14446-24-3

Basic information

• Product Name: 1,2,3,4-TETRAHYDRO-ISOQUINOLIN-6-OL
• Synonyms: 1,2,3,4-tetrahydro-6-isoquinolino;1,2,3,4-TETRAHYDRO-ISOQUINOLIN-6-OL;6-HYDROXY-1,2,3,4-TETRAHYDRO-ISOQUINOLINE;1,2,3,4-Tetrahydro-6-isoquinolinol;H90100;6-Isoquinolinol, 1,2,3,4-tetrahydro-;6-hydroxy-1,2,3,4-Tetrahydroisoquinoline HCl;4-tetrahydro-isoquinolin-6-ol
• CAS NO: 14446-24-3
• Molecular Formula: C₉H₁₁NO
• Molecular Weight: 149.19
• EINECS: -0
• Product Categories: API intermediates
• Mol File: 14446-24-3.mol
• Article Data: 8

Chemical Properties

• Melting Point: 192-193℃
• Boiling Point: 313.5 °C at 760 mmHg
• Flash Point: 169.5 °C
• Appearance: /Solid
• Density: 1.141 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.582
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• PKA: 9.30±0.20(Predicted)
• CAS DataBase Reference: 1,2,3,4-TETRAHYDRO-ISOQUINOLIN-6-OL(CAS DataBase Reference)
• NIST Chemistry Reference: 1,2,3,4-TETRAHYDRO-ISOQUINOLIN-6-OL(14446-24-3)
• EPA Substance Registry System: 1,2,3,4-TETRAHYDRO-ISOQUINOLIN-6-OL(14446-24-3)

Safety Data

• RTECS: NX5898000
• Hazardous Substances Data: 14446-24-3(Hazardous Substances Data)

Usage

Description

1,2,3,4-Tetrahydroisoquinolin-6-ol is an organic compound with the chemical formula C9H11NO. It is a pale yellow liquid and serves as a crucial chemical reagent in the field of organic synthesis. 1,2,3,4-TETRAHYDRO-ISOQUINOLIN-6-OL is known for its role in the preparation of various pharmaceutical agents, including androgen receptor modulators (SARMs), steroidmimetic, and chimeric microtubule disruptors.

Uses

Used in Pharmaceutical Industry:
1,2,3,4-Tetrahydroisoquinolin-6-ol is used as a chemical reagent for the synthesis of androgen receptor modulators (SARMs). These modulators are designed to selectively target androgen receptors in the body, offering potential therapeutic benefits for conditions related to muscle wasting, osteoporosis, and other androgen-dependent disorders.
1,2,3,4-Tetrahydroisoquinolin-6-ol is also used as a chemical reagent in the preparation of steroidmimetic compounds. Steroidmimetics are synthetic molecules that mimic the effects of steroid hormones, which can be utilized in the treatment of various medical conditions, such as inflammation, immune disorders, and hormonal imbalances.
Furthermore, 1,2,3,4-Tetrahydroisoquinolin-6-ol is employed in the synthesis of chimeric microtubule disruptors. These disruptors are designed to target and destabilize microtubules, which are essential components of the cellular cytoskeleton. By disrupting microtubule function, these compounds can inhibit cell division and proliferation, making them potential candidates for cancer therapy.

InChI:InChI=1/C9H11NO/c11-9-2-1-8-6-10-4-3-7(8)5-9/h1-2,5,10-11H,3-4,6H2

Synthetic route

6-methoxy-1,2,3,4-tetrahydro-isoquinoline (42923-77-3) → 6-hydroxy-1,2,3,4-tetrahydroisoquinoline (14446-24-3)

Conditions	Yield
With hydrogen bromide at 120℃; for 3h;	10%
With hydrogenchloride; water at 170℃;
With boron tribromide In methanol; dichloromethane

formaldehyd (50-00-0) + 3-hydroxyphenylethylamine hydrochloride (3458-98-8) → 6-hydroxy-1,2,3,4-tetrahydroisoquinoline (14446-24-3) + 1,2,3,4-tetrahydroisoquinoline-8-ol (32999-37-4)

Conditions	Yield
In water at 20℃;
In water at 20℃; Product distribution; Mechanism; other 3-hydroxyphenethylamines, other aldehydes; var. pH;

norfenefrine (536-21-0) → 6-hydroxy-1,2,3,4-tetrahydroisoquinoline (14446-24-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 50 percent / H2 / 10percent Pd/C / aq. HCl / 30 h / 775.7 - 1810.02 Torr 2: H2O / 20 °C / other 3-hydroxyphenethylamines, other aldehydes; var. pH View Scheme

