894-71-3

Basic information

• Product Name: NORTRIPTYLINE HYDROCHLORIDE
• Synonyms: Nortriptyline Hydrochloride (200 mg);Nortriptyline HCl, 1.0 mg/mL as free base;Norzepine;Sensival;Vividyl;NORTRIPTYLINE HCL(P);Norfenazin;Nortriptyline hydrochloride solution
• CAS NO: 894-71-3
• Molecular Formula: C₁₉H₂₁N*ClH
• Molecular Weight: 299.84
• EINECS: 212-973-0
• Product Categories: Amines;Aromatics;Intermediates & Fine Chemicals;Pharmaceuticals;AVENTYL;Biogenic Amine Transport Inhibitors;Biogenic Amine Transport InhibitorsObesity Research;Neurotransmission;Neurotransmission (Obesity);Neurotransmitters;Adrenoceptor
• Mol File: 894-71-3.mol
• Article Data: 0

Chemical Properties

• Melting Point: 217-220?C
• Boiling Point: 403.4°C at 760 mmHg
• Flash Point: 9℃
• Appearance: white to off-white/powder
• Vapor Pressure: 1.02E-06mmHg at 25°C
• Storage Temp.: 2-8°C
• Solubility: ethanol: 100 mg/mL
• Merck: 14,6715
• CAS DataBase Reference: NORTRIPTYLINE HYDROCHLORIDE(CAS DataBase Reference)
• NIST Chemistry Reference: NORTRIPTYLINE HYDROCHLORIDE(894-71-3)
• EPA Substance Registry System: NORTRIPTYLINE HYDROCHLORIDE(894-71-3)

Safety Data

• Hazard Codes: Xn,T,F
• Statements: 22-36/38-23/25-11-39/23/24/25-23/24/25
• Safety Statements: 22-36-45-24-16-7-36/37
• RIDADR: UN 1230 3/PG 2
• WGK Germany: 3
• RTECS: HP0175000
• Hazardous Substances Data: 894-71-3(Hazardous Substances Data)

Usage

Chemical Properties

Off-White Solid

Uses

Nortriptyline Hydrochloride (Amitriptyline EP Impurity C) is a tricyclic antidepressant.

Therapeutic Function

Antidepressant

General Description

Pertinent biological and chemical properties for nortriptyline,3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)Nmethyl-1-propanamine hydrochloride, 5-(3-methyl-aminopropylidene)-10,11-hydro-5H-dibenzo[a,d] cycloheptene hydrochloride(Aventyl, Pamelor), are given previously in thediscussion of amitriptyline. Metabolic inactivation and eliminationare like those of amitriptyline. Nortriptyline is a selectiveNE transporter (NET) inhibitor.

Biological Activity

ki: 3.4 nm: blocks the norepinephrine transporter.ki: 161 nm: inhibits the serotonin transporter.nortriptyline, a dibenzocycloheptene-derivative tricyclic antidepressant, inhibits norepinephrine and serotonin transporters, which is used for short-term treatment of various forms of depression, including major depression, dysthymia, and atypical depressions. nortriptyline suppresses the norepinephrine presynaptic receptors, thus inhibiting the reuptake of this neurotransmitter and increasing the concentration in the synaptic cleft in the central nervous system.norepinephrine transporter is responsible for the sodium-chloride (na+/cl-) -dependent reuptake of extracellular norepinephrine. serotonin transporter transports serotonin from the synaptic cleft to the presynaptic neuron.

Biochem/physiol Actions

Tricyclic antidepressant that is a more potent inhibitor of the norepinephrine transporter (Ki = 3.4 nM) than the serotonin transporter (Ki = 161 nM). 5-HT2 serotonin receptor antagonist.

in vitro

nortriptyline dose-dependently dampened the spontaneous migration of human polymorphonuclear cells (pmn) at the highest concentrations (10-4 and 10-5 m). nortriptyline decreased the motility of the cells at 10-4m. chemotaxis of pmn triggered by 10-10m n-formyl-l-methionil-l-leucyl-l-phenylalanine (fmlp) was blocked by nortriptyline in a dose-dependent fashion [1].

in vivo

rats and mice were injected intraperitoneally with nortriptyline at the dose of 50, 25, 12.5 mg/kg. after 2 hours of the last injection, nortriptyline inducted little or no inhibition of the 4, α-dimethyl-meta-tyramine (h 77/77) induced depletion in a dose of 25 + 12.5 mg/kg. however, there was a partial blockade, evoked by nortriptyline in a dose of 50 + 25 mg/kg, of the h 77/77 elicited depletion in the noradrenaline nerve terminals in all the rats studied. additionally, nortriptyline also proved to be active in the brain, however, its activity was low [2].

references

[1]. sacerdote, p., bianchi, m., & panerai, a. chlorimipramine and nortriptyline but not fluoxetine and fluvoxamine inhibit human polymorphonuclear cell chemotaxis in vitro. general pharmacology: the vascular system. 1994; 25(3): 409-412. [2]. carlsson, a., corrodi, h., fuxe, k., & hkfelt, t. effects of some antidepressant drugs on the depletion of intraneuronal brain catecholamine stores caused by 4, α-dimethyl-meta-tyramine. european journal of pharmacology.1969; 5(4): 367-373.

