754159-68-7

Usage

Uses

Used in Pharmaceutical Industry:
IB-MECA is used as a therapeutic agent for the treatment of various inflammatory and autoimmune diseases, such as rheumatoid arthritis, psoriasis, and inflammatory bowel disease. Its agonistic action on the adenosine A3 receptor helps in reducing inflammation and alleviating the symptoms associated with these conditions.
Used in Oncology:
IB-MECA is used as an anticancer agent, where it exhibits properties such as inhibiting cell proliferation, reducing inflammation, and promoting apoptosis in cancer cells. Its ability to modulate various signaling pathways involved in cancer progression makes it a promising candidate for cancer therapy.
Used in Drug Development Research:
In the field of drug development, IB-MECA serves as a valuable research tool for studying the role of adenosine A3 receptors in various physiological and pathological processes. Understanding its mechanism of action can aid in the design of novel therapeutic agents targeting this receptor for the treatment of different diseases.

Synthetic route

(E)-3-phenylacrylic acid (140-10-3) → 4-(benzyloxy)-3-[(1R)-3-(dipropan-2-ylamino)-1-phenylpropyl]benzoic acid (754159-68-7)

Conditions

Yield

Multi-step reaction with 8 steps 1.1: sulfuric acid / 120 - 125 °C 2.1: potassium carbonate; sodium iodide / acetone / Reflux 3.1: sodium tetrahydroborate / 1,2-dimethoxyethane / 0.17 h 3.2: 3 h / 10 °C 4.1: triethylamine / dichloromethane / 12 h / 25 - 30 °C 5.1: acetonitrile / 30 h / 95 - 100 °C / autoclave; Sealed tube 6.1: isopropyl alcohol / 15 h / 25 - 86 °C 7.1: sodium hydroxide / water 8.1: ethyl bromide; iodine; magnesium / tetrahydrofuran / 1 h / 55 °C / Reflux 8.2: 1 h / -65 - -60 °C View Scheme

R-(-)-[3-(2-benzyloxy-5-bromophenyl)-3-phenylpropyl]diisopropylamine (950773-38-3) + carbon dioxide (124-38-9) → 4-(benzyloxy)-3-[(1R)-3-(dipropan-2-ylamino)-1-phenylpropyl]benzoic acid (754159-68-7)

Conditions	Yield
Stage #1: R-(-)-[3-(2-benzyloxy-5-bromophenyl)-3-phenylpropyl]diisopropylamine With ethyl bromide; iodine; magnesium In tetrahydrofuran at 55℃; for 1h; Reflux; Stage #2: carbon dioxide In tetrahydrofuran at -65 - -60℃; for 1h;
Stage #1: R-(-)-[3-(2-benzyloxy-5-bromophenyl)-3-phenylpropyl]diisopropylamine With ethyl bromide; iodine; magnesium In tetrahydrofuran at 60 - 65℃; for 2h; Inert atmosphere; Stage #2: carbon dioxide In tetrahydrofuran at -70 - -50℃; for 1h;

(+/-)-3-(2-benzyloxy-5-bromophenyl)-3-phenylpropane-1-ol → 4-(benzyloxy)-3-[(1R)-3-(dipropan-2-ylamino)-1-phenylpropyl]benzoic acid (754159-68-7)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: triethylamine / dichloromethane / 12 h / 25 - 30 °C 2.1: acetonitrile / 30 h / 95 - 100 °C / autoclave; Sealed tube 3.1: isopropyl alcohol / 15 h / 25 - 86 °C 4.1: sodium hydroxide / water 5.1: ethyl bromide; iodine; magnesium / tetrahydrofuran / 1 h / 55 °C / Reflux 5.2: 1 h / -65 - -60 °C View Scheme
Multi-step reaction with 6 steps 1.1: dmap; triethylamine / dichloromethane / 20 °C 2.1: potassium iodide / acetonitrile / 15 h / Reflux 3.1: ethyl bromide; iodine; magnesium / tetrahydrofuran / Reflux 3.2: 1 h / -60 - -25 °C 3.3: 1 h / 0 - 20 °C 4.1: ammonia / ethyl acetate; water / pH 8 - 9 5.1: methanol / 50 - 65 °C 6.1: ammonia / water / pH 8 - 9 View Scheme
Multi-step reaction with 4 steps 1.1: dmap; triethylamine / dichloromethane / 2 h / 0 - 5 °C 2.1: acetonitrile / 32 h / 95 - 100 °C / autoclave; Inert atmosphere 3.1: ethyl bromide; iodine; magnesium / tetrahydrofuran / 4 h / 50 - 55 °C / Inert atmosphere 3.2: 1.5 h / -70 - -60 °C / Inert atmosphere 3.3: -10 - 25 °C 4.1: D-tartaric acid / isopropyl alcohol / 16 h / 30 - 35 °C 4.2: 10 - 15 °C View Scheme

