73344-75-9

Basic information

• Product Name: C-(3,4-DIMETHOXY-BICYCLO[4.2.0]OCTA-1(6),2,4-TRIEN-7-YL)-METHYLAMINE
• Synonyms: C-(3,4-DIMETHOXY-BICYCLO[4.2.0]OCTA-1(6),2,4-TRIEN-7-YL)-METHYLAMINE;3,4-Dimethoxybicyclo[4.2.0]octa-1,3,5-triene-7-methanamine;4,5-Dimethoxy-1-(aminomethyl)benzocyclobutane;Bicyclo[4.2.0]octa-1,3,5-triene-7-MethanaMine, 3,4-diMethoxy-;(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methanamine;Ivabradine Impurity 18;4,5-Dimethoxy-1-(aminomethyl)benzocyclobutane HCl;(4,5-DIMETHOXY-1,2-DIHYDROCYCLOBUTABENZEN-1-YL)METHANAMINE
• CAS NO: 73344-75-9
• Molecular Formula: C₁₁H₁₅NO₂
• Molecular Weight: 193.24
• Mol File: 73344-75-9.mol
• Article Data: 2

Chemical Properties

• Boiling Point: 309℃
• Flash Point: 153℃
• Appearance: /
• Density: 1.113
• Storage Temp.: 2-8°C
• Solubility: DMSO (Slightly), Methanol (Slightly)
• CAS DataBase Reference: C-(3,4-DIMETHOXY-BICYCLO[4.2.0]OCTA-1(6),2,4-TRIEN-7-YL)-METHYLAMINE(CAS DataBase Reference)
• NIST Chemistry Reference: C-(3,4-DIMETHOXY-BICYCLO[4.2.0]OCTA-1(6),2,4-TRIEN-7-YL)-METHYLAMINE(73344-75-9)
• EPA Substance Registry System: C-(3,4-DIMETHOXY-BICYCLO[4.2.0]OCTA-1(6),2,4-TRIEN-7-YL)-METHYLAMINE(73344-75-9)

Safety Data

• Hazardous Substances Data: 73344-75-9(Hazardous Substances Data)

Usage

Uses

4,5-Dimethoxy-1-(aminomethyl)benzocyclobutane is used in the synthesis of ent-Ivabradine Hydrochloride (I940505), which is a selective bradycardic agent with direct effect on the pacemaker If current of the sinoatrial node. Also an antianginal.

Synthetic route

3,4-dimethoxy-bicyclo[4.2.0]octa-1,3,5-triene-7-carbonitrile (35202-54-1) → (±)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (73344-75-9)

Conditions	Yield
With ammonia; hydrogen; nickel In methanol at 60℃; under 22502.3 Torr; Industry scale;	100%
With ammonia; hydrogen In methanol at 20℃; under 2327.23 Torr; for 12h; Solvent; Reagent/catalyst;	98%

formic acid (64-18-6) + (±)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (73344-75-9) → C12H15NO3

Conditions	Yield
Stage #1: formic acid With 1,1'-carbonyldiimidazole In tetrahydrofuran at 20℃; for 0.25h; Stage #2: (±)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine In tetrahydrofuran at 20℃; for 12h; Reagent/catalyst; Temperature; Solvent;	90%

N-acetyl-(S)-glutamic acid (1188-37-0) + (±)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (73344-75-9) → (1S)-4,5-dimethoxy-1-(aminomethyl)-benzocyclobutane N-acetyl-L-glutamate (869856-08-6)

Conditions	Yield
In ethanol; water at 20℃; Heating / reflux; Industry scale;	40%

(±)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (73344-75-9) + (S)-ibuprofen (51146-56-6) → C11H15NO2*2C13H18O2

Conditions	Yield
In acetonitrile at 20℃; for 24h; Solvent;	40%

(±)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (73344-75-9) + (S)-ibuprofen (51146-56-6) → C11H15NO2*2C13H18O2 + C11H15NO2*2C13H18O2

Conditions	Yield
In acetonitrile at 20 - 42℃; for 20h; Temperature; Time; Solvent;	A 38% B n/a

diallylcarbonate (15022-08-9) + (±)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (73344-75-9) → (1S)-4,5-dimethoxy-1-(ammoniummethyl)benzocyclobutane (869856-07-5) + (R)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (1422007-49-5) + allyl {[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}carbamate + allyl {[(7R)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}carbamate

