1062580-52-2

Basic information

• Product Name: CIS-N-BENZYL-3-METHYLAMINO-4-METHYL-PIPERIDINE BIS-(HYDROCHLORIDE)
• Synonyms: CIS-N-BENZYL-3-METHYLAMINO-4-METHYL-PIPERIDINE BIS-(HYDROCHLORIDE);cis-1-Benzyl-N,4-dimethylpiperidin-3-amine dihydrochloride;cis-1-Benzyl-4-methyl-3-(methylamino)piperidine dihydrochloride 95+%;cis-1-Benzyl-N3,4-dimethylpiperidin-3-amine dihydrochloride;(3R,4R)-1-BENZYL-N,4-DIMETHYLPIPERIDIN-3-AMINE DIHYDROCHLORIDE;(3R,4R)-1-benzyl-N,4-diMethylpiperidin-3-aMine BIS-(HYDROCHLORIDE);(3R,4R)-N,4-Dimethyl-1-(phenylmethyl)-3-piperidinamine hydrochloride;(3R,4R)- cis-1-Benzyl-4-Methyl-3-(MethylaMino)piperidine dihydrochloride
• CAS NO: 1062580-52-2
• Molecular Formula: C₁₄H₂₂N₂*2ClH
• Molecular Weight: 291.25976
• Mol File: 1062580-52-2.mol
• Article Data: 6

Chemical Properties

• Melting Point: 249～251℃
• Appearance: /
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• Solubility: Aqueous Acid (Slightly), DMSO (Slightly, Heated, Sonicated), Methanol (Slightly)
• CAS DataBase Reference: CIS-N-BENZYL-3-METHYLAMINO-4-METHYL-PIPERIDINE BIS-(HYDROCHLORIDE)(CAS DataBase Reference)
• NIST Chemistry Reference: CIS-N-BENZYL-3-METHYLAMINO-4-METHYL-PIPERIDINE BIS-(HYDROCHLORIDE)(1062580-52-2)
• EPA Substance Registry System: CIS-N-BENZYL-3-METHYLAMINO-4-METHYL-PIPERIDINE BIS-(HYDROCHLORIDE)(1062580-52-2)

Safety Data

• HazardClass: IRRITANT
• Hazardous Substances Data: 1062580-52-2(Hazardous Substances Data)

Usage

Description

CIS-N-BENZYL-3-METHYLAMINO-4-METHYL-PIPERIDINE BIS-(HYDROCHLORIDE) is a chemical compound with the molecular formula C16H24N2·2HCl. It is a derivative of piperidine, an organic compound that is a heterocyclic amine. CIS-N-BENZYL-3-METHYLAMINO-4-METHYL-PIPERIDINE BIS-(HYDROCHLORIDE) is characterized by its benzyl and methylamino groups, which contribute to its chemical properties and potential applications.

Uses

Used in Pharmaceutical Industry:
CIS-N-BENZYL-3-METHYLAMINO-4-METHYL-PIPERIDINE BIS-(HYDROCHLORIDE) is used as a pharmaceutical intermediate for the development of various drugs. Its structural features make it a valuable building block in the synthesis of complex molecules with potential therapeutic applications.
Used in Organic Synthesis:
In the field of organic chemistry, CIS-N-BENZYL-3-METHYLAMINO-4-METHYL-PIPERIDINE BIS-(HYDROCHLORIDE) serves as an intermediate in the synthesis of more complex organic compounds. Its unique functional groups can be further modified or reacted to create a wide range of chemical products.
Used in Research and Development:
CIS-N-BENZYL-3-METHYLAMINO-4-METHYL-PIPERIDINE BIS-(HYDROCHLORIDE) is also utilized in laboratory research and development processes. It can be employed to study the effects of its structural features on various chemical and biological properties, potentially leading to the discovery of new drugs or materials.
Used in the Preparation of Janus Kinase Inhibitors:
CIS-N-BENZYL-3-METHYLAMINO-4-METHYL-PIPERIDINE BIS-(HYDROCHLORIDE) is related to the compound (3R,4R)-N,4-Dimethyl-1-(phenylmethyl)-3-piperidinamine Hydrochloride, which is used to prepare Janus kinase 1 (JAK1) selective inhibitors. These inhibitors are important in the treatment of various diseases, including autoimmune disorders and cancer, by targeting the JAK/STAT signaling pathway.