(+/-)-N,N-diisopropyl-3-(2-benzyloxy-5-bromophenyl)-3-phenylpropylamine → 4-(benzyloxy)-3-[(1R)-3-(dipropan-2-ylamino)-1-phenylpropyl]benzoic acid (754159-68-7)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: isopropyl alcohol / 15 h / 25 - 86 °C 2.1: sodium hydroxide / water 3.1: ethyl bromide; iodine; magnesium / tetrahydrofuran / 1 h / 55 °C / Reflux 3.2: 1 h / -65 - -60 °C View Scheme
Multi-step reaction with 4 steps 1.1: ethyl bromide; iodine; magnesium / tetrahydrofuran / Reflux 1.2: 1 h / -60 - -25 °C 1.3: 1 h / 0 - 20 °C 2.1: ammonia / ethyl acetate; water / pH 8 - 9 3.1: methanol / 50 - 65 °C 4.1: ammonia / water / pH 8 - 9 View Scheme
Multi-step reaction with 2 steps 1.1: ethyl bromide; iodine; magnesium / tetrahydrofuran / 4 h / 50 - 55 °C / Inert atmosphere 1.2: 1.5 h / -70 - -60 °C / Inert atmosphere 1.3: -10 - 25 °C 2.1: D-tartaric acid / isopropyl alcohol / 16 h / 30 - 35 °C 2.2: 10 - 15 °C View Scheme

4-bromo-phenol (106-41-2) → 4-(benzyloxy)-3-[(1R)-3-(dipropan-2-ylamino)-1-phenylpropyl]benzoic acid (754159-68-7)

Conditions	Yield
Multi-step reaction with 8 steps 1.1: sulfuric acid / 120 - 125 °C 2.1: potassium carbonate; sodium iodide / acetone / Reflux 3.1: sodium tetrahydroborate / 1,2-dimethoxyethane / 0.17 h 3.2: 3 h / 10 °C 4.1: triethylamine / dichloromethane / 12 h / 25 - 30 °C 5.1: acetonitrile / 30 h / 95 - 100 °C / autoclave; Sealed tube 6.1: isopropyl alcohol / 15 h / 25 - 86 °C 7.1: sodium hydroxide / water 8.1: ethyl bromide; iodine; magnesium / tetrahydrofuran / 1 h / 55 °C / Reflux 8.2: 1 h / -65 - -60 °C View Scheme
Multi-step reaction with 7 steps 1.1: sulfuric acid / 12 h / 120 - 125 °C 2.1: potassium carbonate; sodium iodide / acetone / 25 - 30 °C 2.2: 5.5 h / 15 °C / Reflux 3.1: sodium bis(2-methoxyethoxy)aluminium dihydride / toluene / 4 h / 5 - 10 °C / Inert atmosphere 4.1: dmap; triethylamine / dichloromethane / 2 h / 0 - 5 °C 5.1: acetonitrile / 32 h / 95 - 100 °C / autoclave; Inert atmosphere 6.1: ethyl bromide; iodine; magnesium / tetrahydrofuran / 4 h / 50 - 55 °C / Inert atmosphere 6.2: 1.5 h / -70 - -60 °C / Inert atmosphere 6.3: -10 - 25 °C 7.1: D-tartaric acid / isopropyl alcohol / 16 h / 30 - 35 °C 7.2: 10 - 15 °C View Scheme

6-bromo-4-phenyl-3,4-dihydro-2H-chromen-2-one (156755-23-6) → 4-(benzyloxy)-3-[(1R)-3-(dipropan-2-ylamino)-1-phenylpropyl]benzoic acid (754159-68-7)

