79617-96-2

Basic information

• Product Name: Sertraline
• Synonyms: (1s-cis)-1,2,3,4-tetrahydro-4-(3,4-dichlorophenyl)-n-methyl-1-naphthalenamin;1,2,3,4-tetrahydro-4-(3,4-dichlorophenyl)-n-methyl-1-naphthalenamin(1s-cis;cp51974;(1s,4s)-4-(3,4-dichlorophenyl)-n-methyl-1,2,3,4-tetrahydro-1-naphthalenamine;(1s-cis)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-n-methyl-1-naphthalenamine;SERTRALINE;CIS-(1S)(1R)-N-METHYL-4-(3,4-DICHLOROPHENYL)-1,2,3,4-TETRAHYDRO-1- NAPHTHALENAMI;SERTRALINE HYDROCHLORIDE, 99.0+%
• CAS NO: 79617-96-2
• Molecular Formula: C₁₇H₁₇Cl₂N
• Molecular Weight: 306.23
• Product Categories: Amines;(intermediate of sertraline hcl);Sertraline;API
• Mol File: 79617-96-2.mol
• Article Data: 37

Chemical Properties

• Boiling Point: 416.3 °C at 760 mmHg
• Flash Point: 205.6 °C
• Appearance: /
• Density: 1.25 g/cm³
• Vapor Pressure: 8.68E-34mmHg at 25°C
• PKA: pKa 9.48±0.04(H2O I > 0)(Approximate)
• Water Solubility: <0.1g/L(room temperature)
• CAS DataBase Reference: Sertraline(CAS DataBase Reference)
• NIST Chemistry Reference: Sertraline(79617-96-2)
• EPA Substance Registry System: Sertraline(79617-96-2)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• Hazardous Substances Data: 79617-96-2(Hazardous Substances Data)

Usage

Originator

Lustral,Pfizer,UK

Definition

ChEBI: A member of the class of tetralins that is tetralin which is substituted at positions 1 and 4 by a methylamino and a 3,4-dichlorophenyl group, respectively (the S,S diastereoisomer). A selective serotonin-reuptake inhibito (SSRI), it is administered orally as the hydrochloride salt as an antidepressant for the treatment of depression, obsessive-compulsive disorder, panic disorder and post-traumatic stress disorder.

Brand name

Zoloft (Pfizer).

Therapeutic Function

Antidepressant

Biological Functions

Sertraline (Zoloft) has an elimination half-life of 25 hours and can be administered once a day, usually in the morning to avoid insomnia. Sertraline undergoes extensive hepatic metabolism, and doses must be reduced in patients with liver disease. Sertraline may produce more gastrointestinal side effects, such as nausea and diarrhea, than does fluoxetine and is generally thought to be less activating than fluoxetine. It is highly bound to serum proteins (98%) and may alter plasma protein binding of other medications.A 14-day washout period is recommended before starting a MAOI. Sertraline is a weak inhibitor of cytochrome P450 2D6. Intensive therapeutic drug monitoring is indicated when combining sertraline with drugs metabolized by this route that have a narrow therapeutic index, such as the TCAs and the type 1C antiarrhythmics propafenone, encainide, and flecainide.

General Description

Inspection of sertraline (Zoloft) (1S,4S) reveals the pharmacophorefor SERT inhibition. The Cl substituents alsopredict tropism for a 5-HT system. The depicted stereochemistryis important for activity.

Mechanism of action

Sertraline is a potent and selective inhibitor of the neuronal reuptake 5-HT transporter. In vitro binding studies suggest that sertraline has a substantially higher selectivity for inhibiting 5-HT reuptake than other SSRIs or TCAs, including clomipramine. It has only weak effects on neuronal uptake of NE and dopamine. Its mechanism of action is common to the SSRIs. Sertraline is very selective, lacking affinity for other neuroreceptors at therapeutic concentrations.