2-(3-methoxyphenyl)-1-ethanamine (2039-67-0) → 6-hydroxy-1,2,3,4-tetrahydroisoquinoline (14446-24-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrochloric acid; water 2: hydrochloric acid; water / 170 °C View Scheme

6-hydroxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (63905-73-7) → 6-hydroxy-1,2,3,4-tetrahydroisoquinoline (14446-24-3)

Conditions	Yield
Stage #1: 6-hydroxy-1,2,3,4-tetrahydroisoquinoline hydrochloride With sodium hydroxide In 1,4-dioxane; water at -5℃; Stage #2: With hydrogenchloride In 1,4-dioxane; water pH=9;

6-hydroxy-3,4-dihydro-2H-isoquinolin-1-one (22245-98-3) → 6-hydroxy-1,2,3,4-tetrahydroisoquinoline (14446-24-3)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran for 12h; Inert atmosphere; Reflux;

C11H15NO3 → 6-hydroxy-1,2,3,4-tetrahydroisoquinoline (14446-24-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: trifluorormethanesulfonic acid / 16 h / 20 - 70 °C 2: lithium aluminium tetrahydride / tetrahydrofuran / 12 h / Inert atmosphere; Reflux View Scheme

m-tyramine (588-05-6) → 6-hydroxy-1,2,3,4-tetrahydroisoquinoline (14446-24-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 1 h / 0 - 25 °C 2: trifluorormethanesulfonic acid / 16 h / 20 - 70 °C 3: lithium aluminium tetrahydride / tetrahydrofuran / 12 h / Inert atmosphere; Reflux View Scheme

6-hydroxy-1,2,3,4-tetrahydroisoquinoline (14446-24-3) + di-tert-butyl dicarbonate (24424-99-5) → N-tert-butoxycarbonyl-6-hydroxy-1,2,3,4-tetrahydroisoquinoline (158984-83-9)

Conditions	Yield
With triethylamine In tetrahydrofuran; water at 20℃;	91%
With triethylamine In dichloromethane at 0 - 20℃; for 12h;	80%
With triethylamine In methanol at 20℃;	66%

6-hydroxy-1,2,3,4-tetrahydroisoquinoline (14446-24-3) + 6-aethoxycarbonyl-2-chlorbenzothiazol (78485-37-7) → ethyl 2-(6-hydroxy-3,4-dihydroisoquinolin-2(1H)-yl)benzo[d]thiazole-6-carboxylate

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 100℃; for 1h;	84%

6-hydroxy-1,2,3,4-tetrahydroisoquinoline (14446-24-3) + acryloyl chloride (814-68-6) → N-acryloyl-6-hydroxy-1,2,3,4-tetrahydroisoquinoline

Conditions	Yield
Stage #1: 6-hydroxy-1,2,3,4-tetrahydroisoquinoline With triethylamine In dichloromethane at 25℃; for 0.5h; Stage #2: acryloyl chloride In dichloromethane at 0 - 25℃;	79%

6-hydroxy-1,2,3,4-tetrahydroisoquinoline (14446-24-3) + toluene-4-sulfonic acid (104-15-4) → C9H9Cl2NO*C7H8O3S (1609545-55-2)

Conditions	Yield
With N-chloro-succinimide In acetonitrile at 20℃;	61%

6-hydroxy-1,2,3,4-tetrahydroisoquinoline (14446-24-3) + (2RS,4SR)-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-ylmethyl methanesulfonate (345649-43-6) + biphenyl-4-methylchloride (1667-11-4) → 6-[(2RS,4SR)-2-(2,4-Dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-ylmethyloxy]-2-(4-phenylbenzyl)-1,2,3,4-tetrahydroisoquinoline

Conditions	Yield
With potassium carbonate In N-methyl-acetamide; methanol; dichloromethane; water; ethyl acetate	57%

6-hydroxy-1,2,3,4-tetrahydroisoquinoline (14446-24-3) + (2RS,4SR)-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-ylmethyl methanesulfonate (345649-43-6) → Cis (+/-)6-[[2-(2,4dichlorophenyl)-2-(1H-imidazol-1-yl-methyl)-1,3-dioxolan-4-yl]-methoxy]-1,2,3,4-tetrahydro-isoquinoline