Conditions	Yield
Multi-step reaction with 7 steps 1.1: potassium carbonate; sodium iodide / acetone / Reflux 2.1: sodium tetrahydroborate / 1,2-dimethoxyethane / 0.17 h 2.2: 3 h / 10 °C 3.1: triethylamine / dichloromethane / 12 h / 25 - 30 °C 4.1: acetonitrile / 30 h / 95 - 100 °C / autoclave; Sealed tube 5.1: isopropyl alcohol / 15 h / 25 - 86 °C 6.1: sodium hydroxide / water 7.1: ethyl bromide; iodine; magnesium / tetrahydrofuran / 1 h / 55 °C / Reflux 7.2: 1 h / -65 - -60 °C View Scheme
Multi-step reaction with 6 steps 1.1: potassium carbonate; sodium iodide / acetone / 25 - 30 °C 1.2: 5.5 h / 15 °C / Reflux 2.1: sodium bis(2-methoxyethoxy)aluminium dihydride / toluene / 4 h / 5 - 10 °C / Inert atmosphere 3.1: dmap; triethylamine / dichloromethane / 2 h / 0 - 5 °C 4.1: acetonitrile / 32 h / 95 - 100 °C / autoclave; Inert atmosphere 5.1: ethyl bromide; iodine; magnesium / tetrahydrofuran / 4 h / 50 - 55 °C / Inert atmosphere 5.2: 1.5 h / -70 - -60 °C / Inert atmosphere 5.3: -10 - 25 °C 6.1: D-tartaric acid / isopropyl alcohol / 16 h / 30 - 35 °C 6.2: 10 - 15 °C View Scheme
Multi-step reaction with 8 steps 1.1: potassium carbonate / 60 - 65 °C 2.1: sodium hydroxide / water / 45 - 50 °C 3.1: ethanol / 5.83 h / 0 - 75 °C 4.1: hydrogenchloride / water; toluene / 1 h / 20 - 25 °C 5.1: thionyl chloride; N,N-dimethyl-formamide / toluene / 50 - 55 °C 6.1: toluene / 1 h / 0 - 35 °C 7.1: tetrahydrofuran / 4.5 h / 60 - 65 °C 8.1: iodine; magnesium; ethyl bromide / tetrahydrofuran / 2 h / 60 - 65 °C / Inert atmosphere 8.2: 1 h / -70 - -50 °C View Scheme
Multi-step reaction with 8 steps 1.1: potassium carbonate / 60 - 65 °C 2.1: sodium hydroxide / water / 45 - 50 °C 3.1: ethanol / 5.83 h / 0 - 75 °C 4.1: hydrogenchloride / water; toluene / 1 h / 20 - 25 °C 5.1: thionyl chloride; N,N-dimethyl-formamide / toluene / 50 - 55 °C 6.1: toluene / 1 h / 0 - 35 °C 7.1: iodine; lithium aluminium tetrahydride / tetrahydrofuran / 2.25 h / 0 - 65 °C 8.1: iodine; magnesium; ethyl bromide / tetrahydrofuran / 2 h / 60 - 65 °C / Inert atmosphere 8.2: 1 h / -70 - -50 °C View Scheme

methyl 3-[2-(benzyloxy)-5-bromophenyl]-3-phenylpropanoate (156755-24-7) → 4-(benzyloxy)-3-[(1R)-3-(dipropan-2-ylamino)-1-phenylpropyl]benzoic acid (754159-68-7)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: sodium tetrahydroborate / 1,2-dimethoxyethane / 0.17 h 1.2: 3 h / 10 °C 2.1: triethylamine / dichloromethane / 12 h / 25 - 30 °C 3.1: acetonitrile / 30 h / 95 - 100 °C / autoclave; Sealed tube 4.1: isopropyl alcohol / 15 h / 25 - 86 °C 5.1: sodium hydroxide / water 6.1: ethyl bromide; iodine; magnesium / tetrahydrofuran / 1 h / 55 °C / Reflux 6.2: 1 h / -65 - -60 °C View Scheme
Multi-step reaction with 5 steps 1.1: sodium bis(2-methoxyethoxy)aluminium dihydride / toluene / 4 h / 5 - 10 °C / Inert atmosphere 2.1: dmap; triethylamine / dichloromethane / 2 h / 0 - 5 °C 3.1: acetonitrile / 32 h / 95 - 100 °C / autoclave; Inert atmosphere 4.1: ethyl bromide; iodine; magnesium / tetrahydrofuran / 4 h / 50 - 55 °C / Inert atmosphere 4.2: 1.5 h / -70 - -60 °C / Inert atmosphere 4.3: -10 - 25 °C 5.1: D-tartaric acid / isopropyl alcohol / 16 h / 30 - 35 °C 5.2: 10 - 15 °C View Scheme
Multi-step reaction with 7 steps 1.1: sodium hydroxide / water / 45 - 50 °C 2.1: ethanol / 5.83 h / 0 - 75 °C 3.1: hydrogenchloride / water; toluene / 1 h / 20 - 25 °C 4.1: thionyl chloride; N,N-dimethyl-formamide / toluene / 50 - 55 °C 5.1: toluene / 1 h / 0 - 35 °C 6.1: tetrahydrofuran / 4.5 h / 60 - 65 °C 7.1: iodine; magnesium; ethyl bromide / tetrahydrofuran / 2 h / 60 - 65 °C / Inert atmosphere 7.2: 1 h / -70 - -50 °C View Scheme
Multi-step reaction with 7 steps 1.1: sodium hydroxide / water / 45 - 50 °C 2.1: ethanol / 5.83 h / 0 - 75 °C 3.1: hydrogenchloride / water; toluene / 1 h / 20 - 25 °C 4.1: thionyl chloride; N,N-dimethyl-formamide / toluene / 50 - 55 °C 5.1: toluene / 1 h / 0 - 35 °C 6.1: iodine; lithium aluminium tetrahydride / tetrahydrofuran / 2.25 h / 0 - 65 °C 7.1: iodine; magnesium; ethyl bromide / tetrahydrofuran / 2 h / 60 - 65 °C / Inert atmosphere 7.2: 1 h / -70 - -50 °C View Scheme

