2328-12-3

Basic information

• Product Name: 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride
• Synonyms: TIMTEC-BB SBB003285;1,2,3,4-tetrahydro-6,7-dimethoxy-isoquinolinhydrochloride;1,2,3,4-TETRAHYDRO-6,7-DIMETHOXY-ISOQUINOLINE HYDROCHLORIDE;6,7-DIMETHOXY-1,2,3,4-TETRAHYDROISOQUINOLINE HYDROCHLORIDE;LABOTEST-BB LT00453025;ISOQUINOLINE, 1,2,3,4-TETRAHYDRO-6,7-DIMETHOXY-, HYDROCHLORIDE;6,7-Dimethoxy-1,2,3,4-tetrahyroisoquinoline hydrochloride, 97%;6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinolineHCl
• CAS NO: 2328-12-3
• Molecular Formula: C₁₁H₁₆NO₂*Cl
• Molecular Weight: 229.7
• EINECS: 251-223-7
• Product Categories: API intermediates;Building Blocks;Heterocyclic Building Blocks;Isoquinolines
• Mol File: 2328-12-3.mol
• Article Data: 11

Chemical Properties

• Melting Point: 260-265 °C(lit.)
• Boiling Point: 314.9 °C at 760 mmHg
• Flash Point: 124.7 °C
• Appearance: White to slightly beige/Shiny Flakes or Crystalline Powder
• Density: 1.071g/cm³
• Vapor Pressure: 0.000451mmHg at 25°C
• Storage Temp.: Store below +30°C.
• Solubility: soluble25mg/mL, clear, colorless (1N NaOH in methanol)
• BRN: 3634126
• CAS DataBase Reference: 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride(2328-12-3)
• EPA Substance Registry System: 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride(2328-12-3)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• RTECS: NX5017980
• HazardClass: IRRITANT
• Hazardous Substances Data: 2328-12-3(Hazardous Substances Data)

Usage

Chemical Properties

white to slightly beige shiny flakes or

Uses

6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride has been used as starting material for the synthesis of more complex isoquinolines and quinolizidines.

General Description

6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride is also referred as heliamine. It is an alkaloid isolated from mexican cereoid, Backebergia militaris.

InChI:InChI=1/C11H15NO2/c1-13-10-5-8-3-4-12-7-9(8)6-11(10)14-2/h5-6,12H,3-4,7H2,1-2H3/p+1

Synthetic route

Dimethoxymethane (109-87-5) + 2-(3,4-dimethoxyphenyl)-ethylamine (120-20-7) → 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride (2328-12-3)

Conditions	Yield
With hydrogenchloride In water for 8h; Heating;	88%

formaldehyd (50-00-0) + 2-(3,4-dimethoxyphenyl)-ethylamine (120-20-7) → 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride (2328-12-3)

Conditions	Yield
With hydrogenchloride In ethanol Pictet-Spengler reaction;	68.7%
Stage #1: formaldehyd; 2-(3,4-dimethoxyphenyl)-ethylamine In ethanol at 20℃; for 3h; Stage #2: With hydrogenchloride In ethanol; water for 4h; pH=2; Reflux;	61.8%
Stage #1: formaldehyd; 2-(3,4-dimethoxyphenyl)-ethylamine In ethanol at 20℃; for 3h; Stage #2: With hydrogenchloride In ethanol; water at 78℃; for 4h; pH=2;	61.8%

bis(N-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolinyl)methane (26259-07-4) → 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride (2328-12-3)

Conditions	Yield
With hydrogenchloride In water; isopropyl alcohol at 20℃; for 18h;

hydrogenchloride (7647-01-0) + C9H7(OCH3)2NBH3 (14429-07-3) → hydrogen (1333-74-0) + 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride (2328-12-3)

Conditions	Yield
In ethanol; water addn. of 5% aq. HCl to the ethanol soln. (cooling, stirring), stirring for 30min, refluxing for 30min;;

6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride (2328-12-3) → 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline hydrobromide (52768-23-7)

Conditions	Yield
With hydrogen bromide at 120℃; for 2h;	100%
With hydrogen bromide at 105℃; for 5h;	100%
With water; hydrogen bromide for 5h; Heating / reflux;	100%

6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride (2328-12-3) → 5,8-dichloro-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (860436-60-8)