Pharmacokinetics

Sertraline appears to be slowly but well absorbed from the GI tract following oral administration. The oral bioavailability of sertraline in humans ranges from 20 to 36%, suggesting extensive first-pass metabolism to its N-desmethylated metabolite. Food enhances its oral absorption decreasing the time to achieve peak plasma concentrations from approximately 8 to 6 hours. Following multiple dosing, steady-state plasma sertraline concentrations are proportional and linearly related to dose (half-life: single dose, 24 hours; multiple dose, 24 hours). N-desmethylsertraline, sertraline's principal metabolite, exhibits dose-dependent pharmacokinetics. Sertraline and N-desmethylsertraline are distributed into breast milk. Although in elderly patients the elimination half-life is increased to approximately 36 hours, this effect does not appear to be clinically important and does not warrant dosing alterations. Sertraline is primarily metabolized by CYP3A4 N-demethylation in the intestine and liver to its principal metabolite N-desmethylsertraline and several other metabolites. N-desmethylsertraline is approximately 5- to 10 times less potent as an inhibitor of 5-HT reuptake than sertraline. Sertraline and N-desmethylsertraline undergo further metabolism via oxidative deamination and ring hydroxylation and glucuronide conjugation. N-desmethylsertraline has an elimination half-life approximately 2.5 times that of sertraline. Following oral administration, sertraline and its conjugated metabolites are excreted in both urine and feces, and unmetabolized sertraline accounts for less than 5% of oral dose. Plasma clearance of sertraline was approximately 40% lower in geriatric patients. The elimination half-life of sertraline in patients with hepatic disease was prolonged to a mean of 52 hours, compared with 22 hours in individuals without hepatic disease.

Clinical Use

SSRI: Antidepressant Post-traumatic stress disorder Obsessive compulsive disorder

Drug interactions

Sertraline is not a potent inhibitor of CYP3A4, and because CYP2D6 metabolism is a minor pathway for sertraline, drug–drug interactions with these isoforms is unlikely to be of clinical importance. Sertraline is metabolized by more than one CYP isoform in parallel; therefore, drug interactions or genetic polymorphisms are unlikely to cause clinically significant drug interaction via CYP isoform inhibition. Caution is advised, however, when coadministering sertraline with potential object drugs, especially those with narrow therapeutic indices in elderly patients. For example, sertraline has been shown to reduce the clearance of desipramine and imipramine as a result of CYP2D6 inhibition. Because sertraline is highly protein bound, patients receiving it concurrently with any highly protein-bound drug should be observed for potential adverse effects associated with combined therapy.

Metabolism

Sertraline undergoes extensive first-pass metabolism in the liver. The main pathway is demethylation to inactive N-desmethylsertraline, a process that appears to involve multiple cytochrome P450 isoenzymes; further metabolism and glucuronide conjugation occurs. Sertraline is excreted in about equal amounts in the urine and faeces, mainly as metabolites.

InChI:InChI=1/C25H30N4O9S2.C7H8O3S/c1-24(2)17(29-20(32)16(21(29)39-24)27-19(31)15(26)12-8-6-5-7-9-12)22(33)37-11-38-23(34)18-25(3,4)40(35,36)14-10-13(30)28(14)18;1-6-2-4-7(5-3-6)11(8,9)10/h5-9,14-18,21H,10-11,26H2,1-4H3,(H,27,31);2-5H,1H3,(H,8,9,10)/t14-,15-,16-,17+,18+,21-;/m1./s1

Synthetic route

sertraline hydrochloride (79559-97-0) → Sertraline (79617-96-2)

Conditions	Yield
With sodium hydroxide In water; toluene for 0.25h; pH=> 10;	93%
With sodium hydroxide In water; ethyl acetate	77%
With ammonium hydroxide In water pH=10;
With sodium hydroxide In water
With potassium carbonate In water at 20℃;	10.9 g

[(1S,4S)-4-(3,4-dichloro-phenyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-methyl-amine D(-)mandelate → Sertraline (79617-96-2)

Conditions	Yield
With sodium hydroxide In water; ethyl acetate for 0.25h; pH=> 10;	93%
With sodium hydroxide In water; ethyl acetate for 0.25h; pH=> 10;	93%

benzyl (1S,4S)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl(methyl)carbamate (1346228-89-4) → Sertraline (79617-96-2)

Conditions	Yield
With hydrogen In methanol; dichloromethane; water at 20℃; for 5h; Inert atmosphere;	89%

(4S)-4-(3,4-dichlorophenyl)-1-tetralone (79560-19-3, 79836-44-5, 124379-29-9) + methylamine (74-89-5) → Sertraline (79617-96-2)

Conditions	Yield
With titanium tetrachloride In tetrahydrofuran; diethyl ether; dichloromethane at -78 - 25℃;	88%

cis-(1S,4S)-N-(tert-butoxycarbonyl)-N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthalenamine (267884-85-5) → Sertraline (79617-96-2)