(+/-)-toluene-4-sulphonic acid 3-(2-benzyloxy-5-bromophenyl)-3-phenylpropyl ester (250214-37-0) → 4-(benzyloxy)-3-[(1R)-3-(dipropan-2-ylamino)-1-phenylpropyl]benzoic acid (754159-68-7)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: acetonitrile / 30 h / 95 - 100 °C / autoclave; Sealed tube 2.1: isopropyl alcohol / 15 h / 25 - 86 °C 3.1: sodium hydroxide / water 4.1: ethyl bromide; iodine; magnesium / tetrahydrofuran / 1 h / 55 °C / Reflux 4.2: 1 h / -65 - -60 °C View Scheme
Multi-step reaction with 5 steps 1.1: potassium iodide / acetonitrile / 15 h / Reflux 2.1: ethyl bromide; iodine; magnesium / tetrahydrofuran / Reflux 2.2: 1 h / -60 - -25 °C 2.3: 1 h / 0 - 20 °C 3.1: ammonia / ethyl acetate; water / pH 8 - 9 4.1: methanol / 50 - 65 °C 5.1: ammonia / water / pH 8 - 9 View Scheme
Multi-step reaction with 3 steps 1.1: acetonitrile / 32 h / 95 - 100 °C / autoclave; Inert atmosphere 2.1: ethyl bromide; iodine; magnesium / tetrahydrofuran / 4 h / 50 - 55 °C / Inert atmosphere 2.2: 1.5 h / -70 - -60 °C / Inert atmosphere 2.3: -10 - 25 °C 3.1: D-tartaric acid / isopropyl alcohol / 16 h / 30 - 35 °C 3.2: 10 - 15 °C View Scheme

C20H18O8*C28H34BrNO (1135493-18-3) → 4-(benzyloxy)-3-[(1R)-3-(dipropan-2-ylamino)-1-phenylpropyl]benzoic acid (754159-68-7)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium hydroxide / water 2.1: ethyl bromide; iodine; magnesium / tetrahydrofuran / 1 h / 55 °C / Reflux 2.2: 1 h / -65 - -60 °C View Scheme

(-)-N,N-Diisopropyl-3-(2-benzyloxy-5-carboxyphenyl)-3-phenylpropylamine hydrochloride → 4-(benzyloxy)-3-[(1R)-3-(dipropan-2-ylamino)-1-phenylpropyl]benzoic acid (754159-68-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: ammonia / ethyl acetate; water / pH 8 - 9 2: methanol / 50 - 65 °C 3: ammonia / water / pH 8 - 9 View Scheme

(+)-N,N-Diisopropyl-3-(2-benzyloxy-5-carboxyphenyl)-3-phenylpropylamine → 4-(benzyloxy)-3-[(1R)-3-(dipropan-2-ylamino)-1-phenylpropyl]benzoic acid (754159-68-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: methanol / 50 - 65 °C 2: ammonia / water / pH 8 - 9 View Scheme
Stage #1: (+)-N,N-Diisopropyl-3-(2-benzyloxy-5-carboxyphenyl)-3-phenylpropylamine With D-tartaric acid In isopropyl alcohol at 30 - 35℃; for 16h; Stage #2: With water; sodium hydroxide In dichloromethane at 10 - 15℃;

(-)-N,N-diisopropyl-3-(2-benzyloxy-5-carboxyphenyl)-3-phenylpropylamine (-)-di-p-toluoyl-L-tartaric acid (1350477-43-8) → 4-(benzyloxy)-3-[(1R)-3-(dipropan-2-ylamino)-1-phenylpropyl]benzoic acid (754159-68-7)

Conditions	Yield
With ammonia In water pH=8 - 9;

(+)-N,N-diisopropyl-3-(2-benzyloxy-5-carboxyphenyl)-3-phenylpropylamine (760147-33-9) → 4-(benzyloxy)-3-[(1R)-3-(dipropan-2-ylamino)-1-phenylpropyl]benzoic acid (754159-68-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium hydroxide / dimethyl sulfoxide / 5.5 h / 110 - 120 °C 2: methanol / 50 - 65 °C 3: ammonia / water / pH 8 - 9 View Scheme

Cinnamic acid (621-82-9) → 4-(benzyloxy)-3-[(1R)-3-(dipropan-2-ylamino)-1-phenylpropyl]benzoic acid (754159-68-7)

Conditions

Yield

Multi-step reaction with 7 steps 1.1: sulfuric acid / 12 h / 120 - 125 °C 2.1: potassium carbonate; sodium iodide / acetone / 25 - 30 °C 2.2: 5.5 h / 15 °C / Reflux 3.1: sodium bis(2-methoxyethoxy)aluminium dihydride / toluene / 4 h / 5 - 10 °C / Inert atmosphere 4.1: dmap; triethylamine / dichloromethane / 2 h / 0 - 5 °C 5.1: acetonitrile / 32 h / 95 - 100 °C / autoclave; Inert atmosphere 6.1: ethyl bromide; iodine; magnesium / tetrahydrofuran / 4 h / 50 - 55 °C / Inert atmosphere 6.2: 1.5 h / -70 - -60 °C / Inert atmosphere 6.3: -10 - 25 °C 7.1: D-tartaric acid / isopropyl alcohol / 16 h / 30 - 35 °C 7.2: 10 - 15 °C View Scheme

