed solvent (DCM: H2O = 3: 1) , 0.1 mL DMSO was added into a 25 mL round-bottomed flask. The mixture was stirred at 40 oC until TLC analysis indicating that the reaction was complete (witnessed by the disappearance of the N-heteroarene). After separation of organic phase, the residue was neutralized by 0.1 M sodium hydroxide solution, then extracted with DCM (3×20 mL), combined the organic phases, dried over Na2SO4, and concentrated in vacuo. The residue was purified by column chromatography on silica gel using a mixture of petroleum ether/EtOAc (v : v = 20 : 1) as eluent to afford the desired pure product. |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 86% | With ethanol; bis-[(trifluoroacetoxy)iodo]benzene In dimethyl sulfoxide; 1,2-dichloro-ethane at 20℃; for 12h; Schlenk technique; Inert atmosphere; Irradiation; | |
| 75% | With ammonium persulfate; 1-hydroxy-pyrrolidine-2,5-dione In water at 40℃; for 24h; Green chemistry; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 100% | With tris(2,2'-bipyridyl)ruthenium dichloride; toluene-4-sulfonic acid In N,N-dimethyl-formamide at 20℃; for 48h; Inert atmosphere; Irradiation; | 3.3. General Procedure B: Coupling of N-Hydroxyphthalimide Esters with Heterocycles 3, 5-18 General procedure: A 10 mL vial equipped with a stirrer bar and a septum was flushed with argon and charged withdry N,N’-dimethylformamid. The solvent was previously degassed by ultrasonication (see GerneralInformation). The N-hydroxyphthalimide ester (0.30 mmol, 1.50 equiv.), the heterocyclic compound(0.20 mmol, 1 equiv.), p-toluenesulfonic acid monohydrate (0.30 mmol, 1.50 equiv.) and Ru(bpy)3Cl2(2 mol, 1 mol %) were added, followed by argon sparging for 1 min. The mixture was irradiated witha blue LED module from a distance of 5 cm for 48 h. A saturated aqueous NaHCO3 solution (30 mL)was added, followed by extraction with dichloromethane (3 x 15 mL). The combined organic layers were dried over MgSO4 and concentrated under reduced pressure. Flash column chromatographyafforded the desired product. |
| 97% | With potassium 1H-indole dithiocarbamate; trifluorormethanesulfonic acid In dimethyl sulfoxide at 40℃; for 24h; Inert atmosphere; Irradiation; | |
| 90% | With [Ir(dF(CF3)ppy)2(dtbbpy)]PF6; trifluoroacetic acid In N,N-dimethyl acetamide at 20℃; for 5h; Irradiation; Inert atmosphere; Electrochemical reaction; |
| 88% | With tetrakis(actonitrile)copper(I) hexafluorophosphate; 2,9-dimethyl-1,10-phenantroline; zinc trifluoromethanesulfonate; Xantphos In N,N-dimethyl acetamide for 24h; Inert atmosphere; Irradiation; | |
| 85% | With trifluoroacetic acid at 20℃; for 24h; Inert atmosphere; Irradiation; | |
| 84% | With triphenylphosphine; trifluoroacetic acid; sodium iodide In acetone at 20℃; for 15h; Irradiation; | |
| 81% | With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate; trifluoroacetic acid In N,N-dimethyl-formamide at 20℃; for 16h; Inert atmosphere; Glovebox; Sealed tube; Irradiation; | |
| 35% | With tetrabutylammonium tetrafluoroborate; toluene-4-sulfonic acid In N,N-dimethyl acetamide at 20℃; for 2.5h; Inert atmosphere; Electrochemical reaction; | |
| 41 mg | With 4CzIPN; trifluoroacetic acid In dimethyl sulfoxide at 40 - 48℃; for 3h; Irradiation; Sealed tube; Inert atmosphere; |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With palladium 10% on activated carbon; hydrogen; In ethanol; at 20℃; under 760.051 Torr; | 1-chloro-4-fluoroisoquinoline (9a) obtained by the method of Example 3(55 mg) in ethanol (2 mL)10percent Pd charcoal (26 mg; containing 54percent moisture) was added,Under 1 atm hydrogen atmosphere at room temperature until reductive cracking is complete (5 to 15 h)Followed by stirring. The catalyst was removed by filtration, and the filtrate was concentrated under reduced pressure.The residue was dissolved in ethyl acetate-water to remove the aqueous layer, the organic layer was washed with 20percent brine, and dried over anhydrous magnesium sulfate.The solvent was distilled off under reduced pressure to give 4-fluoroisoquinoline (1)And isoquinoline (33 mg) as a colorless oil. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 45% | With trichloroisocyanuric acid; sulfuric acid; at 0 - 10℃; for 24h; | To mechanically stirred concd H 2 SO 4 (100 mL), isoquinoline (1; 12.9 g,0.1 mol, 1.0 equiv) was slowly added at 0 C. During intensive stirringTCCA (12.8 g, 55 mmol, 1.65 equiv) was then added in 4 portionswhile the reaction temperature was kept at 10 C. The mixture wasthen stirred at 10 C and followed by GC-MS. After 24 h the reactionmixture was poured onto crushed ice (ca. 200 g) and the precipitatewas filtered. The pH of the filtrate was adjusted to 2 with concd aqNH 3 solution with extensive cooling. The slurry was then filtered. Thefiltrate was extracted with toluene (6 × 75 mL) to remove the sideproduct, 5,8-dichloroisoquinoline (16). The aqueous phase was fur-ther basified with concd aq NH 3 solution until pH 6 was reached. Atthis point the precipitate was filtered, washed with H 2 O, and dried inair. Finally, the filtrate was recrystallized from methylcyclohexane toafford 15.Yield: 7.60 g (45%); mp 70-72 C.IR (ATR): 1580, 1489, 1371, 1267, 1204, 1140, 1065, 984, 822, 750,687, 628, 536 cm -1 .1 H NMR (400 MHz, CDCl 3 ): δ = 9.27 (s, 1 H), 8.64 (d, J = 6.0 Hz, 1 H),8.02 (d, J = 6.0 Hz, 1 H), 7.90 (d, J = 8.2 Hz, 1 H), 7.77 (d, J = 7.5 Hz, 1 H),7.53 (t, J = 7.8 Hz, 1 H).13 C NMR (100 MHz, CDCl 3 ): δ = 152.4, 143.9, 133.7, 131.0, 130.3,129.4, 127.3, 126.7, 116.9. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 72% | With diphenyl hydrogen phosphate; 9-mesityl-10-methylacridinium perchlorate In 1,2-dichloro-ethane at 60℃; for 48h; Irradiation; Flow reactor; | |
| 70% | With ammonium peroxydisulfate; chloro-trimethyl-silane; 1,1,1-trichloroethanol; trifluoroacetic acid In acetonitrile at 12℃; for 18h; High pressure; Irradiation; regioselective reaction; | |
| 62% | With ammonium peroxydisulfate; cerium(IV) sulphate; 1,1,1-trichloroethanol; sulfuric acid; tetrabutyl-ammonium chloride In acetonitrile at 20℃; Irradiation; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 68% | With tert.-butylhydroperoxide; iron(III) perchlorate hydrate In water at 100℃; for 12h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 76% | With Selectfluor; trifluoroacetic acid In acetonitrile at 25℃; for 24h; Schlenk technique; Inert atmosphere; Irradiation; regioselective reaction; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Stage #1: isoquinoline; dimethyl sulfate In neat (no solvent) at 110℃; for 1.5h; Stage #2: With formic acid; triethylamine at 110℃; | Synthesis of 2-(N,N-dialkyl)aminomethylstyrenes 4. General procedure: A mixture of isoquinoline 10.0g (0.078 mol) and the corresponding alkyl halide or dialkyl sulfate (R1X = BnCl,Me2SO4, Et2SO4, 0.078 mol) was heated in a two-necked round-bottomed flask at110 °C under continuous stirring for 1.5 h. After that, formic acid 12.0 mL (14.8 g,0.326 mol) and triethylamine 12.0 mL (8.6 g, 0.086 mol) were added to the reactionmixture cooled to rt Then stirring and heating at 110 °C were continued for another 4-6 h until gas evolution ceased (a bubble counter was used). After cooling of thereaction mixture to rt, ≈60 mL of 20% NaOH solution (14.0 g, 0.32 mol of NaOH in 56mL of H2O) was added. The solution was stirred at rt for 15 min, diluted with Et2O (50mL), and stirred for another 15 min. The organic layer was separated and the waterphase was extracted with Et2O (50 mL). The combined organic phases were washedwith water (2 × 50 mL), dried over MgSO4 and filtered. The target N-alkyl-1,2,3,4-tetrahydroisoquinolines 3 were obtained as viscous, dark-brown oils after evaporation of the solvents under reduced pressure. These crude products weredirected to the next alkylation stage without further purification assuming 100% yield.A mixture of N-alkyl-1,2,3,4-tetrahydroisoquinoline (3, ≈0.078 mol) and thecorresponding alkyl halide or dialkyl sulfate (R2X, see Table 1, 0.078 mol) washeated at 110 °C and continuous stirring for 1.5 h in a two-necked round-bottomedflask. After cooling of the reaction mixture to rt, iPrOH (40 mL) and NaOH 6.40 g(0.16 mol) were added, then stirring and heating at 85 °C were continued for anotherhour. The solvent was evaporated under reduced pressure, then a mixture of H2O(60 mL) and Et2O (80 mL) was added, and the reaction mixture was stirred foradditional 30 min at rt. The organic layer was separated and the water phase was extracted with Et2O (80 mL). The combined organic phases were filtered throughsilica gel (4 × 3 cm), the sorbent was washed with Et2O (2 × 50 mL).After evaporation of the solvent under reduced pressure, crude 2-(N,Ndialkyl)aminomethylstyrenes (4) were obtained as viscous brown or dark-yellow oils.The analytical samples for analysis and catalysts synthesis were obtained afterpurification of the crude products by silica gel column chromatography using hexaneas an eluent, which gives target styrenes 4 as slightly yellow or colorless, viscousoils, in 60-88 % yields after four steps, see Table 1. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 82% | With trifluoroacetic acid at 20℃; for 24h; Inert atmosphere; Irradiation; | |