Synthesis

The TiCl4(0.2g, 1mmol), NEt3(0.15g, 1 . 5mmol) suspended 200 ml in toluene, then add 1-benzyl-4-methyl-3-ketone piperidine (20.3g, 100mmol), temperature control 35 °C methylamine solution is added to the reaction solution (9.32g, 120mmol) reaction 4 hours, adding NaBH (OAC) 3 (0.32g, 1 . 5mmol), glacial acetic acid 2 ml, temperature control 35 °C reaction, thin layer monitoring after the reaction is complete. Adding saturated salt water washing, anhydrous sodium sulfate for drying the organic phase, the organic phase concentrated, with residues 35% hydrochloric acid ethanol re-crystallization, to obtain (3R, 4R)-cis-1-benzyl-4-methyl-3-methylamino-piperidine dihydrochloride 17.2g, yield 85.0%, optical purity 99.0% (HPLC method).

InChI:InChI:1S/C14H22N2.2ClH/c1-12-8-9-16(11-14(12)15-2)10-13-6-4-3-5-7-13;;/h3-7,12,14-15H,8-11H2,1-2H3;2*1H

Synthetic route

N-(3R,4R)-(1-benzyl-4-methylpiperidin-3-yl)-methylamine (477600-70-7) → N-((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methylamine dihydrochloride (1062580-52-2)

Conditions	Yield
With hydrogenchloride In ethanol at 0 - 5℃; pH=3 - 4;	94%
With hydrogenchloride In n-heptane; isopropyl alcohol at 20℃; for 0.666667h; Reflux;	60%

1-benzyl-4-methyl-piperidin-3-one (32018-96-5) + methylamine (74-89-5) → N-((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methylamine dihydrochloride (1062580-52-2)

Conditions	Yield
Stage #1: 1-benzyl-4-methyl-piperidin-3-one; methylamine With titanium tetrachloride; triethylamine In tetrahydrofuran at 20℃; for 4h; Stage #2: With sodium tris(acetoxy)borohydride; acetic acid In tetrahydrofuran at 25℃; Stage #3: With hydrogenchloride In ethanol	85%

1-benzyl-4-methyl-piperidin-3-one (32018-96-5) + methylamine acetate (6998-30-7) → N-((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methylamine dihydrochloride (1062580-52-2) + (3R,4R)-1-benzyl-N,4-dimethylpiperidine-3-amine dihydrochloride

Conditions

Yield

Stage #1: 1-benzyl-4-methyl-piperidin-3-one; methylamine acetate With bis(1,5-cyclooctadiene)diiridium(I) dichloride; (S)-3,5-di-tert-butyl-4-methoxyphenyl-(6,6’-dimethoxybiphenyl-2,2’-diyl)-bis(diphenylphosphine); hydrogen In dichloromethane; isopropyl alcohol at 70℃; under 37503.8 Torr; for 18h; Stage #2: With hydrogenchloride In dichloromethane; water; isopropyl alcohol Overall yield = 86%; Overall yield = 498 mg; enantioselective reaction;

A n/a B 74%

(1-benzyl-4-methyl-piperidin-3-yl)-methyl-amine (384338-23-2) → N-((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methylamine dihydrochloride (1062580-52-2) + (3R,4R)-1-benzyl-N,4-dimethylpiperidine-3-amine dihydrochloride

Conditions	Yield
With hydrogenchloride In diethyl ether; acetone for 1h; Inert atmosphere; Overall yield = 498 mg;

1-benzyl-4-methyl-piperidin-3-one (32018-96-5) → N-((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methylamine dihydrochloride (1062580-52-2) + (3R,4R)-1-benzyl-N,4-dimethylpiperidine-3-amine dihydrochloride