R-(-)3-(2-benzyloxy-5-bromophenyl)-3-phenylpropionic acid (865889-33-4) → 4-(benzyloxy)-3-[(1R)-3-(dipropan-2-ylamino)-1-phenylpropyl]benzoic acid (754159-68-7)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: thionyl chloride; N,N-dimethyl-formamide / toluene / 50 - 55 °C 2.1: toluene / 1 h / 0 - 35 °C 3.1: tetrahydrofuran / 4.5 h / 60 - 65 °C 4.1: iodine; magnesium; ethyl bromide / tetrahydrofuran / 2 h / 60 - 65 °C / Inert atmosphere 4.2: 1 h / -70 - -50 °C View Scheme
Multi-step reaction with 4 steps 1.1: thionyl chloride; N,N-dimethyl-formamide / toluene / 50 - 55 °C 2.1: toluene / 1 h / 0 - 35 °C 3.1: iodine; lithium aluminium tetrahydride / tetrahydrofuran / 2.25 h / 0 - 65 °C 4.1: iodine; magnesium; ethyl bromide / tetrahydrofuran / 2 h / 60 - 65 °C / Inert atmosphere 4.2: 1 h / -70 - -50 °C View Scheme

(3R)-3-[2-(benzyloxy)-5-bromophenyl]-3-phenylpropanoyl chloride (1429299-07-9) → 4-(benzyloxy)-3-[(1R)-3-(dipropan-2-ylamino)-1-phenylpropyl]benzoic acid (754159-68-7)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: toluene / 1 h / 0 - 35 °C 2.1: tetrahydrofuran / 4.5 h / 60 - 65 °C 3.1: iodine; magnesium; ethyl bromide / tetrahydrofuran / 2 h / 60 - 65 °C / Inert atmosphere 3.2: 1 h / -70 - -50 °C View Scheme
Multi-step reaction with 3 steps 1.1: toluene / 1 h / 0 - 35 °C 2.1: iodine; lithium aluminium tetrahydride / tetrahydrofuran / 2.25 h / 0 - 65 °C 3.1: iodine; magnesium; ethyl bromide / tetrahydrofuran / 2 h / 60 - 65 °C / Inert atmosphere 3.2: 1 h / -70 - -50 °C View Scheme

R-(-)-N,N-diisopropyl-3-(2-benzyloxy-5-bromophenyl)-3-phenylpropionamide (1429299-08-0) → 4-(benzyloxy)-3-[(1R)-3-(dipropan-2-ylamino)-1-phenylpropyl]benzoic acid (754159-68-7)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: iodine; lithium aluminium tetrahydride / tetrahydrofuran / 2.25 h / 0 - 65 °C 2.1: iodine; magnesium; ethyl bromide / tetrahydrofuran / 2 h / 60 - 65 °C / Inert atmosphere 2.2: 1 h / -70 - -50 °C View Scheme
Multi-step reaction with 2 steps 1.1: tetrahydrofuran / 4.5 h / 60 - 65 °C 2.1: iodine; magnesium; ethyl bromide / tetrahydrofuran / 2 h / 60 - 65 °C / Inert atmosphere 2.2: 1 h / -70 - -50 °C View Scheme

benzyl chloride (100-44-7) → 4-(benzyloxy)-3-[(1R)-3-(dipropan-2-ylamino)-1-phenylpropyl]benzoic acid (754159-68-7)

Conditions	Yield
Multi-step reaction with 8 steps 1.1: potassium carbonate / 60 - 65 °C 2.1: sodium hydroxide / water / 45 - 50 °C 3.1: ethanol / 5.83 h / 0 - 75 °C 4.1: hydrogenchloride / water; toluene / 1 h / 20 - 25 °C 5.1: thionyl chloride; N,N-dimethyl-formamide / toluene / 50 - 55 °C 6.1: toluene / 1 h / 0 - 35 °C 7.1: tetrahydrofuran / 4.5 h / 60 - 65 °C 8.1: iodine; magnesium; ethyl bromide / tetrahydrofuran / 2 h / 60 - 65 °C / Inert atmosphere 8.2: 1 h / -70 - -50 °C View Scheme
Multi-step reaction with 8 steps 1.1: potassium carbonate / 60 - 65 °C 2.1: sodium hydroxide / water / 45 - 50 °C 3.1: ethanol / 5.83 h / 0 - 75 °C 4.1: hydrogenchloride / water; toluene / 1 h / 20 - 25 °C 5.1: thionyl chloride; N,N-dimethyl-formamide / toluene / 50 - 55 °C 6.1: toluene / 1 h / 0 - 35 °C 7.1: iodine; lithium aluminium tetrahydride / tetrahydrofuran / 2.25 h / 0 - 65 °C 8.1: iodine; magnesium; ethyl bromide / tetrahydrofuran / 2 h / 60 - 65 °C / Inert atmosphere 8.2: 1 h / -70 - -50 °C View Scheme