| 61% | With tetrakis(actonitrile)copper(I) hexafluorophosphate; 2.9-dimethyl-1,10-phenanthroline; zinc trifluoromethanesulfonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In N,N-dimethyl acetamide for 24h; Inert atmosphere; Irradiation; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 82% | With dipotassium peroxodisulfate; (4,4'-di-tert-butyl-2,2'-dipyridyl)-bis-(2-phenylpyridine(-1H))-iridium(III) hexafluorophosphate; trifluoroacetic acid In acetonitrile at 20℃; for 16h; Irradiation; Inert atmosphere; | |
| 49 % | With trifluoroacetic acid In acetonitrile at 20℃; Irradiation; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Stage #1: isoquinoline; N-hydroxymethyl trifluoroacetamide In sulfuric acid at 0℃; for 0.25h; Stage #2: at 20℃; for 16h; | 4 Isoquinoline 4-1 (0.01 mole, 1.29 g) was dissolved in 50 mL of concentrated H2SO4 (sulfuric acid) which had been cooled to 0° C. in an ice-water bath. The N-hydroxymethyl trifluoroacetamide was then added in portions. The reaction mixture was stirred at 0° C. for 15 minutes and then allowed to warm to room temperature and stirred for 16 hours. The clear light brown reaction mixture was poured onto 200 g of ice then NH4OH (ammonium hydroxide) was added until the reaction mixture was basic to pH paper. The aqueous mixture was extracted with 100 mL of CH2Cl2 (methylene chloride). The organic layer was separated and washed with 2×100 mL of brine, dried over Na2SO4 (sodium sulfate) and evaporated in vacuo. The residue was chromatographed on silica gel eluting with 60/40 hexane/ethyl acetate to yield the trifluoroacetamide 4-2 product as a white crystalline solid (0.008 mole, 2.03 g). MS (MH+): 255; 1H NMR (CDCl3): δ 5.0 (s, 2H), 7.6 (t, 1H), 7.8 (d, 1H), 7.95 (d, 1H), 8.1 (d, 1H), 8.5 (d, 1H), 9.2 (s, 1H). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 66% | With acetic acid In 1,2-dichloro-ethane; chlorobenzene at 140℃; for 20h; Autoclave; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 86% | With (tBuPNN)Ru(CO)HCl; water; hydrogen; potassium hydroxide In 1,4-dioxane at 150℃; for 72h; Inert atmosphere; | General procedure for the synthesis of 2a-2x and 2ae-2ah General procedure: In a N2 glovebox, Ru-1 (3.6mg, 1.5mol%), KOH (5.6mg, 0.1mmol),N-heteroarene (0.5mmol), H2O (1ml) and dioxane (1ml) were addedto an 80ml Fisher-Porter tube (with an internal Teflon tube; SupplementaryInformation). The tube was removed from the glovebox and pressurized with 0.5bar H2 (exceptions indicated in Fig. 3). The mixturewas heated in an oil bath at 150°C for 3-5days. After cooling to roomtemperature, hydrogen gas was released. The mixture was neutralizedwith HCl (1M) to pH7.0 and then extracted three times with EtOAc.The combined organic solution was dried over Na2SO4, filtered andconcentrated under reduced pressure. The residue was purified bycolumn chromatography using a flash silica gel column. |
| Multi-step reaction with 3 steps 1: tris(pentafluorophenyl)borate / chloroform-d1 / 8 h / 20 - 110 °C / Inert atmosphere 2: chloroform-d1 / 2 h / 0 - 20 °C / Inert atmosphere 3: hydrogenchloride / water; methanol / 5 h / 20 - 85 °C / Inert atmosphere |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 96% | Stage #1: dichlorotetrakis(dimethyl sulfoxide)ruthenium(II); 2-(2-hydroxy-5-(trifluoromethyl)phenyl)-1H-benzo[d]imidazole-4-carboxylic acid With triethylamine In methanol at 60℃; for 3h; Sonication; Stage #2: isoquinoline In methanol at 60℃; for 5h; Sonication; | Synthesis complexes (5 and 9) General procedure: Ligands 4 and 8 (0.5 mmol) and Et3N (0.6 mL, 4.3 mmol) were dissolved inMeOH (3.0 mL). To this solution, [Ru(DMSO)4Cl2] (242 mg, 0.5 mmol) wasadded and the reaction mixture was sonicated for 3 h at 60 oC. Then 4-picoline (1.2mL, 12.0 mmol) (or isoquinoline in case of 5b) was added, and the mixture wasfurther sonicated for 5 h at 60 oC. The addition of H2O (3.0 mL) gave a darkprecipitate. The precipitate was isolated by centrifugation, washed with water (5 x10.0 mL) then Et2O (3 x 10.0 mL), and dried under vacuum to afford a dark redsolid. The crude product was purified by automated flash chromatography on asilica column (MeCN/MeOH as eluent, 0% to 10% gradient of MeOH). Thefractions containing the desired product were combined, concentrated underreduced pressure and evacuated to afford the desired complexes 5 and 9 as dark redcrystals. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 54% | With ethanol; bis-[(trifluoroacetoxy)iodo]benzene In dimethyl sulfoxide; 1,2-dichloro-ethane at 20℃; for 12h; Schlenk technique; Inert atmosphere; Irradiation; diastereoselective reaction; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 55% | In ethanol; water at 65℃; Inert atmosphere; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 59% | With oxygen; toluene-4-sulfonic acid; copper dichloride In N,N-dimethyl-formamide at 120℃; for 12h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 89% | With sodium persulfate; trifluoroacetic acid In dimethyl sulfoxide at 60℃; for 24h; Inert atmosphere; Sealed tube; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 35% | With TEMPOL; boron carbonitride In water; 1,2-dichloro-ethane at 25℃; for 60h; Irradiation; Inert atmosphere; Green chemistry; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 4 steps 1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 20 °C / Cooling with ice 2: trichlorophosphate / chloroform / Reflux 3: sulfuric acid; nitric acid / water / 0 °C 4: acetic acid / 100 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 27% | With sulfuric acid at 0 - 20℃; for 16.25h; Inert atmosphere; | 56.1 Step 1: 2,2,2-Trifluoro-N-(isoquinolm-5-ylmethyl)acetamide (56.3) [00566] Intermediate 56.2 (1.43 g, 10.00 mmol) was added portion wise to a stirred solution of intermediate 56.1 (1.29 g, 10.00 mmol) in cone. H2SO4 (50 mL) cooled at 0-5 °C. Stirring was continued at 0-5 °C for 15 min, then the reaction was allowed to warm to r.t. and stirred for further 16 h. The mixture was cautiously poured into stirred ice (200 g), ammonia 28% (130 mL) was then added dropwise until a basic pH was reached. The aqueous mixture was extracted with CH2CI2 (3 x 20 mL), the collected organic layers were washed with brine (40 mL), dried over Na2SC>4, and concentrated under reduced pressure. After chromatographic purification (PET/EtOAc from 90:10 to 40:60), 0.68 g of intermediate 56.3 were obtained. Yield: 27% [00567] MS-ESI(+) m/z: 255.3 (M+H). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 87% | With choline peroxydisulfate In water monomer at 40℃; for 24h; Sealed tube; | |
| With anthracen-9(10H)-one; trifluoroacetic acid In 1,2-dichloro-ethane at 25℃; Irradiation; | 3. General procedure for acylation of N-heterocycles General procedure: A 5-mL screw-capped reaction tube equipped with a magnetic stir bar was filled with anthrone (0.06 mmol, 0.3 equiv.), α-keto acid (0.60 mmol, 3 equiv.) TFA(0.02mmol,0.1 equiv) and N-heterocycle (0.20 mmol, 1 equiv.), followed by the addition of 1,2-dichloroethane(1.0 mL) under air. Then, the reaction tube was placed approximately 2 cm away from each 8×5W Violet bulbs (see picture of the reaction set-up). The reaction mixture was allowed to stir at room temperature and irradiated with 8×5 W Violet bulbs for 12 hours (vial temperature reached 45 °C).The reaction mixture became darker and a color change from slight yellow to orange/brown was generally observed after the transformation (see pictures of the reaction mixtures). After opening of the reaction tube, off-gassing was observed. Subsequently, the solution was diluted with DCM (10 mL), washed with an aqueous saturated solution of NaHCO3 (10 mL) and extracted with DCM (2 ×10 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered off and concentrated under reduced pressure to afford the crude product. The crude product was purified by column chromatography on silica gel to provide the desired compound. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 73% | In acetonitrile at 25℃; for 1h; Inert atmosphere; diastereoselective reaction; | 4.3. General procedure for the synthesis of the dialkyl 2-1-(diarylphosphoryl)isoquinolin-2(1H)-yl)maleate derivatives (9-12) General procedure: To a solution of 1.0 mmol secondary phosphine oxide (0.30 g di(naphthalen-2-yl)phosphine oxide, 0.23 g of dibenzylphosphine oxide) and 4 mL of MeCN, 1.2 mmol (0.14 mL) of isoquinoline and 1.2 mmol of dialkyl acetylenedicarboxylate (0.19 mL diethyl acetylenedicarboxylate or 0.15 mL dimethyl acetylenedicarboxylate) were added under nitrogen atmosphere. The reaction mixture was stirred at 25 °C for 60 min. After the reaction was complete, the solvent was removed under reduced pressure. The products were purified by column chromatography using silica gel as the solid phase and ethyl acetate: n-hexane 1:1 as eluent. |