Conditions	Yield
With sulfuryl dichloride In acetic acid at 20℃; for 3h;	100%
With sulfuryl dichloride In acetic acid at 20℃; for 3h;	100%
With sulfuryl dichloride In acetic acid at 20℃; for 4h;	100%
With sulfuryl dichloride; acetic acid at 20℃; for 3h;	100%
With sulfuryl dichloride In acetic acid at 20℃; for 0.5h; Product distribution / selectivity;

formaldehyd (50-00-0) + 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride (2328-12-3) → 2-methyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (16620-96-5)

Conditions	Yield
Stage #1: 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride With sodium hydroxide In methanol for 0.333333h; Stage #2: formaldehyd In methanol; water for 0.583333h; Stage #3: With sodium tetrahydroborate In methanol; water	100%
Stage #1: formaldehyd; 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride With sodium methylate In methanol; water for 0.916667h; Inert atmosphere; Stage #2: With sodium tetrahydroborate In methanol; water at 20℃; for 3h; Inert atmosphere;	90%
Stage #1: 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride With sodium hydroxide In dichloromethane; water Inert atmosphere; Stage #2: formaldehyd With formic acid In water at 100℃; Inert atmosphere;	80%

phosgene (75-44-5) + 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride (2328-12-3) → carbamic chloride (463-72-9)

Conditions	Yield
In toluene	99%

6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride (2328-12-3) + 5-bromo-2-furanyl chloride → 5-bromo-2-(2'-H-3,4-dihydro-6,7-methoxyisoquinoline)furan-2-carboxamide

Conditions	Yield
Stage #1: 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride With sodium hydroxide In dichloromethane; water at 0℃; for 0.5h; Stage #2: 5-bromo-2-furanyl chloride In dichloromethane at 0 - 25℃;	99%

3-chloro-1-(2,4-dimethoxyphenyl)acetone + 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride (2328-12-3) → 3-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl)-1-(2,4-dimethoxyphenyl)propan-1-one

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 6h;	97.7%

6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride (2328-12-3) + cyanomethyl bromide (590-17-0) → 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)acetonitrile (160446-14-0)

Conditions	Yield
With triethylamine In dichloromethane for 48h; Inert atmosphere;	97.3%
With triethylamine In dichloromethane at 50℃; for 12h;

Cyclohexyl isocyanide (931-53-3) + fluorenone imine (4440-33-9) + 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride (2328-12-3) → 1-(1-cyclohexyl-1H-tetrazol-5-yl)-2-(9H-fluoren-9-yl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline

Conditions	Yield
With trimethylsilylazide In methanol at 90℃; for 20h; Ugi Condensation; Inert atmosphere;	96%

5-bromo-furan-2-carboxylic acid (585-70-6) + 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride (2328-12-3) → 5-bromo-2-(2'-H-3,4-dihydro-6,7-methoxyisoquinoline)furan-2-carboxamide

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; for 24h; Inert atmosphere;	95%

C15H11N3O2 + 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride (2328-12-3) → (E)-1-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-3-(2-phenylimidazo[1,2-a]pyrimidin-3-yl)prop-2-en-1-one

Conditions	Yield
Stage #1: C15H11N3O2 With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 0℃; for 0.5h; Stage #2: 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride In N,N-dimethyl-formamide at 20℃; for 4h; Inert atmosphere;	94%

2-(3-bromopropyl)isoindole-1,3-dione (5460-29-7) + 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride (2328-12-3) → 2-[3-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-propyl]-isoindole-1,3-dione

Conditions	Yield
With potassium carbonate In DMF (N,N-dimethyl-formamide) at 20℃;	93%

trimethylacetic formic anhydride (10535-67-8) + 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride (2328-12-3) → 6,7-dimethoxy-3,4-dihydroisoquinoline-2(1H)-carbaldehyde (96624-17-8)

Conditions	Yield
Stage #1: trimethylacetic formic anhydride; 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride With triethylamine In dichloromethane at 0 - 20℃; for 1h; Stage #2: With hydrogenchloride In dichloromethane; water Stage #3: With sodium hydrogencarbonate In dichloromethane; water	92%

6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride (2328-12-3) + benzyl bromide (100-39-0) → C25H28NO2(1+)*Br(1-)

Conditions	Yield
With potassium carbonate In ethanol for 4h; Reflux;	92%

Pentafluoropyridine (700-16-3) + 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride (2328-12-3) → N-(2',3',5',6'-tetrafluoro-4'-pyridyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide at 100℃;	91%