(+/-)-3-(2-benzyloxy-5-bromophenyl)-3-phenylpropionic acid (1185739-54-1) → 4-(benzyloxy)-3-[(1R)-3-(dipropan-2-ylamino)-1-phenylpropyl]benzoic acid (754159-68-7)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: ethanol / 5.83 h / 0 - 75 °C 2.1: hydrogenchloride / water; toluene / 1 h / 20 - 25 °C 3.1: thionyl chloride; N,N-dimethyl-formamide / toluene / 50 - 55 °C 4.1: toluene / 1 h / 0 - 35 °C 5.1: tetrahydrofuran / 4.5 h / 60 - 65 °C 6.1: iodine; magnesium; ethyl bromide / tetrahydrofuran / 2 h / 60 - 65 °C / Inert atmosphere 6.2: 1 h / -70 - -50 °C View Scheme
Multi-step reaction with 6 steps 1.1: ethanol / 5.83 h / 0 - 75 °C 2.1: hydrogenchloride / water; toluene / 1 h / 20 - 25 °C 3.1: thionyl chloride; N,N-dimethyl-formamide / toluene / 50 - 55 °C 4.1: toluene / 1 h / 0 - 35 °C 5.1: iodine; lithium aluminium tetrahydride / tetrahydrofuran / 2.25 h / 0 - 65 °C 6.1: iodine; magnesium; ethyl bromide / tetrahydrofuran / 2 h / 60 - 65 °C / Inert atmosphere 6.2: 1 h / -70 - -50 °C View Scheme

R-(-)-3-(2-benzyloxy-5-bromophenyl)-3-phenylpropionic acid (1S,2R)-ephedrine salt (1429299-06-8) → 4-(benzyloxy)-3-[(1R)-3-(dipropan-2-ylamino)-1-phenylpropyl]benzoic acid (754159-68-7)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: hydrogenchloride / water; toluene / 1 h / 20 - 25 °C 2.1: thionyl chloride; N,N-dimethyl-formamide / toluene / 50 - 55 °C 3.1: toluene / 1 h / 0 - 35 °C 4.1: tetrahydrofuran / 4.5 h / 60 - 65 °C 5.1: iodine; magnesium; ethyl bromide / tetrahydrofuran / 2 h / 60 - 65 °C / Inert atmosphere 5.2: 1 h / -70 - -50 °C View Scheme
Multi-step reaction with 5 steps 1.1: hydrogenchloride / water; toluene / 1 h / 20 - 25 °C 2.1: thionyl chloride; N,N-dimethyl-formamide / toluene / 50 - 55 °C 3.1: toluene / 1 h / 0 - 35 °C 4.1: iodine; lithium aluminium tetrahydride / tetrahydrofuran / 2.25 h / 0 - 65 °C 5.1: iodine; magnesium; ethyl bromide / tetrahydrofuran / 2 h / 60 - 65 °C / Inert atmosphere 5.2: 1 h / -70 - -50 °C View Scheme

methanol (67-56-1) + 4-(benzyloxy)-3-[(1R)-3-(dipropan-2-ylamino)-1-phenylpropyl]benzoic acid (754159-68-7) → methyl 4-(benzyloxy)-3-[(1R)-3-(dipropan-2-ylamino)-1-phenylpropyl]benzoate (156755-35-0)

Conditions	Yield
With sulfuric acid at 20℃; Product distribution / selectivity; Reflux;
With thionyl chloride at 0 - 65℃;	64 g

4-(benzyloxy)-3-[(1R)-3-(dipropan-2-ylamino)-1-phenylpropyl]benzoic acid (754159-68-7) → (R)-2-[3-(diisopropylamino)-1-phenylpropyl]-4-(hydroxymethyl)-phenol (207679-81-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: sulfuric acid / 20 °C / Reflux 2: sodium bis(2-methoxyethoxy)aluminium dihydride / toluene / 3 h / Inert atmosphere 3: hydrogen / Raney nickel / methanol / 20 °C View Scheme
Multi-step reaction with 2 steps 1.1: sodium bis(2-methoxyethoxy)aluminium dihydride / toluene / 30 - 55 °C 1.2: 0.33 h / 0 - 5 °C 2.1: hydrogen / Raney nickel / methanol / 20 °C View Scheme
Multi-step reaction with 3 steps 1: thionyl chloride / 0 - 65 °C 2: lithium aluminium tetrahydride / tetrahydrofuran / 30 °C 3: hydrogen; palladium 10% on activated carbon / isopropyl alcohol / 25 - 30 °C / 2068.65 - 2585.81 Torr / Autoclave View Scheme