Conditions	Yield
Multi-step reaction with 3 steps 1: ethanol / 5 h / 20 °C / Inert atmosphere 2: hydrogen; bis(1,5-cyclooctadiene)diiridium(I) dichloride; (R)-diMe-PipPhos / isopropyl alcohol / 18 h / 20 °C / 37503.8 Torr / Glovebox; Inert atmosphere 3: hydrogenchloride / acetone; diethyl ether / 1 h / Inert atmosphere View Scheme

C14H20N2 → N-((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methylamine dihydrochloride (1062580-52-2) + (3R,4R)-1-benzyl-N,4-dimethylpiperidine-3-amine dihydrochloride

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogen; bis(1,5-cyclooctadiene)diiridium(I) dichloride; (R)-diMe-PipPhos / isopropyl alcohol / 18 h / 20 °C / 37503.8 Torr / Glovebox; Inert atmosphere 2: hydrogenchloride / acetone; diethyl ether / 1 h / Inert atmosphere View Scheme

methyl ((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)carbamate → N-((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methylamine dihydrochloride (1062580-52-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: lithium aluminium tetrahydride / tetrahydrofuran / 2.83 h / 0 °C / Reflux 2: hydrogenchloride / isopropyl alcohol; n-heptane / 0.67 h / 20 °C / Reflux View Scheme

(1-benzyl-4-methyl-1,2,5,6-tetrahydropyridin-3-yl)carbamic acid methyl ester (923036-28-6) → N-((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methylamine dihydrochloride (1062580-52-2)

Conditions

Yield

Multi-step reaction with 3 steps 1: hydrogen; bis(1,5-cyclooctadiene)rhodium(I) trifluoromethanesulfonate; (R)-1-[(Sp)-2-(di-tert-butylphosphino)ferrocenyl]ethylbis(2-methylphenyl)phosphine / 2,2,2-trifluoroethanol / 6 h / 30 - 50 °C / 2625.26 Torr 2: lithium aluminium tetrahydride / tetrahydrofuran / 2.83 h / 0 °C / Reflux 3: hydrogenchloride / isopropyl alcohol; n-heptane / 0.67 h / 20 °C / Reflux View Scheme

3-amino-4-methylpyridine (3430-27-1) → N-((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methylamine dihydrochloride (1062580-52-2)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: dichloromethane; toluene / 10 h / 20 - 25 °C / Large scale 1.2: 70 - 80 °C / Large scale 1.3: 14 h / 10 °C / Large scale 2.1: hydrogenchloride / water; n-heptane / 70 - 75 °C / Large scale 2.2: 0 - 5 °C / Large scale 3.1: Di-p-toluoyl-L-tartaric acid / methanol / 1 h / 50 - 55 °C / Large scale 3.2: 2 h / pH 3 / Large scale View Scheme

N-(1-benzyl-4-methyl-1,2,5,6-tetrahydropyridine-3-yl)acetylamine → N-((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methylamine dihydrochloride (1062580-52-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: hydrogenchloride / water; n-heptane / 70 - 75 °C / Large scale 1.2: 0 - 5 °C / Large scale 2.1: Di-p-toluoyl-L-tartaric acid / methanol / 1 h / 50 - 55 °C / Large scale 2.2: 2 h / pH 3 / Large scale View Scheme

1-benzyl-4-methyl-piperidin-3-one (32018-96-5) → N-((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methylamine dihydrochloride (1062580-52-2)

Conditions	Yield
Stage #1: 1-benzyl-4-methyl-piperidin-3-one With Di-p-toluoyl-L-tartaric acid In methanol at 50 - 55℃; for 1h; Large scale; Stage #2: With hydrogenchloride In methanol; water for 2h; pH=3; Large scale;	1.7 kg

benzyl chloride (100-44-7) → N-((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methylamine dihydrochloride (1062580-52-2)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: dichloromethane; toluene / 10 h / 20 - 25 °C / Large scale 1.2: 70 - 80 °C / Large scale 1.3: 14 h / 10 °C / Large scale 2.1: hydrogenchloride / water; n-heptane / 70 - 75 °C / Large scale 2.2: 0 - 5 °C / Large scale 3.1: Di-p-toluoyl-L-tartaric acid / methanol / 1 h / 50 - 55 °C / Large scale 3.2: 2 h / pH 3 / Large scale View Scheme