6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride (2328-12-3) + N-(tert-butyloxycarbonyl)nipecotic acid (71381-75-4, 88495-54-9, 84358-12-3) → tert-butyl 3-[(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)carbonyl]piperidine-1-carboxylate (312738-60-6)

Conditions	Yield
With WSC*HCl; benzotriazol-1-ol; triethylamine In 1,2-dichloro-ethane at 20℃; for 4h;	91%

(4-nitrophenyl)ethyl bromide (5339-26-4) + 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride (2328-12-3) → 1,2,3,4-Tetrahydro-6,7-dimethoxy-2-[2-(4-nitrophenyl)ethyl]-isoquinoline (82925-01-7)

Conditions	Yield
With potassium carbonate; sodium iodide In N,N-dimethyl-formamide at 100℃; for 12h; Industry scale;	90%
With potassium carbonate; sodium iodide In N,N-dimethyl-formamide at 100℃; for 12h;	90%
With potassium carbonate In acetonitrile for 18h; Reflux;	90.57%

(1S)-(-)-camphanic chloride (39637-74-6) + 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride (2328-12-3) → (1S,4R)-1-(6,7-Dimethoxy-1,2,3,4-tetrahydro-2-isoquinolylcarbonyl)-4,7,7-trimethyl-2-oxa-bicyclo<2.2.1>-heptan-3-one (123279-28-7)

Conditions	Yield
With triethylamine In dichloromethane 1) 0 deg C, 15 min, 2) RT, 4 h;	90.4%

7-[(6-bromohexyl)oxy]-3,4-dimethyl-2H-chromen-2-one + 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride (2328-12-3) → 7-{[6-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)hexyl]oxy}-3,4-dimethyl-2H-chromen-2-one

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; potassium iodide In acetonitrile	89%

6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride (2328-12-3) + 1-phenyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid (98534-81-7) → N-(4-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-oyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (1044873-10-0)

Conditions	Yield
With dmap; benzotriazol-1-ol; caesium carbonate; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 70h;	86%

3,4-dimethoxybenzene-1-sulfonyl chloride (23095-31-0) + 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride (2328-12-3) → 2-(3,4-dimethoxybenzenesulfonyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline

Conditions	Yield
With triethylamine; sodium hydroxide In dichloromethane; water at 20℃; for 0.5h;	86%

6-bromo-1-hexanenitrile (6621-59-6) + 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride (2328-12-3) → 6-(3,4-dihydro-6,7-dimethoxyisoquinolin-2(1H)-yl)hexanenitrile (916993-88-9)

Conditions	Yield
With tetra-(n-butyl)ammonium iodide; potassium carbonate; potassium iodide In N,N-dimethyl-formamide for 16h;	86%

6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride (2328-12-3) + C26H22ClNO2S → N-benzyl-N-{4’-[(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl)methyl]-[1,1′-biphenyl]-4-yl}benzenesulfonamide

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 70℃; for 8h;	86%

6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride (2328-12-3) + cis-2-chloro-N-(3-methoxy-3H-spiro[[2]benzopyran-1,1’-cyclohexan]-4’-yl)acetamide → cis-2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-N-(3-methoxy-3H-spiro[[2]benzofuran-1,1’-cyclohexan]-4’-yl)acetamide

Conditions	Yield
With tetra-(n-butyl)ammonium iodide; triethylamine In N,N-dimethyl-formamide at 20℃; for 144h;	86%

6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride (2328-12-3) + 4-bromobutanenitrile (5332-06-9) → 4-(3,4-dihydro-6,7-dimethoxyisoquinolin-2(1H)-yl)butanenitrile (669067-79-2)

Conditions	Yield
With tetra-(n-butyl)ammonium iodide; potassium carbonate; potassium iodide In N,N-dimethyl-formamide for 16h;	85%
With triethylamine In dichloromethane Inert atmosphere;	74.3%

fluorenone imine (4440-33-9) + 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride (2328-12-3) + 2-(3-indolyl)ethyl isocyanide (100571-64-0) → 1-(1-(2-(1H-indol-3-yl)ethyl)-1H-tetrazol-5-yl)-2-(9H-fluoren-9-yl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline

Conditions	Yield
With trimethylsilylazide In methanol at 90℃; for 16h; Ugi Condensation; Inert atmosphere;	85%

6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride (2328-12-3) + C25H28ClNO2S → N-{4’-[(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl)methyl]-[1,1′-biphenyl]-4-yl}-N-hexylbenzenesulfonamide