Conditions	Yield
With trifluoroacetic acid In dichloromethane at 20℃; for 1h; deacylation;	85%

C17H16Cl2IN (234448-58-9) → Sertraline (79617-96-2)

Conditions	Yield
With tert.-butyl lithium In tetrahydrofuran; toluene at -78℃;	69%

N-((1S,4S)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)-N-methyl-2-(trimethylsilyl)ethane-1-sulfonamide → Sertraline (79617-96-2)

Conditions	Yield
With cesium fluoride In N,N-dimethyl-formamide at 95℃; for 20h; diastereoselective reaction;	65%

N-methylhydroxyamine hydrochloride (4229-44-1) + (4S)-4-(3,4-dichlorophenyl)-1-tetralone (79560-19-3, 79836-44-5, 124379-29-9) → Sertraline (79617-96-2)

Conditions	Yield
Stage #1: N-methylhydroxyamine hydrochloride; (4S)-4-(3,4-dichlorophenyl)-1-tetralone With sodium acetate In ethanol for 15h; Reflux; Stage #2: With Lindlar's catalyst; hydrogen In methanol; dichloromethane at 20℃; under 760.051 Torr; for 20h;	47%

cis-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-naphthaleneamine (79617-95-1) → Sertraline (79617-96-2)

chloroformic acid ethyl ester (541-41-3) + norsertraline (87857-41-8) → Sertraline (79617-96-2)

Conditions	Yield
With potassium carbonate; lithium (hydro)trimethoxyaluminate 1) MeCN, 2) THF, reflux, 40 h; Yield given. Multistep reaction;

methanol (67-56-1) + C17H14Cl3NO → Sertraline (79617-96-2)

Conditions	Yield
With lithium (hydro)trimethoxyaluminate In tetrahydrofuran for 40h; Reduction; Methylation; Heating;	10 mg

(4-(3,4-dichlorophenyl)-3,4-dihydro-2H-naphthalen-1-ylidene)methylamine (261776-41-4) → trans-(1S,4R)-N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthalenamine (91797-60-3) + Sertraline (79617-96-2) + (4R)-(3,4-Dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenone (155748-61-1)

Conditions	Yield
With (S,S)-(ethylenebis(tetrahydroindenyl))TiF2; phenylsilane In tetrahydrofuran at 20℃; for 24h; kinetic resolution;

N-chloromethylamine (6154-14-9) + 1-(3,4-dichlorophenyl)-1,2-dihydronaphthalene (439134-50-6) → trans-(1R,4S)-N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthalenamine (79951-46-5) + Sertraline (79617-96-2)

Conditions	Yield
Stage #1: 1-(3,4-dichlorophenyl)-1,2-dihydronaphthalene With benzo[1,3,2]dioxaborole; (S)-1-(2-(diphenylphosphanyl)naphthalen-1-yl)isoquinoline In dichloromethane at 20℃; for 12h; Stage #2: With diethylzinc In toluene at 20℃; for 2h; Stage #3: N-chloromethylamine In diethyl ether; water at 0℃; for 0.0833333h; Further stages.;

(S)-N-(4-(3,4-dichlorophenyl)-3,4-dihydronaphthalen-1(2H)-ylidene)methanamine (312620-93-2) → trans-(1R,4S)-N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthalenamine (79951-46-5) + Sertraline (79617-96-2)

Conditions	Yield
With hydrogen; nickel In methanol
With C32H12BF24(1-)*C36H44IrNOP(1+); hydrogen at 20℃; under 15201 Torr; for 12h; optical yield given as %ee; enantioselective reaction;

C18H13Cl2NO3 → Sertraline (79617-96-2)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: magnesium / tetrahydrofuran 1.2: CuBr-SMe2 / 13 / -30 - 0 °C 2.1: sodium tetrahydroborate / tetrahydrofuran; water 3.1: triethylamine 4.1: sodium iodide / acetone / Heating 5.1: tetrahydrofuran 6.1: tert.-butyl lithium / tetrahydrofuran; toluene / -78 °C View Scheme
Multi-step reaction with 6 steps 1.1: magnesium / tetrahydrofuran 1.2: CuBr-SMe2 / 13 / -30 - 0 °C 2.1: sodium tetrahydroborate / tetrahydrofuran; water 3.1: 1H-imidazole; iodine; triphenylphosphine 4.1: hydrogenchloride 5.1: tetrahydrofuran 6.1: tert.-butyl lithium / tetrahydrofuran; toluene / -78 °C View Scheme