| 73% | In acetonitrile at 25℃; for 1h; Inert atmosphere; diastereoselective reaction; | 4.3. General procedure for the synthesis of the dialkyl 2-1-(diarylphosphoryl)isoquinolin-2(1H)-yl)maleate derivatives (9-12) General procedure: To a solution of 1.0 mmol secondary phosphine oxide (0.30 g di(naphthalen-2-yl)phosphine oxide, 0.23 g of dibenzylphosphine oxide) and 4 mL of MeCN, 1.2 mmol (0.14 mL) of isoquinoline and 1.2 mmol of dialkyl acetylenedicarboxylate (0.19 mL diethyl acetylenedicarboxylate or 0.15 mL dimethyl acetylenedicarboxylate) were added under nitrogen atmosphere. The reaction mixture was stirred at 25 °C for 60 min. After the reaction was complete, the solvent was removed under reduced pressure. The products were purified by column chromatography using silica gel as the solid phase and ethyl acetate: n-hexane 1:1 as eluent. |
| In acetonitrile at 25℃; Inert atmosphere; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With anthracen-9(10H)-one; trifluoroacetic acid In 1,2-dichloro-ethane at 25℃; Irradiation; | 3. General procedure for acylation of N-heterocycles General procedure: A 5-mL screw-capped reaction tube equipped with a magnetic stir bar was filled with anthrone (0.06 mmol, 0.3 equiv.), α-keto acid (0.60 mmol, 3 equiv.) TFA(0.02mmol,0.1 equiv) and N-heterocycle (0.20 mmol, 1 equiv.), followed by the addition of 1,2-dichloroethane(1.0 mL) under air. Then, the reaction tube was placed approximately 2 cm away from each 8×5W Violet bulbs (see picture of the reaction set-up). The reaction mixture was allowed to stir at room temperature and irradiated with 8×5 W Violet bulbs for 12 hours (vial temperature reached 45 °C).The reaction mixture became darker and a color change from slight yellow to orange/brown was generally observed after the transformation (see pictures of the reaction mixtures). After opening of the reaction tube, off-gassing was observed. Subsequently, the solution was diluted with DCM (10 mL), washed with an aqueous saturated solution of NaHCO3 (10 mL) and extracted with DCM (2 ×10 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered off and concentrated under reduced pressure to afford the crude product. The crude product was purified by column chromatography on silica gel to provide the desired compound. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Stage #1: isoquinoline; ethynylmagnesium bromide In tetrahydrofuran at 20 - 60℃; for 10.16h; Inert atmosphere; Stage #2: With 5%-palladium/activated carbon at 50℃; for 20h; | 3 Preparation of 1-ethylisoquinoline mixture Under nitrogen protection, add to a 250ml four-neck bottle46.5ml of a commercially available 1.0M solution of ethylmagnesium bromide in THF (2.0eq),3.0 g of isoquinoline (1.0 eq) was added, stirred at room temperature for 10 min, heated to 60° C., and incubated for 10 h.The content detected by gas chromatography is as follows: 1-ethylisoquinoline 60%,1-Ethyl-1,2-dihydroisoquinoline 25%,1-Ethyl-1,2,3,4-tetrahydroisoquinoline 3%.Under nitrogen protection, the reaction system was cooled to 0° C., 30 ml of methyl tert-butyl ether was added, and 3 g of 20% ammonium chloride aqueous solution was added dropwise to quench the reaction, and the aqueous phase was separated.0.3 g of commercially available 5% palladium carbon was added to the organic phase, and the temperature was raised to 50° C. again and stirred for 10 h.Detected content by gas chromatography, 1-ethylisoquinoline was 80%. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 46 % | With (4,4'-di-tert-butyl-2,2'-dipyridyl)-bis-(2-phenylpyridine(-1H))-iridium(III) hexafluorophosphate In N,N-dimethyl acetamide at 20℃; Irradiation; Inert atmosphere; Sealed tube; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 86 % | With (4,4'-di-tert-butyl-2,2'-dipyridyl)-bis-(2-phenylpyridine(-1H))-iridium(III) hexafluorophosphate In N,N-dimethyl acetamide at 20℃; Irradiation; Inert atmosphere; Sealed tube; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 73 % | With copper(I) oxide In 1,2-dimethoxyethane at 85℃; | General procedure for the synthesis of 4 General procedure: Isoquinoline 1a (0.6mmol), bromoester 2 (0.3 mmol), alkenoic acid 3 (0.2 mmol) and Cu2O(0.4 mmol) were firstly mixed in 6 mL of DME and then heated at 85 °C in oil bath for 16 h in a 50 mL round bottle. After completion of the reaction, the mixture was cooled to room temperature and separated by flash column chromatography to afford 4. For products 4d and 4e, the reaction temperature was lowered to 75 °C and the heating time was prolonged to 24 h. For products 4f and 4g, the temperature was raised to100 °C and the round bottle was changed to a 50 mL sealed tube. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 71 % | With copper(I) oxide In 1,2-dimethoxyethane at 85℃; | General procedure for the synthesis of 4 General procedure: Isoquinoline 1a (0.6mmol), bromoester 2 (0.3 mmol), alkenoic acid 3 (0.2 mmol) and Cu2O(0.4 mmol) were firstly mixed in 6 mL of DME and then heated at 85 °C in oil bath for 16 h in a 50 mL round bottle. After completion of the reaction, the mixture was cooled to room temperature and separated by flash column chromatography to afford 4. For products 4d and 4e, the reaction temperature was lowered to 75 °C and the heating time was prolonged to 24 h. For products 4f and 4g, the temperature was raised to100 °C and the round bottle was changed to a 50 mL sealed tube. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 70 % | With copper(I) oxide In 1,2-dimethoxyethane at 85℃; | General procedure for the synthesis of 4 General procedure: Isoquinoline 1a (0.6mmol), bromoester 2 (0.3 mmol), alkenoic acid 3 (0.2 mmol) and Cu2O(0.4 mmol) were firstly mixed in 6 mL of DME and then heated at 85 °C in oil bath for 16 h in a 50 mL round bottle. After completion of the reaction, the mixture was cooled to room temperature and separated by flash column chromatography to afford 4. For products 4d and 4e, the reaction temperature was lowered to 75 °C and the heating time was prolonged to 24 h. For products 4f and 4g, the temperature was raised to100 °C and the round bottle was changed to a 50 mL sealed tube. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 51 % | With copper(I) oxide In 1,2-dimethoxyethane at 100℃; Sealed tube; | General procedure for the synthesis of 4 General procedure: Isoquinoline 1a (0.6mmol), bromoester 2 (0.3 mmol), alkenoic acid 3 (0.2 mmol) and Cu2O(0.4 mmol) were firstly mixed in 6 mL of DME and then heated at 85 °C in oil bath for 16 h in a 50 mL round bottle. After completion of the reaction, the mixture was cooled to room temperature and separated by flash column chromatography to afford 4. For products 4d and 4e, the reaction temperature was lowered to 75 °C and the heating time was prolonged to 24 h. For products 4f and 4g, the temperature was raised to100 °C and the round bottle was changed to a 50 mL sealed tube. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 87% | In ethyl acetate at 80℃; for 12h; Sealed tube; | General procedure for the synthesis of compounds3a-3o. General procedure: To a sealed tube, chloroacetamide (0.3 mmol) andisoquinoline (0.3 mmol) were added, followed by theaddition of 1 mL ofl ethyl acetate. The reaction mixturewas then stirred at 80°C for 12 h. Water (8 mL) was addedto the reaction solution, and the mixture was extractedwith dichloromethane (4 × 5 mL). A pure target productcan be obtained by freeze-drying the aqueous solution toremove the water. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 65% | In dichloromethane at 120℃; for 12h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 63% | With dipotassium peroxodisulfate; potassium carbonate In acetonitrile at 50℃; for 12h; |
Tags: Isoquinoline | pyridine | cancer | MDR | multidrug-resistant | anti-cancer | 119-65-3 |
Precautionary Statements-General | |
| Code | Phrase |
| P101 | If medical advice is needed,have product container or label at hand. |
| P102 | Keep out of reach of children. |
| P103 | Read label before use |
Prevention | |
| Code | Phrase |
| P201 | Obtain special instructions before use. |
| P202 | Do not handle until all safety precautions have been read and understood. |
| P210 | Keep away from heat/sparks/open flames/hot surfaces. - No smoking. |
| P211 | Do not spray on an open flame or other ignition source. |
| P220 | Keep/Store away from clothing/combustible materials. |
| P221 | Take any precaution to avoid mixing with combustibles |
| P222 | Do not allow contact with air. |
| P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
| P230 | Keep wetted |
| P231 | Handle under inert gas. |
| P232 | Protect from moisture. |
| P233 | Keep container tightly closed. |
| P234 | Keep only in original container. |
| P235 | Keep cool |
| P240 | Ground/bond container and receiving equipment. |
| P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
| P242 | Use only non-sparking tools. |
| P243 | Take precautionary measures against static discharge. |
| P244 | Keep reduction valves free from grease and oil. |
| P250 | Do not subject to grinding/shock/friction. |
| P251 | Pressurized container: Do not pierce or burn, even after use. |
| P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
| P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