InChI:InChI=1/C19H21N.ClH/c1-20-14-6-11-19-17-9-4-2-7-15(17)12-13-16-8-3-5-10-18(16)19;/h2-5,7-11,20H,6,12-14H2,1H3;1H

Synthetic route

nortriptyline hydrochloride (894-71-3) + acrylonitrile (107-13-1) → 3-((3-(10,11-dihydro-5H-dibenzo[a,d][7]annulen-5-ylidene)propyl)(methyl)amino)propanenitrile

Conditions	Yield
With sodium In methanol at 55℃; for 12h; Inert atmosphere;	99%

nortriptyline hydrochloride (894-71-3) + tetramethylammonium trifluoromethanethiolate → 3-(10,11-dihydro-5H-dibenzo[a,d][7]annulen-5-ylidene)-N-methyl-N-(trifluoromethyl)propan-1-amine

Conditions	Yield
Stage #1: nortriptyline hydrochloride; tetramethylammonium trifluoromethanethiolate With triethylamine In acetonitrile at 20℃; Stage #2: With silver fluoride In acetonitrile at 50℃; for 4h;	98%

carbon dioxide (124-38-9) + nortriptyline hydrochloride (894-71-3) → (3-(10,11-dihydro-5H-dibenzo[a,d][7]annulen-5-ylidene)propyl)(methyl)carbamic fluoride

Conditions	Yield
With dmap; diethylamino-sulfur trifluoride In acetonitrile at 25℃; under 760.051 Torr; for 2h; Schlenk technique;	92%

N-(tert-butoxycarbonyl)-4-aminobutanoic acid (57294-38-9) + nortriptyline hydrochloride (894-71-3) → tert-butyl 3-((10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5-yllidene)-N-methylcarbamoyl)propylcarbamate (1002331-77-2)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; Industry scale;	88%

nortriptyline hydrochloride (894-71-3) + Bromodiphenylmethane (776-74-9) → N-benzhydryl-3-(10,11-dihydro-5H-dibenzo[a,d][7]annulen-5-ylidene)-N-methylpropan-1-amine

Conditions	Yield
With potassium carbonate In acetonitrile at 100℃; for 12h; Inert atmosphere;	77%

nortriptyline hydrochloride (894-71-3) + p-benzoquinone (106-51-4) → N-Methyl-3-(10,11-dihydro-5H-dibenzocyclohepten-5-yliden)-propylamino-1,4-benzochinon

Conditions	Yield
In dichloromethane for 24h; Ambient temperature;	63%

nortriptyline hydrochloride (894-71-3) + 2,2-difluoroethyl triflate (74427-22-8) → (2,2-difluoro-ethyl)-[3-(10,11-dihydrodibenzo[a,d]cyclohepten-5-ylidene)-propyl]-methyl-amine hydrochloride

Conditions	Yield
Stage #1: nortriptyline hydrochloride With N-ethyl-N,N-diisopropylamine In tetrahydrofuran Reflux; Stage #2: 2,2-difluoroethyl triflate In tetrahydrofuran at 5 - 20℃; for 14h; Stage #3: With hydrogenchloride In diethyl ether at 5℃;	53%

carbon dioxide (1111-72-4) + nortriptyline hydrochloride (894-71-3) → (3-(10,11-dihydro-5H-dibenzo[a,d][7]annulen-5-ylidene)propyl)(methyl)carbamic fluoride [13C]

Conditions	Yield
With dmap; diethylamino-sulfur trifluoride In acetonitrile at 25℃; under 760.051 Torr; for 2h; Schlenk technique;	50%

pyridin-4-yl N,N,N’,N’-tetramethyldiamidophosphate (1224597-89-0) + nortriptyline hydrochloride (894-71-3) → 4-(nortriptyline-N-yl)pyridine

Conditions	Yield
With TurboGrignard In tetrahydrofuran at 0 - 25℃; for 8h; Inert atmosphere;	43%

BOC-glycine (4530-20-5) + nortriptyline hydrochloride (894-71-3) → t-butyl 2-[[3-(10,11-dihydro-5H-dibenzo[a,d][7]annulen-5-ylidene)propyl](methyl)amino]-2-oxoethylcarbamate

Conditions	Yield
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃;	33%
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃;	33%

3-methyl-2-benzothiazolinone hydrazone (1128-67-2) + nortriptyline hydrochloride (894-71-3) → 3-methyl-2-[5-(3-methylamino-propylidene)-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-2-ylazo]-benzothiazol-3-ium

Conditions	Yield
With hydrogenchloride; iron(III) chloride In water at 30℃; for 15h; Condensation;

nortriptyline hydrochloride (894-71-3) → 2,5-Bis-cyclohepten-5-yliden)-propylamino>-1,4-benzochinon