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 70℃; for 8h;	84%

5-bromopentan-1-nitrile (5414-21-1) + 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride (2328-12-3) → 5-(3,4-dihydro-6,7-dimethoxyisoquinolin-2(1H)-yl)pentanenitrile (916993-87-8)

Conditions	Yield
With tetra-(n-butyl)ammonium iodide; potassium carbonate; potassium iodide In N,N-dimethyl-formamide for 16h;	83%

6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride (2328-12-3) + trans-2-chloro-N-(3-methoxy-3,4-dihydrospiro[[2]benzopyran-1,1’-cyclohexan]-4’-yl)acetamide → trans-2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-N-(3-methoxy-3,4-dihydrospiro[[2]benzopyran-1,1’-cyclohexan]-4’-yl)acetamide

Conditions	Yield
With tetra-(n-butyl)ammonium iodide; triethylamine In N,N-dimethyl-formamide at 20℃; for 68h;	83%

2-chloro-N-(3-methoxyphenyl)pyrimidine-5-carboxamide + 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride (2328-12-3) → 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-N-(3-methoxyphenyl)pyrimidine-5-carboxamide

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 8h;	82%

Upstream product

• 50-00-0 formaldehyd 
• 120-20-7 2-(3,4-dimethoxyphenyl)-ethylamine 
• 109-87-5 Dimethoxymethane 
• 7647-01-0 hydrogenchloride 
• 14429-07-3 C₉H₇(OCH₃)2NBH₃ 
• 26259-07-4 bis(N-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolinyl)methane 

Downstream Products

• 15248-39-2 6,7-dimethoxyisoquinoline 
• 3382-18-1 6,7-dimethoxy-3,4-dihydro-isoquinoline 
• 124525-62-8 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)benzaldehyde 
• 82925-01-7 1,2,3,4-Tetrahydro-6,7-dimethoxy-2-[2-(4-nitrophenyl)ethyl]-isoquinoline 
• 692733-13-4 C₂₁H₂₅NO₆ 

Relevant articles and documents

Design, synthesis, and antifungal activities in vitro of novel tetrahydroisoquinoline compounds based on the structure of lanosterol 14α-demethylase (CYP51) of fungi

Novel tetrahydroisoquinoline compounds were designed by coupling structure-based de novo design based on the structure of lanosterol 14α-demethylase (CYP51). The chemical synthesis and the antifungal activities in vitro of them were reported. The results exhibited that all of the lead compounds showed potent antifungal activities, in which compounds 6 and 7 had equal or stronger antifungal activities against five test fungi than that of fluconazole. The studies presented here provided the antifungal lead compounds. The affinity of the lead molecules for CYP51 was mainly attributed to their non-bonding interaction with the apoprotein, which was different from the azole antifungal agents.

Design, synthesis and biological evaluation of N-(4-(2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)phenyl)-4-oxo-3,4-dihydrophthalazine-1-carboxamide derivatives as novel P-glycoprotein inhibitors reversing multidrug resistance

The overexpression of P-glycoprotein plays an important role in the process of multidrug resistance (MDR). P-gp inhibitors are one of the effective strategies to reverse tumor MDR. Novel P-gp inhibitors with phthalazinone scaffolds were designed, synthesized and evaluated. Compound 26 was found to be the most promising for further study. Compound 26 possessed high potency (EC50 = 46.2 ± 3.5 nM) and low cytotoxicity.26 possessed high MDR reversal activity towards doxorubicin-resistant K56/A02 cells. Reversal fold (RF) value reach to 44.26. 26 also increased accumulation of doxorubicin (DOX or ADM) or other MDR-related anticancer drugs with different structures. In conclusion, compound 26 deserves more research for its good features as P-gp inhibitor.

Discovery of aromatic amides with triazole-core as potent reversal agents against P-glycoprotein-mediated multidrug resistance

P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) is a major impediment for clinical cancer therapy. 19 novel aromatic amides with triazole-core as MDR reversal agents were designed and synthesized via click chemistry to reverse MDR. Among them, compound 42 was identified as the most promising candidate with high potency (EC50 = 78.1 ± 5.4 nM), low cytotoxity (SI > 1282) and persistent duration in reversing doxorubicin (DOX) resistance in K562/A02 cells. 42 also enhanced the potency of other P-gp associated cytotoxic agents with different structures. In further study, remarkably increased intracellular accumulation of Rh123 and DOX in K562/A02 cells was achieved by compound 42, while CYP3A4 activity had no change by compound 42. These results indicate that compound 42 as a relatively safe modulator of P-gp-mediated MDR has good potential for further development.