Conditions	Yield
With Pseudomonas cepacia lipase II In 2-methyltetrahydrofuran at 30℃; for 42h;	A n/a B n/a C 35% D n/a
With lipase from Pseudomonas fluorescens In tert-butyl methyl ether at 30℃; for 24h; Catalytic behavior; Reagent/catalyst; Resolution of racemate; Inert atmosphere; Enzymatic reaction; enantioselective reaction;	A n/a B n/a C n/a D n/a

DBC (3459-92-5) + (±)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (73344-75-9) → (1S)-4,5-dimethoxy-1-(ammoniummethyl)benzocyclobutane (869856-07-5) + (R)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (1422007-49-5) + benzyl {[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}carbamate

Conditions	Yield
With Pseudomonas cepacia lipase II In 2-methyltetrahydrofuran at 30℃; for 24h;	A n/a B n/a C 30%

but-3-enoyl chloride (1470-91-3) + (±)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (73344-75-9) → N-<(4,5-dimethoxybenzocyclobutenyl)methyl>-3-butenamide (73348-43-3)

Conditions	Yield
With pyridine In dichloromethane	29%

(±)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (73344-75-9) → cis-8,9-dimethoxy-1,2,3,4,4a,5,6,10b-octahydrobenzisoquinoline (73344-71-5, 73344-77-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: 29 percent / pyridine / CH2Cl2 2: 57 percent / various solvent(s) / 18 h / Heating 3: LiAlH4, AlCl3 / diethyl ether / 2.25 h / Ambient temperature View Scheme

(±)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (73344-75-9) → cis-N-n-propyl-8,9-dimethoxy-1,2,3,4,4a,5,6,10b-octahydrobenzisoquinoline

Conditions	Yield
Multi-step reaction with 4 steps 1: 29 percent / pyridine / CH2Cl2 2: 57 percent / various solvent(s) / 18 h / Heating 3: LiAlH4, AlCl3 / diethyl ether / 2.25 h / Ambient temperature 4: NaBH4 / benzene View Scheme

(±)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (73344-75-9) → cis-8,9-dimethoxy-1,2,3,4,4a,5,6,10b-octahydrobenzisoquinolin-3-one (73344-76-0, 73344-85-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 29 percent / pyridine / CH2Cl2 2: 57 percent / various solvent(s) / 18 h / Heating View Scheme

diallylcarbonate (15022-08-9) + (±)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (73344-75-9) → (R)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (1422007-49-5) + allyl {[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}carbamate + allyl {[(7R)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}carbamate

Conditions	Yield
With lipase from Pseudomonas Cepacia In tert-butyl methyl ether at 30℃; for 24h; Catalytic behavior; Reagent/catalyst; Resolution of racemate; Inert atmosphere; Enzymatic reaction; enantioselective reaction;	A n/a B n/a C n/a
With Pseudomonas cepacia lipase II In tert-butyl methyl ether at 30℃; for 24h;	A n/a B n/a C n/a

DBC (3459-92-5) + (±)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (73344-75-9) → (R)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (1422007-49-5) + benzyl {[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}carbamate + benzyl {[(7R)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}carbamate

Conditions	Yield
With lipase from Pseudomonas Cepacia In tert-butyl methyl ether at 30℃; for 24h; Resolution of racemate; Inert atmosphere; Enzymatic reaction; enantioselective reaction;	A n/a B n/a C n/a
With Pseudomonas cepacia lipase II In tert-butyl methyl ether at 30℃; for 24h;	A n/a B n/a C n/a

DBC (3459-92-5) + (±)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (73344-75-9) → (1S)-4,5-dimethoxy-1-(ammoniummethyl)benzocyclobutane (869856-07-5) + (R)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (1422007-49-5) + benzyl {[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}carbamate + benzyl {[(7R)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}carbamate

Conditions	Yield
With lipase from Pseudomonas fluorescens In tert-butyl methyl ether at 30℃; for 24h; Catalytic behavior; Reagent/catalyst; Resolution of racemate; Inert atmosphere; Enzymatic reaction; enantioselective reaction;	A n/a B n/a C n/a D n/a
With Pseudomonas cepacia lipase II In tert-butyl methyl ether at 30℃; for 24h;	A n/a B n/a C n/a D n/a