4-(benzyloxy)-3-[(1R)-3-(dipropan-2-ylamino)-1-phenylpropyl]benzoic acid (754159-68-7) → fesoterodine (286930-02-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: sulfuric acid / 20 °C / Reflux 2: sodium bis(2-methoxyethoxy)aluminium dihydride / toluene / 3 h / Inert atmosphere 3: hydrogen / Raney nickel / methanol / 20 °C 4: triethylamine / acetonitrile / -10 °C View Scheme
Multi-step reaction with 3 steps 1.1: sodium bis(2-methoxyethoxy)aluminium dihydride / toluene / 30 - 55 °C 1.2: 0.33 h / 0 - 5 °C 2.1: hydrogen / Raney nickel / methanol / 20 °C 3.1: triethylamine / acetonitrile / -10 °C View Scheme
Multi-step reaction with 4 steps 1: thionyl chloride / 0 - 65 °C 2: lithium aluminium tetrahydride / tetrahydrofuran / 30 °C 3: hydrogen; palladium 10% on activated carbon / isopropyl alcohol / 25 - 30 °C / 2068.65 - 2585.81 Torr / Autoclave 4: sodium hydrogencarbonate / dichloromethane / 3 h / -2 - 3 °C View Scheme

4-(benzyloxy)-3-[(1R)-3-(dipropan-2-ylamino)-1-phenylpropyl]benzoic acid (754159-68-7) → {4-(benzyloxy)-3-[(1R)-3-(dipropan-2-ylamino)-1-phenylpropyl]phenyl}methanol (156755-37-2)

Conditions	Yield
Stage #1: 4-(benzyloxy)-3-[(1R)-3-(dipropan-2-ylamino)-1-phenylpropyl]benzoic acid With sodium bis(2-methoxyethoxy)aluminium dihydride In toluene at 30 - 55℃; Stage #2: With water; sodium hydroxide In toluene at 0 - 5℃; for 0.333333h;
Multi-step reaction with 2 steps 1: sulfuric acid / 20 °C / Reflux 2: sodium bis(2-methoxyethoxy)aluminium dihydride / toluene / 3 h / Inert atmosphere View Scheme

4-(benzyloxy)-3-[(1R)-3-(dipropan-2-ylamino)-1-phenylpropyl]benzoic acid (754159-68-7) → fesoterodine fumarate

Conditions	Yield
Multi-step reaction with 5 steps 1: sulfuric acid / 20 °C / Reflux 2: sodium bis(2-methoxyethoxy)aluminium dihydride / toluene / 3 h / Inert atmosphere 3: hydrogen / Raney nickel / methanol / 20 °C 4: triethylamine / acetonitrile / -10 °C 5: butanone / -5 °C / Heating View Scheme
Multi-step reaction with 4 steps 1.1: sodium bis(2-methoxyethoxy)aluminium dihydride / toluene / 30 - 55 °C 1.2: 0.33 h / 0 - 5 °C 2.1: hydrogen / Raney nickel / methanol / 20 °C 3.1: triethylamine / acetonitrile / -10 °C 4.1: butanone / -5 °C / Heating View Scheme

4-(benzyloxy)-3-[(1R)-3-(dipropan-2-ylamino)-1-phenylpropyl]benzoic acid (754159-68-7) → Tolterodine acid (194482-44-5)

Conditions	Yield
With hydrogen; 5%-palladium/activated carbon In methanol at 25 - 30℃; under 2206.72 - 2942.29 Torr; for 8h; autoclave;

4-(benzyloxy)-3-[(1R)-3-(dipropan-2-ylamino)-1-phenylpropyl]benzoic acid (754159-68-7) → 2-(3-(diisopropylamino)-1-phenylpropyl)-4-(hydroxyl-methyl)phenyl isobutyrate

Conditions	Yield
Multi-step reaction with 3 steps 1.1: hydrogen / 5%-palladium/activated carbon / methanol / 8 h / 25 - 30 °C / 2206.72 - 2942.29 Torr / autoclave 2.1: chloroform / 0.75 h / -45 - -35 °C 3.1: hydrogen / palladium 10% on activated carbon / ethyl acetate / 6 h / 25 - 30 °C / 2206.72 - 2942.29 Torr / autoclave 3.2: 1 h / 0 - 5 °C 3.3: 7.5 h / 0 - 30 °C View Scheme

4-(benzyloxy)-3-[(1R)-3-(dipropan-2-ylamino)-1-phenylpropyl]benzoic acid (754159-68-7) → (R)-3-(3-(diisopropylamino)-1-phenylpropyl)-4-(methacryloyloxy)benzoic acid (1390644-41-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogen / 5%-palladium/activated carbon / methanol / 8 h / 25 - 30 °C / 2206.72 - 2942.29 Torr / autoclave 2: chloroform / 0.75 h / -45 - -35 °C View Scheme

4-(benzyloxy)-3-[(1R)-3-(dipropan-2-ylamino)-1-phenylpropyl]benzoic acid (754159-68-7) → 2-[(1R)-3-(dipropan-2-ylamino)-1-phenylpropyl]-4-(hydroxymethyl)phenyl 2-methylpropanoate fumarate