Conditions	Yield
Multi-step reaction with 2 steps 1: 63 percent / CH2Cl2 / 24 h / Ambient temperature 2: 44 percent / CH2Cl2 / Ambient temperature View Scheme

nortriptyline hydrochloride (894-71-3) → nortriptyline-4-aminobutyrate fumarate (1369407-58-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: N-ethyl-N,N-diisopropylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / dichloromethane / 0 - 20 °C / Industry scale 2: methanesulfonic acid / acetic acid tert-butyl ester / 16 h / 30 °C / Industry scale 3: ethanol; water / 25 - 70 °C / Industry scale View Scheme

nortriptyline hydrochloride (894-71-3) → 10,11-dihydro-5-(3-methylamonipropylidene)-5H-dibenzo-[1,4]cycloheptene 4-amino-N-butaneamide (1002404-34-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / dichloromethane / 0 - 20 °C / Industry scale 2: methanesulfonic acid / acetic acid tert-butyl ester / 16 h / 30 °C / Industry scale View Scheme

nortriptyline hydrochloride (894-71-3) + β‐cyclodextrin (7585-39-9) → C42H70O35*C19H21N*ClH

Conditions	Yield
In water at 55℃; for 48h;

nortriptyline hydrochloride (894-71-3) → N-[3-(10,11-Dihydro-dibenzo[a,d]cyclohepten-5-ylidene)-propyl]-N-methyl-hydroxylamine (5253-85-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium / methanol / 12 h / 55 °C / Inert atmosphere 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / -78 °C / Inert atmosphere 3: dichloromethane / 25 °C / Inert atmosphere View Scheme

nortriptyline hydrochloride (894-71-3) → C22H24N2O

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium / methanol / 12 h / 55 °C / Inert atmosphere 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / -78 °C / Inert atmosphere View Scheme

nortriptyline hydrochloride (894-71-3) → O-benzoyl-N-(3-(10,11-dihydro-5H-dibenzo[a,d][7]annulen-5-ylidene)propyl)-N-methylhydroxylamine (5253-86-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: sodium / methanol / 12 h / 55 °C / Inert atmosphere 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / -78 °C / Inert atmosphere 3: dichloromethane / 25 °C / Inert atmosphere 4: triethylamine; dmap / dichloromethane / 0 °C / Inert atmosphere View Scheme

nortriptyline hydrochloride (894-71-3) → N-(3-(10,11-dihydro-5H-dibenzo[a,d][7]annulen-5-ylidene)propyl)-N-methylnaphthalen-1-amine

Conditions	Yield
Multi-step reaction with 5 steps 1: sodium / methanol / 12 h / 55 °C / Inert atmosphere 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / -78 °C / Inert atmosphere 3: dichloromethane / 25 °C / Inert atmosphere 4: triethylamine; dmap / dichloromethane / 0 °C / Inert atmosphere 5: cobalt(II) chloride / tetrahydrofuran / 2 h / 25 °C / Inert atmosphere View Scheme

nortriptyline hydrochloride (894-71-3) → C19H20N(1-)*Cl(1-)*Mg(2+)*ClLi

Conditions	Yield
With isopropyl chloride; magnesium; lithium chloride In tetrahydrofuran at 0 - 25℃; for 0.5h; Inert atmosphere;

nortriptyline hydrochloride (894-71-3) + Bromodiphenylmethane (776-74-9) → C32H29(2)H2N

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium carbonate / acetonitrile / 12 h / 100 °C / Inert atmosphere 2: [(2)H6]acetone; tris(pentafluorophenyl)borate / toluene / 6 h / 150 °C / Inert atmosphere View Scheme

nortriptyline hydrochloride (894-71-3) → 1-(3-((3-(10,11-dihydro-5H-dibenzo[a,d][7]annulen-5-ylidene)propyl)(methyl)amino)propyl)pyrimidin-2(1H)-one

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium hydroxide / water / 20 °C 1.2: 72 h / 20 °C 2.1: triethylamine / tetrahydrofuran / 72 h / 20 °C View Scheme

nortriptyline hydrochloride (894-71-3) + ethylene dibromide (106-93-4) → C21H24BrN

Conditions	Yield
Stage #1: nortriptyline hydrochloride With sodium hydroxide In water at 20℃; Stage #2: ethylene dibromide With triethylamine In tetrahydrofuran at 20℃; for 288h;

nortriptyline hydrochloride (894-71-3) + 1,3-dibromo-propane (109-64-8) → C22H26BrN

Conditions	Yield
Stage #1: nortriptyline hydrochloride With sodium hydroxide In water at 20℃; Stage #2: 1,3-dibromo-propane With triethylamine In tetrahydrofuran at 20℃; for 72h;

Downstream Products

• 5253-86-1 O-benzoyl-N-(3-(10,11-dihydro-5H-dibenzo[a,d][7]annulen-5-ylidene)propyl)-N-methylhydroxylamine