(±)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (73344-75-9) + Diethyl carbonate (105-58-8) → ethyl {[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}carbamate (869856-10-0) + ethyl {[(7R)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}carbamate

Conditions	Yield
With lipase from Pseudomonas Cepacia In 2-methyltetrahydrofuran at 30℃; for 48h; Inert atmosphere; Enzymatic reaction; Overall yield = 44 %; enantioselective reaction;	A n/a B n/a

(±)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (73344-75-9) + Diethyl carbonate (105-58-8) → ethyl {[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}carbamate (869856-10-0) + (R)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (1422007-49-5) + ethyl {[(7R)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}carbamate

Conditions	Yield
With lipase from Pseudomonas Cepacia In 2-methyltetrahydrofuran at 30℃; for 96h; Concentration; Resolution of racemate; Inert atmosphere; Enzymatic reaction; enantioselective reaction;	A n/a B n/a C n/a
With Pseudomonas cepacia lipase II In 2-methyltetrahydrofuran at 30℃; for 96h; Enzymatic reaction;	A n/a B n/a C n/a
With Pseudomonas cepacia lipase II In 2-methyltetrahydrofuran at 30℃; for 24h; Enzymatic reaction;	A n/a B n/a C n/a

(±)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (73344-75-9) + Diethyl carbonate (105-58-8) → (1S)-4,5-dimethoxy-1-(ammoniummethyl)benzocyclobutane (869856-07-5) + ethyl {[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}carbamate (869856-10-0) + (R)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (1422007-49-5)

Conditions	Yield
With lipase from Pseudomonas Cepacia In 2-methyltetrahydrofuran at 30℃; for 24h; Solvent; Concentration; Resolution of racemate; Inert atmosphere; Enzymatic reaction; enantioselective reaction;	A n/a B n/a C n/a
With Pseudomonas cepacia lipase II In 2-methyltetrahydrofuran at 30℃; for 24h; Enzymatic reaction;	A n/a B n/a C n/a

(±)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (73344-75-9) + ethyl acetate (141-78-6) → (R)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (1422007-49-5) + (S)-N-((3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methyl)acetamide + (R)-N-((3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methyl)acetamide

Conditions	Yield
With lipase PS IM at 30℃; for 4h; Catalytic behavior; Reagent/catalyst; Resolution of racemate; Inert atmosphere; Enzymatic reaction; enantioselective reaction;	A n/a B n/a C n/a

(±)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (73344-75-9) + ethyl acetate (141-78-6) → (1S)-4,5-dimethoxy-1-(ammoniummethyl)benzocyclobutane (869856-07-5) + (R)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (1422007-49-5) + (S)-N-((3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methyl)acetamide + (R)-N-((3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methyl)acetamide

Conditions	Yield
With lipase from Pseudomonas fluorescens at 30℃; for 4h; Catalytic behavior; Reagent/catalyst; Resolution of racemate; Inert atmosphere; Enzymatic reaction; enantioselective reaction;	A n/a B n/a C n/a D n/a

(±)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (73344-75-9) + 1-phenylethyl acetate (93-92-5, 50373-55-2) → (1S)-4,5-dimethoxy-1-(ammoniummethyl)benzocyclobutane (869856-07-5) + (R)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (1422007-49-5) + (S)-N-((3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methyl)acetamide + (R)-N-((3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methyl)acetamide

Conditions	Yield
With lipase from Pseudomonas Cepacia In tert-butyl methyl ether at 30℃; for 96h; Catalytic behavior; Reagent/catalyst; Resolution of racemate; Inert atmosphere; Enzymatic reaction; enantioselective reaction;	A n/a B n/a C n/a D n/a

(±)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (73344-75-9) + chloroacetic acid ethyl ester (105-39-5) → C13H16ClNO3 + C13H16ClNO3

Conditions	Yield
With lipase from Pseudomonas Cepacia In tert-butyl methyl ether at 30℃; for 96h; Catalytic behavior; Reagent/catalyst; Inert atmosphere; Enzymatic reaction; enantioselective reaction;	A n/a B n/a

(±)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (73344-75-9) + chloroacetic acid ethyl ester (105-39-5) → C13H16ClNO3