N-((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methylamine dihydrochloride (1062580-52-2) + 2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidine (90213-66-4) → (3R,4R)-(1-benzyl-4-methylpiperidin-3-yl)-2-chloro-N-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amine

Conditions	Yield
Stage #1: N-((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methylamine dihydrochloride; 2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidine With potassium carbonate In water at 98 - 102℃; for 10h; Stage #2: at 20 - 25℃; for 4h;	93.6%
With potassium carbonate In water at 90℃; Reagent/catalyst; Solvent; Temperature;	89.5%
With potassium carbonate In water for 10h; Reflux;	82.3%
Stage #1: N-((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methylamine dihydrochloride With potassium carbonate In water Large scale; Stage #2: 2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidine In water at 100℃; Large scale;	4.72 kg

4-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidine (479633-63-1) + N-((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methylamine dihydrochloride (1062580-52-2) → N-((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methyl-(7-p-toluenesulfonyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (923036-30-0)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In water; dimethyl sulfoxide at 107℃; for 9h; Temperature; Large scale;	93%
Stage #1: N-((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methylamine dihydrochloride With potassium carbonate In water Stage #2: 4-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidine In water at 90 - 95℃;	155 g

N-((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methylamine dihydrochloride (1062580-52-2) + C14H10ClN3O2 → C28H31N5O2

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; N,N-dimethyl-formamide at 115 - 120℃; for 12h;	82%

4-chloropyrrolo[3,2-d]pyrimidine + N-((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methylamine dihydrochloride (1062580-52-2) → ((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methyl-(7H-pyrrolo[2,3-d]pyrimidine-4-yl)amine

Conditions	Yield
With potassium carbonate; p-toluenesulfonyl chloride; sodium hydroxide In water; acetone; acetonitrile at 0 - 95℃; for 1h;	77%

N-((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methylamine dihydrochloride (1062580-52-2) + 3,4,6-trichloro-1H-pyrazolo[3,4-d]pyrimidine → N-((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-3,6-dichloro-N-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Conditions	Yield
Stage #1: N-((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methylamine dihydrochloride With N-ethyl-N,N-diisopropylamine In ethanol at 20℃; for 0.166667h; Stage #2: 3,4,6-trichloro-1H-pyrazolo[3,4-d]pyrimidine In ethanol at 100℃; for 2h;	24.9%

N-((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methylamine dihydrochloride (1062580-52-2) + 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1) → ((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methyl-(7H-pyrrolo[2,3-d]pyrimidine-4-yl)amine

Conditions	Yield
With potassium carbonate In water for 24h; Reflux;	0.48%
With potassium carbonate In water at 90℃;	145 g

7-benzyl-2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidine + N-((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methylamine dihydrochloride (1062580-52-2) → C27H30ClN5

Conditions	Yield
With potassium carbonate In ethanol; water Reagent/catalyst; Solvent; Reflux;	280 g

N-((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methylamine dihydrochloride (1062580-52-2) → Tofacitinib citrate