Conditions	Yield
Multi-step reaction with 5 steps 1: thionyl chloride / 0 - 65 °C 2: lithium aluminium tetrahydride / tetrahydrofuran / 30 °C 3: hydrogen; palladium 10% on activated carbon / isopropyl alcohol / 25 - 30 °C / 2068.65 - 2585.81 Torr / Autoclave 4: sodium hydrogencarbonate / dichloromethane / 3 h / -2 - 3 °C 5: butanone; cyclohexane / 20 - 36 °C View Scheme

Upstream product

• 1429299-06-8 R-(-)-3-(2-benzyloxy-5-bromophenyl)-3-phenylpropionic acid (1S,2R)-ephedrine salt 
• 1185739-54-1 (+/-)-3-(2-benzyloxy-5-bromophenyl)-3-phenylpropionic acid 
• 100-44-7 benzyl chloride 
• 1429299-08-0 R-(-)-N,N-diisopropyl-3-(2-benzyloxy-5-bromophenyl)-3-phenylpropionamide 
• 1429299-07-9 (3R)-3-[2-(benzyloxy)-5-bromophenyl]-3-phenylpropanoyl chloride 
• 865889-33-4 R-(-)3-(2-benzyloxy-5-bromophenyl)-3-phenylpropionic acid 
• 621-82-9 Cinnamic acid 
• 760147-33-9 (+)-N,N-diisopropyl-3-(2-benzyloxy-5-carboxyphenyl)-3-phenylpropylamine 
• 1350477-43-8 (-)-N,N-diisopropyl-3-(2-benzyloxy-5-carboxyphenyl)-3-phenylpropylamine (-)-di-p-toluoyl-L-tartaric acid 
• 701906-29-8 (+)-N,N-Diisopropyl-3-(2-benzyloxy-5-carboxyphenyl)-3-phenylpropylamine 
• 1135493-18-3 C₂₀H₁₈O₈*C₂₈H₃₄BrNO 
• 250214-37-0 (+/-)-toluene-4-sulphonic acid 3-(2-benzyloxy-5-bromophenyl)-3-phenylpropyl ester 
• 156755-24-7 methyl 3-[2-(benzyloxy)-5-bromophenyl]-3-phenylpropanoate 
• 156755-23-6 6-bromo-4-phenyl-3,4-dihydro-2H-chromen-2-one 

Downstream Products

• 156755-35-0 methyl 4-(benzyloxy)-3-[(1R)-3-(dipropan-2-ylamino)-1-phenylpropyl]benzoate 
• 207679-81-0 (R)-2-[3-(diisopropylamino)-1-phenylpropyl]-4-(hydroxymethyl)-phenol 
• 286930-02-7 fesoterodine 
• 156755-37-2 {4-(benzyloxy)-3-[(1R)-3-(dipropan-2-ylamino)-1-phenylpropyl]phenyl}methanol 
• 286930-03-8 fesoterodine fumarate 
• 194482-44-5 Tolterodine acid 
• 250214-44-9 2-(3-(diisopropylamino)-1-phenylpropyl)-4-(hydroxyl-methyl)phenyl isobutyrate 
• 1390644-41-3 (R)-3-(3-(diisopropylamino)-1-phenylpropyl)-4-(methacryloyloxy)benzoic acid 
• 286930-03-8 2-[(1R)-3-(dipropan-2-ylamino)-1-phenylpropyl]-4-(hydroxymethyl)phenyl 2-methylpropanoate fumarate 

Relevant academic research and scientific papers

PROCESS FOR THE PREPARATION OF FESOTERODINE OR ITS SALTS

The present invention relates to a process for the preparation of fesoterodine or its salts.

PROCESS FOR THE PREPARATION OF MUSCARINIC RECEPTOR ANTAGONIST

The present invention relates to novel and improved processes for the preparation of (r)-2-(3-(diisopropylamino)-1-phenylpropyl)-4-(hydroxymethyl)phenylisobutyrate represented by the following structural formula-1 and its pharmaceutically acceptable salts thereof.

IMPROVED PROCESS FOR DIPHENYLPROPYLAMINE DERIVATIVES

The present invention relates to an improved process for the preparation of biologically active diphenylpropylamine derivatives. The present invention specifically relates to an improved fesoterodine of formula (I) and its pharmaceutically acceptable salts.

SOLID STATE FORMS OF FESOTERODINE INTERMEDIATES

Provided herein are novel solid state forms of fesoterodine intermediates, (R)-4-benzyloxy-3-(3-diisopropylamino-1-phenylpropyl)-benzoic acid and (R)-[4-benzyloxy-3-(3-diisopropylamino-1-phenylpropyl)-phenyl]-methanol, and processes for their preparation thereof. The solid state intermediates are useful for preparing fesoterodine or a pharmaceutically acceptable salt thereof in high purity.