Conditions	Yield
In methanol; dichloromethane; water; dimethyl sulfoxide	53%

2-Aminobenzyl alcohol (5344-90-1) + 6-hydroxy-1,2,3,4-tetrahydroisoquinoline (14446-24-3) → 3-hydroxy-5,6-dihydro-8H-isoquinolino[1,2-b]quinazolin-8-one

Conditions	Yield
With oxygen; 4-nitro-benzoic acid In para-xylene at 120℃; for 16h; chemoselective reaction;	51%

6-hydroxy-1,2,3,4-tetrahydroisoquinoline (14446-24-3) + 3-(3-Bromopropyl)-5-fluoro-1H-indole (191013-68-0) → 2-[3-(5-fluoro-1H-indol-3-yl)-propyl]-6-hydroxy-1,2,3,4-tetrahydro-isoquinoline (1045805-48-8)

Conditions	Yield
With triethylamine In dimethyl sulfoxide at 100℃; for 24h;	48%

6-hydroxy-1,2,3,4-tetrahydroisoquinoline (14446-24-3) + N,N-diethylcarbamyl chloride (88-10-8) → C14H20N2O2

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 12h;	48%

Cyclopentyl bromide (137-43-9) + 6-hydroxy-1,2,3,4-tetrahydroisoquinoline (14446-24-3) → 6-(cyclopentyloxy)-3,4-dihydroisoquinoline-2(1H)-carboxylic acid tert-butyl ester

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 100h;	1%

6-hydroxy-1,2,3,4-tetrahydroisoquinoline (14446-24-3) + trifluoroacetic acid-methyl ester (431-47-0) → 2-(trifluoroacetyl)-1,2,3,4-tetrahydro-6-isoquinolinol (216064-45-8)

Conditions	Yield
In N,N-dimethyl-formamide

6-hydroxy-1,2,3,4-tetrahydroisoquinoline (14446-24-3) + 2-Chloromethylbenzoyl chloride (42908-86-1) + (E)-4-phenylbut-3-en-1-amine (7515-38-0) → 2-(6-hydroxy-3,4-dihydro-1H-isoquinolin-2-ylmethyl)-N-(4-phenyl-but-3-enyl)-benzamide

Conditions	Yield
Multistep reaction;

6-hydroxy-1,2,3,4-tetrahydroisoquinoline (14446-24-3) → 6‐methoxy‐N‐methyl‐1,2,3,4‐tetrahydroisoquinoline (54893-54-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: dimethylformamide 2: p-TsOH*H2O / CH2Cl2 3: aq NaOH / dioxane View Scheme

6-hydroxy-1,2,3,4-tetrahydroisoquinoline (14446-24-3) → 6-ethoxy-2-methyl-1,2,3,4-tetrahydro-isoquinoline (59529-93-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: dimethylformamide 2: p-TsOH*H2O / CH2Cl2 3: aq NaOH / dioxane View Scheme

6-hydroxy-1,2,3,4-tetrahydroisoquinoline (14446-24-3) → 6-Isobutoxy-2-methyl-1,2,3,4-tetrahydro-isoquinoline

Conditions	Yield
Multi-step reaction with 4 steps 1: dimethylformamide 2: p-TsOH*H2O / CH2Cl2 3: aq NaOH / dioxane View Scheme

6-hydroxy-1,2,3,4-tetrahydroisoquinoline (14446-24-3) → 6-[((E)-But-2-enyl)oxy]-2-methyl-1,2,3,4-tetrahydro-isoquinoline

Conditions	Yield
Multi-step reaction with 4 steps 1: dimethylformamide 2: p-TsOH*H2O / CH2Cl2 3: aq NaOH / dioxane View Scheme

6-hydroxy-1,2,3,4-tetrahydroisoquinoline (14446-24-3) → 6-(tetrahydropyran-2-yloxy)-1,2,3,4-tetrahydroisoquinoline (200396-68-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: dimethylformamide 2: p-TsOH*H2O / CH2Cl2 3: aq NaOH / dioxane View Scheme

6-hydroxy-1,2,3,4-tetrahydroisoquinoline (14446-24-3) → 2-methyl-6-(4-phenylbutoxy)-1,2,3,4-tetrahydroisoquinoline

Conditions	Yield
Multi-step reaction with 4 steps 1: dimethylformamide 2: p-TsOH*H2O / CH2Cl2 3: aq NaOH / dioxane View Scheme