Conditions	Yield
Multi-step reaction with 5 steps 1: N-ethyl-N,N-diisopropylamine / dimethyl sulfoxide; water / 9 h / 107 °C / Large scale 2: sodium hydroxide; water / dimethyl sulfoxide / 1 h / 80 °C / Large scale 3: 10 wt% Pd(OH)2 on carbon; hydrogen / ethanol / 3 h / 61 °C / 760.05 Torr / Large scale 4: 1,8-diazabicyclo[5.4.0]undec-7-ene / ethanol / 1 h / 49 °C / Large scale 5: water / 96 °C / Large scale View Scheme
Multi-step reaction with 3 steps 1: potassium carbonate / water / 10 h / Reflux 2: acetic acid; 5%-palladium/activated carbon; triethylsilane / methanol / 0.17 h / 30 °C 3: 1,8-diazabicyclo[5.4.0]undec-7-ene / butan-1-ol / 0.17 h / 80 °C View Scheme
Multi-step reaction with 4 steps 1: potassium carbonate / water / 90 °C 2: hydrogen; hydrogenchloride; palladium on carbon / water / 120 °C / 2068.65 Torr 3: dichloromethane / -20 °C 4: water; ethanol / 0 °C View Scheme
Multi-step reaction with 4 steps 1: potassium carbonate / water / 90 °C 2: hydrogen; hydrogenchloride; palladium on carbon / water / 120 °C / 2068.65 Torr 3: tetrahydrofuran / 45 °C 4: water; ethanol / 0 °C View Scheme
Multi-step reaction with 4 steps 1: potassium carbonate / water / 90 °C 2: hydrogen; hydrogenchloride; palladium on carbon / water / 120 °C / 2068.65 Torr 3: tetrahydrofuran / 45 °C 4: water; ethanol / 0 °C View Scheme

N-((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methylamine dihydrochloride (1062580-52-2) → ((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methyl-(7H-pyrrolo[2,3-d]pyrimidine-4-yl)amine

Conditions	Yield
Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine / dimethyl sulfoxide; water / 9 h / 107 °C / Large scale 2: sodium hydroxide; water / dimethyl sulfoxide / 1 h / 80 °C / Large scale View Scheme
Multi-step reaction with 2 steps 1.1: potassium carbonate / water 1.2: 90 - 95 °C 2.1: potassium hydroxide; methanol / 40 - 45 °C View Scheme

N-((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methylamine dihydrochloride (1062580-52-2) → ((3R,4R)-4-methylpiperidin-3-yl)-N-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amine dihydrochloride

Conditions	Yield
Multi-step reaction with 3 steps 1: N-ethyl-N,N-diisopropylamine / dimethyl sulfoxide; water / 9 h / 107 °C / Large scale 2: sodium hydroxide; water / dimethyl sulfoxide / 1 h / 80 °C / Large scale 3: 10 wt% Pd(OH)2 on carbon; hydrogen / ethanol / 3 h / 61 °C / 760.05 Torr / Large scale View Scheme

N-((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methylamine dihydrochloride (1062580-52-2) → tasocitinib

Conditions	Yield
Multi-step reaction with 4 steps 1: N-ethyl-N,N-diisopropylamine / dimethyl sulfoxide; water / 9 h / 107 °C / Large scale 2: sodium hydroxide; water / dimethyl sulfoxide / 1 h / 80 °C / Large scale 3: 10 wt% Pd(OH)2 on carbon; hydrogen / ethanol / 3 h / 61 °C / 760.05 Torr / Large scale 4: 1,8-diazabicyclo[5.4.0]undec-7-ene / ethanol / 1 h / 49 °C / Large scale View Scheme
Multi-step reaction with 3 steps 1: potassium carbonate / water / 90 °C 2: acetic acid; 20% palladium hydroxide-activated charcoal; hydrogen / water 3: 1,8-diazabicyclo[5.4.0]undec-7-ene / butan-1-ol View Scheme
Multi-step reaction with 3 steps 1: potassium carbonate / water / 90 °C 2: hydrogen; hydrogenchloride; palladium on carbon / water / 120 °C / 2068.65 Torr 3: dichloromethane / -20 °C View Scheme
Multi-step reaction with 3 steps 1: potassium carbonate / water / 90 °C 2: hydrogen; hydrogenchloride; palladium on carbon / water / 120 °C / 2068.65 Torr 3: tetrahydrofuran / 45 °C View Scheme
Multi-step reaction with 3 steps 1: potassium carbonate / water / 90 °C 2: hydrogen; hydrogenchloride; palladium on carbon / water / 120 °C / 2068.65 Torr 3: tetrahydrofuran / 45 °C View Scheme