| P262 | Do not get in eyes, on skin, or on clothing. |
| P263 | Avoid contact during pregnancy/while nursing. |
| P264 | Wash hands thoroughly after handling. |
| P265 | Wash skin thouroughly after handling. |
| P270 | Do not eat, drink or smoke when using this product. |
| P271 | Use only outdoors or in a well-ventilated area. |
| P272 | Contaminated work clothing should not be allowed out of the workplace. |
| P273 | Avoid release to the environment. |
| P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
| P281 | Use personal protective equipment as required. |
| P282 | Wear cold insulating gloves/face shield/eye protection. |
| P283 | Wear fire/flame resistant/retardant clothing. |
| P284 | Wear respiratory protection. |
| P285 | In case of inadequate ventilation wear respiratory protection. |
| P231 + P232 | Handle under inert gas. Protect from moisture. |
| P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
| Code | Phrase |
| P301 | IF SWALLOWED: |
| P304 | IF INHALED: |
| P305 | IF IN EYES: |
| P306 | IF ON CLOTHING: |
| P307 | IF exposed: |
| P308 | IF exposed or concerned: |
| P309 | IF exposed or if you feel unwell: |
| P310 | Immediately call a POISON CENTER or doctor/physician. |
| P311 | Call a POISON CENTER or doctor/physician. |
| P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
| P313 | Get medical advice/attention. |
| P314 | Get medical advice/attention if you feel unwell. |
| P315 | Get immediate medical advice/attention. |
| P320 | |
| P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
| P321 | |
| P322 | |
| P330 | Rinse mouth. |
| P331 | Do NOT induce vomiting. |
| P332 | IF SKIN irritation occurs: |
| P333 | If skin irritation or rash occurs: |
| P334 | Immerse in cool water/wrap n wet bandages. |
| P335 | Brush off loose particles from skin. |
| P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
| P337 | If eye irritation persists: |
| P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
| P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
| P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
| P342 | If experiencing respiratory symptoms: |
| P350 | Gently wash with plenty of soap and water. |
| P351 | Rinse cautiously with water for several minutes. |
| P352 | Wash with plenty of soap and water. |
| P353 | Rinse skin with water/shower. |
| P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
| P361 | Remove/Take off immediately all contaminated clothing. |
| P362 | Take off contaminated clothing and wash before reuse. |
| P363 | Wash contaminated clothing before reuse. |
| P370 | In case of fire: |
| P371 | In case of major fire and large quantities: |
| P372 | Explosion risk in case of fire. |
| P373 | DO NOT fight fire when fire reaches explosives. |
| P374 | Fight fire with normal precautions from a reasonable distance. |
| P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
| P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
| P378 | |
| P380 | Evacuate area. |
| P381 | Eliminate all ignition sources if safe to do so. |
| P390 | Absorb spillage to prevent material damage. |
| P391 | Collect spillage. Hazardous to the aquatic environment |
| P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
| P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
| P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
| P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
| P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
| P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
| P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
| P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
| P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
| P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
| P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
| P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
| P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
| P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
| P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
| P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
| P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
| P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
| P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
| P370 + P376 | In case of fire: Stop leak if safe to Do so. |
| P370 + P378 | In case of fire: |
| P370 + P380 | In case of fire: Evacuate area. |
| P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
| P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
| Code | Phrase |
| P401 | |
| P402 | Store in a dry place. |