6-hydroxy-1,2,3,4-tetrahydroisoquinoline (14446-24-3) → 6-(tetrahydropyran-2-yloxy)-2-trifluoroacetyl-1,2,3,4-tetrahydroisoquinoline (216064-47-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: dimethylformamide 2: p-TsOH*H2O / CH2Cl2 View Scheme

6-hydroxy-1,2,3,4-tetrahydroisoquinoline (14446-24-3) + 3,5-bis(trifluoromethyl)benzyl bromide (32247-96-4) → 2-(3,5-bis-trifluoromethyl-benzyl)-1,2,3,4-tetrahydro-isoquinolin-6-ol

Conditions	Yield
With potassium carbonate In acetonitrile at 20℃; for 16h;

6-hydroxy-1,2,3,4-tetrahydroisoquinoline (14446-24-3) + (E)-1-(4-chlorophenyl)-3-chloropropene (103979-29-9) → (E)-2-[3-(4-chlorophenyl)-2-propenyl]-1,2,3,4-tetrahydro-6-isoquinolinol (263395-26-2)

Conditions	Yield
With potassium carbonate In dichloromethane; water; N,N-dimethyl-formamide

thiophene-2-carbaldehyde (98-03-3) + 6-hydroxy-1,2,3,4-tetrahydroisoquinoline (14446-24-3) + toluenesulfonic acid monohydrate → 6-Hydroxy-2-(thien-2-ylmethyl)-1,2,3,4-tetrahydroisoquinoline

Conditions	Yield
With sodium cyanoborohydride In ethanol; dichloromethane; ethyl acetate

6-hydroxy-1,2,3,4-tetrahydroisoquinoline (14446-24-3) + diethylamine (109-89-7) + acetyl chloride (75-36-5) → 1-(6-hydroxy-3,4-dihydroisoquinolin-2(1H)-yl)ethan-1-one (59839-29-1)

Conditions	Yield
With acetic anhydride; triethylamine In methanol; ethanol; ethyl acetate

6-hydroxy-1,2,3,4-tetrahydroisoquinoline (14446-24-3) + 4-chloro-benzoyl chloride (122-01-0) → 6-Hydroxy-2-(4-chlorobenzoyl)-1,2,3,4-tetrahydroisoquinoline

Conditions	Yield
With hydrogenchloride; triethylamine In dichloromethane

Upstream product

• 42923-77-3 6-methoxy-1,2,3,4-tetrahydro-isoquinoline 
• 50-00-0 formaldehyd 
• 3458-98-8 3-hydroxyphenylethylamine hydrochloride 
• 536-21-0 norfenefrine 
• 2039-67-0 2-(3-methoxyphenyl)-1-ethanamine 
• 63905-73-7 6-hydroxy-1,2,3,4-tetrahydroisoquinoline hydrochloride 
• 22245-98-3 6-hydroxy-3,4-dihydro-2H-isoquinolin-1-one 
• 588-05-6 m-tyramine 

Downstream Products

• 54893-54-8 6‐methoxy‐N‐methyl‐1,2,3,4‐tetrahydroisoquinoline 
• 263395-26-2 (E)-2-[3-(4-chlorophenyl)-2-propenyl]-1,2,3,4-tetrahydro-6-isoquinolinol 
• 158984-83-9 N-tert-butoxycarbonyl-6-hydroxy-1,2,3,4-tetrahydroisoquinoline 
• 1281902-53-1 2-(phenylsulfonyl)-1,2,3,4-tetrahydro-6-isoquinolinol 
• 851784-78-6 C₁₅H₁₆Cl₂F₃NO₅S 
• 851784-80-0 2-(tert-butyl) 6-methyl 5,7-dichloro-3,4-dihydroisoquinoline-2,6(1Η)-dicarboxylate 
• 851784-82-2 2-(tert-butoxycarbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxylic acid 
• 851784-76-4 tert-butyl 5,7-dichloro-6-hydroxy-3,4-dihydroisoquinoline-2(1H)-carboxylate 
• 1194550-65-6 benzyl (S)-2-(5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-[3-(methylsulfonyl)phenyl]propanoate hydrochloride 
• 1194550-67-8 ((S)-benzyl 2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(3-methylsulfonyl)phenyl)propanoate 
• 1025967-78-5 (S)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoic acid 
• 1184745-98-9 (S)-isopropyl6-(1-(2-fluoro-4-(methylsulfonyl)phenyl)pyrrolidin-3-yloxy)-3,4-dihydroisoquinorine-2(1H)-carboxylate 
• 158984-84-0 6-trifluoromethanesulfonyloxy-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester 

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