N-((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methylamine dihydrochloride (1062580-52-2) → tert-butyl (3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidine-1-carboxylate (477600-74-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium carbonate / water / 24 h / Reflux 2: palladium 10% on activated carbon; hydrogen / methanol / 24 h View Scheme
Multi-step reaction with 2 steps 1: potassium carbonate / water / 10 h / Reflux 2: acetic acid; 5%-palladium/activated carbon; triethylsilane / methanol / 0.17 h / 30 °C View Scheme
Multi-step reaction with 2 steps 1: potassium carbonate / water / 90 °C 2: acetic acid; 20% palladium hydroxide-activated charcoal; hydrogen / water View Scheme
Multi-step reaction with 2 steps 1: potassium carbonate / water / 90 °C 2: hydrogen; hydrogenchloride; palladium on carbon / water / 120 °C / 2068.65 Torr View Scheme
Multi-step reaction with 3 steps 1.1: potassium carbonate / water 1.2: 90 - 95 °C 2.1: potassium hydroxide; methanol / 40 - 45 °C 3.1: hydrogenchloride / water / 20 °C / pH 3.5 - 4.5 3.2: 45 - 50 °C View Scheme

Upstream product

• 384338-23-2 (1-benzyl-4-methyl-piperidin-3-yl)-methyl-amine 
• 32018-96-5 1-benzyl-4-methyl-piperidin-3-one 
• 477600-70-7 N-(3R,4R)-(1-benzyl-4-methylpiperidin-3-yl)-methylamine 
• 923036-28-6 (1-benzyl-4-methyl-1,2,5,6-tetrahydropyridin-3-yl)carbamic acid methyl ester 
• 100-44-7 benzyl chloride 
• 3430-27-1 3-amino-4-methylpyridine 
• 74-89-5 methylamine 
• 6998-30-7 methylamine acetate 

Downstream Products

• 477600-70-7 N-(3R,4R)-(1-benzyl-4-methylpiperidin-3-yl)-methylamine 
• 923036-30-0 N-((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methyl-(7-p-toluenesulfonyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine 
• 540737-29-9 tofacitinib citrate 
• 923036-25-3 (3R,4R)-(1-benzyl-4-methylpiperidin-3-yl)-2-chloro-N-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amine 
• 477600-74-1 tert-butyl (3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidine-1-carboxylate 
• 1259404-17-5 tasocitinib 
• 1260590-51-9 ((3R,4R)-4-methylpiperidin-3-yl)-N-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amine dihydrochloride 
• 540737-29-9 Tofacitinib citrate 

Relevant articles and documents

Asymmetric Synthesis of a Key Intermediate for Tofacitinib via a Dynamic Kinetic Resolution-Reductive Amination Protocol

We report the first example of a catalytic asymmetric reductive amination under dynamic kinetic resolution (DKR) conditions for the preparation of a chiral amine as a key intermediate toward Tofacitinib, an active pharmaceutical ingredient developed by Pfizer. Such a protocol allows the preferential formation of a single product out of four possible diastereomers of the chiral amine starting from the corresponding racemic ketone. The chiral iridium catalyst able to perform such a feast was discovered through a mix of high-throughput screening, racemization study, and reaction optimization.

PROCESS FOR THE PREPARATION OF CHIRAL 3-AMINO-PIPERIDINS, USEFUL INTERMEDIATES FOR THE PREPARATION OF TOFACITINIB

Object of the present invention is an improved process for the preparation of (3R,4R)-1-benzyl-4-methylpiperidin-3-amine by means of chiral Rhodium catalysts.

PROCESS FOR PREPARING CHIRAL AMINES

The invention pertains to a process for the preparation of an amine having at least two chiral centers from a ketone having a chiral center at the a position and an amine comprising the steps of: (a) contacting a ketone having a chiral center at the a position and a primary amine thereby forming an imine; (b) contacting the imine with a reducing agent in the presence of an enantioselective catalyst to form an amine having at least two chiral centers, wherein step (a) and/or step (b) are conducted under racemization-enhancing conditions, wherein the racemization-enhancing conditions are achieved by addition of an acid and/or by addition of a salt of a primary amine and an acid, which salt is added in addition to or instead of the primary amine, and wherein the reducing agent is hydrogen.