| P403 | Store in a well-ventilated place. |
| P404 | Store in a closed container. |
| P405 | Store locked up. |
| P406 | Store in corrosive resistant/ container with a resistant inner liner. |
| P407 | Maintain air gap between stacks/pallets. |
| P410 | Protect from sunlight. |
| P411 | |
| P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
| P413 | |
| P420 | Store away from other materials. |
| P422 | |
| P402 + P404 | Store in a dry place. Store in a closed container. |
| P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
| P403 + P235 | Store in a well-ventilated place. Keep cool. |
| P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
| P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
| P411 + P235 | Keep cool. |
Disposal | |
| Code | Phrase |
| P501 | Dispose of contents/container to ... |
| P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
| Code | Phrase |
| H200 | Unstable explosive |
| H201 | Explosive; mass explosion hazard |
| H202 | Explosive; severe projection hazard |
| H203 | Explosive; fire, blast or projection hazard |
| H204 | Fire or projection hazard |
| H205 | May mass explode in fire |
| H220 | Extremely flammable gas |
| H221 | Flammable gas |
| H222 | Extremely flammable aerosol |
| H223 | Flammable aerosol |
| H224 | Extremely flammable liquid and vapour |
| H225 | Highly flammable liquid and vapour |
| H226 | Flammable liquid and vapour |
| H227 | Combustible liquid |
| H228 | Flammable solid |
| H229 | Pressurized container: may burst if heated |
| H230 | May react explosively even in the absence of air |
| H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
| H240 | Heating may cause an explosion |
| H241 | Heating may cause a fire or explosion |
| H242 | Heating may cause a fire |
| H250 | Catches fire spontaneously if exposed to air |
| H251 | Self-heating; may catch fire |
| H252 | Self-heating in large quantities; may catch fire |
| H260 | In contact with water releases flammable gases which may ignite spontaneously |
| H261 | In contact with water releases flammable gas |
| H270 | May cause or intensify fire; oxidizer |
| H271 | May cause fire or explosion; strong oxidizer |
| H272 | May intensify fire; oxidizer |
| H280 | Contains gas under pressure; may explode if heated |
| H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
| H290 | May be corrosive to metals |
Health hazards | |
| Code | Phrase |
| H300 | Fatal if swallowed |
| H301 | Toxic if swallowed |
| H302 | Harmful if swallowed |
| H303 | May be harmful if swallowed |
| H304 | May be fatal if swallowed and enters airways |
| H305 | May be harmful if swallowed and enters airways |
| H310 | Fatal in contact with skin |
| H311 | Toxic in contact with skin |
| H312 | Harmful in contact with skin |
| H313 | May be harmful in contact with skin |
| H314 | Causes severe skin burns and eye damage |
| H315 | Causes skin irritation |
| H316 | Causes mild skin irritation |
| H317 | May cause an allergic skin reaction |
| H318 | Causes serious eye damage |
| H319 | Causes serious eye irritation |
| H320 | Causes eye irritation |
| H330 | Fatal if inhaled |
| H331 | Toxic if inhaled |
| H332 | Harmful if inhaled |
| H333 | May be harmful if inhaled |
| H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
| H335 | May cause respiratory irritation |
| H336 | May cause drowsiness or dizziness |
| H340 | May cause genetic defects |
| H341 | Suspected of causing genetic defects |
| H350 | May cause cancer |
| H351 | Suspected of causing cancer |
| H360 | May damage fertility or the unborn child |
| H361 | Suspected of damaging fertility or the unborn child |
| H361d | Suspected of damaging the unborn child |
| H362 | May cause harm to breast-fed children |
| H370 | Causes damage to organs |
| H371 | May cause damage to organs |
| H372 | Causes damage to organs through prolonged or repeated exposure |
| H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
| Code | Phrase |
| H400 | Very toxic to aquatic life |
| H401 | Toxic to aquatic life |
| H402 | Harmful to aquatic life |
| H410 | Very toxic to aquatic life with long-lasting effects |
| H411 | Toxic to aquatic life with long-lasting effects |
| H412 | Harmful to aquatic life with long-lasting effects |
| H413 | May cause long-lasting harmful effects to aquatic life |
| H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
Home
* Country/Region
* Quantity Required :
* Cat. No.:
* CAS No :
* Product Name :
* Additional Information :
Total Compounds: mg
The concentration of the dissolution solution you need to prepare is mg/mL






