65043-22-3

Usage

Uses

Used in Pharmaceutical Industry:
Indeloxazine hydrochloride is used as a therapeutic agent for the treatment of senile dementia, aiming to improve cognitive function and alleviate symptoms associated with the condition.
Used as an Antidepressant:
Indeloxazine hydrochloride is also utilized as an antidepressant, potentially providing relief from depressive symptoms and improving overall mood and well-being.

Originator

Yamanouchi (Japan)

Metabolic pathway

After oral administration of indeloxazine hydrochloride to rats, two conjugates, which are labile to a- glucosidase hydrolysis but refractory to b-glucosidase, are isolated from the urine and identified as a-D- glucopyranosides of trans-4-(2-morpholinylmethoxy)- 1,2-indandiol and trans-6-[[(1,2-dihydroxy-4- indanyl)oxy]-methyl]-3-morpholinone.

InChI:InChI=1/C14H17NO2.ClH/c1-3-11-4-2-6-14(13(11)5-1)17-10-12-9-15-7-8-16-12;/h1-4,6,12,15H,5,7-10H2;1H

Synthetic route

(+/-)-2-<(1-hydoxyindan-4-yloxy)methyl>-4-triphenylmethylmorpholine (64966-73-0) → 2-(7-indenyloxymethyl)-morpholine hydrochloride (65043-22-3)

Conditions	Yield
With hydrogenchloride In ethanol for 17h; Heating;	73.4%

sulfuric acid mono-(2-amino-ethyl ester) (926-39-6) + 1-(inden-7-yloxy)-2,3-epoxypropane (30190-85-3) → 2-(7-indenyloxymethyl)-morpholine hydrochloride (65043-22-3)

Conditions	Yield
With hydrogenchloride; sodium hydroxide In methanol 1.) 55 deg C, 16 h; 2.) iso-PrOH, acetone, 0-5 deg C, 15 min.;	73%

(+/-)-2-<(1-oxoindan-4-yloxy)methyl>-4-triphenylmethylmorpholine (60929-58-0) → 2-(7-indenyloxymethyl)-morpholine hydrochloride (65043-22-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 77.7 percent / LiAlH4 / tetrahydrofuran / 3 h / Ambient temperature 2: 73.4 percent / 0.5 N HCl / ethanol / 17 h / Heating View Scheme

R,S-2-hydroxymethyl-4-benzylmorpholine (40987-24-4) → 2-(7-indenyloxymethyl)-morpholine hydrochloride (65043-22-3)

Conditions

Yield

Multi-step reaction with 6 steps 1: 95 percent / H2 / 10percent Pd-C / methanol / Ambient temperature 2: 96.4 percent / Et3N / CH2Cl2 / 10 h / Ambient temperature 3: 70 percent / pyridine / CH2Cl2 / 15 h / Ambient temperature 4: 73.5 percent / dimethylformamide / 17 h / 100 - 105 °C 5: 77.7 percent / LiAlH4 / tetrahydrofuran / 3 h / Ambient temperature 6: 73.4 percent / 0.5 N HCl / ethanol / 17 h / Heating View Scheme

morpholin-2-ylmethanol (103003-01-6) → 2-(7-indenyloxymethyl)-morpholine hydrochloride (65043-22-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: 96.4 percent / Et3N / CH2Cl2 / 10 h / Ambient temperature 2: 70 percent / pyridine / CH2Cl2 / 15 h / Ambient temperature 3: 73.5 percent / dimethylformamide / 17 h / 100 - 105 °C 4: 77.7 percent / LiAlH4 / tetrahydrofuran / 3 h / Ambient temperature 5: 73.4 percent / 0.5 N HCl / ethanol / 17 h / Heating View Scheme

(+/)-2-hydroxymethyl-4-triphenylmethylmorpholine (131965-77-0) → 2-(7-indenyloxymethyl)-morpholine hydrochloride (65043-22-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: 70 percent / pyridine / CH2Cl2 / 15 h / Ambient temperature 2: 73.5 percent / dimethylformamide / 17 h / 100 - 105 °C 3: 77.7 percent / LiAlH4 / tetrahydrofuran / 3 h / Ambient temperature 4: 73.4 percent / 0.5 N HCl / ethanol / 17 h / Heating View Scheme

2-(p-toluenesulfonyloxymethyl)-4-triphenylmethylmorpholine (60929-57-9) → 2-(7-indenyloxymethyl)-morpholine hydrochloride (65043-22-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 73.5 percent / dimethylformamide / 17 h / 100 - 105 °C 2: 77.7 percent / LiAlH4 / tetrahydrofuran / 3 h / Ambient temperature 3: 73.4 percent / 0.5 N HCl / ethanol / 17 h / Heating View Scheme

4-morpholin-2-ylmethoxy-indan-1-ol (60929-60-4) → 2-(7-indenyloxymethyl)-morpholine hydrochloride (65043-22-3)

Conditions	Yield
With hydrogenchloride; sodium chloride In ethanol; chloroform; acetone

2-(7-indenyloxymethyl)-morpholine hydrochloride (65043-22-3) → (+)-indeloxazine hydrochloride, (+)-YM-08054 hydrochloride (65043-22-3, 76489-35-5, 104908-10-3, 104908-43-2)

Conditions	Yield
Yield given;

2-(7-indenyloxymethyl)-morpholine hydrochloride (65043-22-3) → (-)-indeloxazine hydrochloride; (-)-YM-08054 hydrochloride (65043-22-3, 76489-35-5, 104908-10-3, 104908-43-2)

Conditions	Yield
Yield given;

Upstream product

• 64966-73-0 (+/-)-2-<(1-hydoxyindan-4-yloxy)methyl>-4-triphenylmethylmorpholine 
• 60929-57-9 2-(p-toluenesulfonyloxymethyl)-4-triphenylmethylmorpholine 
• 103003-01-6 morpholin-2-ylmethanol 
• 60929-58-0 (+/-)-2-<(1-oxoindan-4-yloxy)methyl>-4-triphenylmethylmorpholine 
• 60929-60-4 4-morpholin-2-ylmethoxy-indan-1-ol 
• 926-39-6 sulfuric acid mono-(2-amino-ethyl ester) 
• 30190-85-3 1-(inden-7-yloxy)-2,3-epoxypropane 
• 40987-24-4 R,S-2-hydroxymethyl-4-benzylmorpholine 
• 131965-77-0 (+/)-2-hydroxymethyl-4-triphenylmethylmorpholine 

Downstream Products

• 65043-22-3 (+)-indeloxazine hydrochloride, (+)-YM-08054 hydrochloride 
• 65043-22-3 (-)-indeloxazine hydrochloride; (-)-YM-08054 hydrochloride 

Relevant academic research and scientific papers

2-(Indenyloxymethyl) morpholine derivatives

2-(Indenyloxymethyl) morpholine derivatives are disclosed. These derivatives are excellent in methamphetamine stereotyped increasing and antireserpine activities which are useful as antidepression agents.