Conditions	Yield
With lipase from Pseudomonas fluorescens In tert-butyl methyl ether at 30℃; for 96h; Inert atmosphere; Enzymatic reaction;

methyl methoxyacetate (6290-49-9) + (±)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (73344-75-9) → (1S)-4,5-dimethoxy-1-(ammoniummethyl)benzocyclobutane (869856-07-5) + (R)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (1422007-49-5) + (S)-N-((3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methyl)-2-methoxyacetamide + (R)-N-((3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methyl)-2-methoxyacetamide

Conditions	Yield
With lipase from Pseudomonas Cepacia In tert-butyl methyl ether at 30℃; for 96h; Catalytic behavior; Reagent/catalyst; Resolution of racemate; Inert atmosphere; Enzymatic reaction; enantioselective reaction;	A n/a B n/a C n/a D n/a

(±)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (73344-75-9) → [{(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl}methyl](methyl)amine (866783-12-2)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 0.25 h / 20 °C 1.2: 12 h / 20 °C 2.1: boron trifluoride-tetrahydrofuran complex / tetrahydrofuran / 8 h / 0 - 20 °C 3.1: ethanol / 1 h / Reflux 4.1: sodium hydroxide / ethanol; water; dichloromethane / 1 h / 20 °C / pH 10 - 11 View Scheme
Multi-step reaction with 4 steps 1.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 0.25 h / 20 °C 1.2: 12 h / 20 °C 2.1: boron trifluoride-tetrahydrofuran complex / tetrahydrofuran / 8 h / 0 - 20 °C 3.1: ethanol; Isopropyl acetate / 1 h / Reflux 4.1: sodium hydroxide / water; dichloromethane / 1 h / 20 °C / pH 10 - 11 View Scheme

(±)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (73344-75-9) → ivabradine hydrochloride (148849-67-6)

Conditions	Yield
Multi-step reaction with 7 steps 1.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 0.25 h / 20 °C 1.2: 12 h / 20 °C 2.1: boron trifluoride-tetrahydrofuran complex / tetrahydrofuran / 8 h / 0 - 20 °C 3.1: ethanol / 1 h / Reflux 4.1: sodium hydroxide / ethanol; water; dichloromethane / 1 h / 20 °C / pH 10 - 11 5.1: acetic acid / ethanol / 0.5 h / 20 °C 5.2: 1 h / 15 - 20 °C 6.1: triethylamine / acetonitrile / 12 h / 20 °C 7.1: hydrogenchloride; pyrographite / acetonitrile / 0.17 h / 70 °C / pH 2 - 3 View Scheme
Multi-step reaction with 7 steps 1.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 0.25 h / 20 °C 1.2: 12 h / 20 °C 2.1: boron trifluoride-tetrahydrofuran complex / tetrahydrofuran / 8 h / 0 - 20 °C 3.1: ethanol; Isopropyl acetate / 1 h / Reflux 4.1: sodium hydroxide / water; dichloromethane / 1 h / 20 °C / pH 10 - 11 5.1: acetic acid / ethanol / 0.5 h / 20 °C 5.2: 1 h / 15 - 20 °C 6.1: triethylamine / acetonitrile / 12 h / 20 °C 7.1: hydrogenchloride; pyrographite / acetonitrile / 0.17 h / 70 °C / pH 2 - 3 View Scheme

(±)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (73344-75-9) → ivabradine (155974-00-8)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 0.25 h / 20 °C 1.2: 12 h / 20 °C 2.1: boron trifluoride-tetrahydrofuran complex / tetrahydrofuran / 8 h / 0 - 20 °C 3.1: ethanol / 1 h / Reflux 4.1: sodium hydroxide / ethanol; water; dichloromethane / 1 h / 20 °C / pH 10 - 11 5.1: acetic acid / ethanol / 0.5 h / 20 °C 5.2: 1 h / 15 - 20 °C 6.1: triethylamine / acetonitrile / 12 h / 20 °C View Scheme
Multi-step reaction with 6 steps 1.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 0.25 h / 20 °C 1.2: 12 h / 20 °C 2.1: boron trifluoride-tetrahydrofuran complex / tetrahydrofuran / 8 h / 0 - 20 °C 3.1: ethanol; Isopropyl acetate / 1 h / Reflux 4.1: sodium hydroxide / water; dichloromethane / 1 h / 20 °C / pH 10 - 11 5.1: acetic acid / ethanol / 0.5 h / 20 °C 5.2: 1 h / 15 - 20 °C 6.1: triethylamine / acetonitrile / 12 h / 20 °C View Scheme

(±)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (73344-75-9) → (1S)-4,5-dimethoxy-1-[(methylamino)methyl]benzocyclobutane N-acetyl-L-glutamic acid

Conditions	Yield
Multi-step reaction with 3 steps 1.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 0.25 h / 20 °C 1.2: 12 h / 20 °C 2.1: boron trifluoride-tetrahydrofuran complex / tetrahydrofuran / 8 h / 0 - 20 °C 3.1: ethanol / 1 h / Reflux View Scheme

(±)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (73344-75-9) → (1S)-4,5-dimethoxy-1-[(methylamino)methyl]benzocyclobutane dextro mandelate

Conditions	Yield
Multi-step reaction with 3 steps 1.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 0.25 h / 20 °C 1.2: 12 h / 20 °C 2.1: boron trifluoride-tetrahydrofuran complex / tetrahydrofuran / 8 h / 0 - 20 °C 3.1: ethanol; Isopropyl acetate / 1 h / Reflux View Scheme

(±)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (73344-75-9) → ({3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl}methyl)(methyl)amine (148870-56-8)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 0.25 h / 20 °C 1.2: 12 h / 20 °C 2.1: boron trifluoride-tetrahydrofuran complex / tetrahydrofuran / 8 h / 0 - 20 °C View Scheme

(±)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine (73344-75-9) → 1-[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]-N-methylmethanamine hydrochloride (866783-13-3)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 0.25 h / 20 °C 1.2: 12 h / 20 °C 2.1: boron trifluoride-tetrahydrofuran complex / tetrahydrofuran / 8 h / 0 - 20 °C 3.1: ethanol / 1 h / Reflux 4.1: sodium hydroxide / ethanol; water; dichloromethane / 1 h / 20 °C / pH 10 - 11 5.1: acetic acid / ethanol / 0.5 h / 20 °C 5.2: 1 h / 15 - 20 °C View Scheme
Multi-step reaction with 5 steps 1.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 0.25 h / 20 °C 1.2: 12 h / 20 °C 2.1: boron trifluoride-tetrahydrofuran complex / tetrahydrofuran / 8 h / 0 - 20 °C 3.1: ethanol; Isopropyl acetate / 1 h / Reflux 4.1: sodium hydroxide / water; dichloromethane / 1 h / 20 °C / pH 10 - 11 5.1: acetic acid / ethanol / 0.5 h / 20 °C 5.2: 1 h / 15 - 20 °C View Scheme

Upstream product

• 35202-54-1 3,4-dimethoxy-bicyclo[4.2.0]octa-1,3,5-triene-7-carbonitrile 

Downstream Products

• 866783-13-3 1-[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]-N-methylmethanamine hydrochloride 
• 148870-56-8 ({3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl}methyl)(methyl)amine 
• 155974-00-8 ivabradine 
• 148849-67-6 ivabradine hydrochloride 
• 866783-12-2 [{(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl}methyl](methyl)amine 
• 869856-07-5 (1S)-4,5-dimethoxy-1-(ammoniummethyl)benzocyclobutane 
• 1422007-49-5 (R)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methylamine 

Relevant articles and documents

(1 S) - 4, 5 - dimethoxy - 1 - [(methylamino) methyl] benzocyclobutane preparation of hydrochloride salts of method

The invention provides a preparation method of (1S)-4,5-dimethoxy-1-[(methylamino)methyl]benzocyclobutane hydrochloride, which specially comprises the following step: carrying out reduction and salting-out on 4,5-dimethoxybenzocyclobutyl-1-methyl formamide in an inert solvent to finally obtain the (1S)-4,5-dimethoxy-1-[(methylamino)methyl]benzocyclobutane hydrochloride (I). The reaction is simple to operate, has the advantages of mild reaction conditions, clean and accessible raw/auxiliary materials, low overall cost, high chemical and enantiomer purity and the like, and therefore, is suitable for industrial production.