C27H25Cl2NO5 → Sertraline (79617-96-2)

Conditions	Yield
Multi-step reaction with 5 steps 1: sodium tetrahydroborate / tetrahydrofuran; water 2: triethylamine 3: sodium iodide / acetone / Heating 4: tetrahydrofuran 5: tert.-butyl lithium / tetrahydrofuran; toluene / -78 °C View Scheme
Multi-step reaction with 5 steps 1: sodium tetrahydroborate / tetrahydrofuran; water 2: 1H-imidazole; iodine; triphenylphosphine 3: hydrogenchloride 4: tetrahydrofuran 5: tert.-butyl lithium / tetrahydrofuran; toluene / -78 °C View Scheme

C18H20Cl2O3 (234448-56-7) → Sertraline (79617-96-2)

Conditions	Yield
Multi-step reaction with 4 steps 1: 1H-imidazole; iodine; triphenylphosphine 2: hydrogenchloride 3: tetrahydrofuran 4: tert.-butyl lithium / tetrahydrofuran; toluene / -78 °C View Scheme
Multi-step reaction with 4 steps 1: triethylamine 2: sodium iodide / acetone / Heating 3: tetrahydrofuran 4: tert.-butyl lithium / tetrahydrofuran; toluene / -78 °C View Scheme

C18H19Cl2IO2 → Sertraline (79617-96-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: hydrogenchloride 2: tetrahydrofuran 3: tert.-butyl lithium / tetrahydrofuran; toluene / -78 °C View Scheme

C19H22Cl2O4S → Sertraline (79617-96-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: NaI / acetone / Heating 2: 100 percent / tetrahydrofuran 3: 69 percent / t-BuLi / tetrahydrofuran; toluene / -78 °C View Scheme

C16H13Cl2IO (234448-57-8) → Sertraline (79617-96-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: tetrahydrofuran 2: tert.-butyl lithium / tetrahydrofuran; toluene / -78 °C View Scheme

o-bromobenzaldehyde dimethyl acetal (35849-09-3) → Sertraline (79617-96-2)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: magnesium / tetrahydrofuran 1.2: CuBr-SMe2 / 13 / -30 - 0 °C 2.1: sodium tetrahydroborate / tetrahydrofuran; water 3.1: triethylamine 4.1: sodium iodide / acetone / Heating 5.1: tetrahydrofuran 6.1: tert.-butyl lithium / tetrahydrofuran; toluene / -78 °C View Scheme
Multi-step reaction with 6 steps 1.1: magnesium / tetrahydrofuran 1.2: CuBr-SMe2 / 13 / -30 - 0 °C 2.1: sodium tetrahydroborate / tetrahydrofuran; water 3.1: 1H-imidazole; iodine; triphenylphosphine 4.1: hydrogenchloride 5.1: tetrahydrofuran 6.1: tert.-butyl lithium / tetrahydrofuran; toluene / -78 °C View Scheme

3,4-Dichlorocinnamic acid (7312-27-8) → Sertraline (79617-96-2)

Conditions	Yield
Multi-step reaction with 7 steps 1.1: pivaloyl chloride; triethylamine; lithium chloride 2.1: magnesium / tetrahydrofuran 2.2: CuBr-SMe2 / 13 / -30 - 0 °C 3.1: sodium tetrahydroborate / tetrahydrofuran; water 4.1: triethylamine 5.1: sodium iodide / acetone / Heating 6.1: tetrahydrofuran 7.1: tert.-butyl lithium / tetrahydrofuran; toluene / -78 °C View Scheme
Multi-step reaction with 7 steps 1.1: pivaloyl chloride; triethylamine; lithium chloride 2.1: magnesium / tetrahydrofuran 2.2: CuBr-SMe2 / 13 / -30 - 0 °C 3.1: sodium tetrahydroborate / tetrahydrofuran; water 4.1: 1H-imidazole; iodine; triphenylphosphine 5.1: hydrogenchloride 6.1: tetrahydrofuran 7.1: tert.-butyl lithium / tetrahydrofuran; toluene / -78 °C View Scheme

ortho-bromobenzaldehyde (6630-33-7) → Sertraline (79617-96-2)

Conditions	Yield
Multi-step reaction with 7 steps 1.1: toluene-4-sulfonic acid / methanol 2.1: magnesium / tetrahydrofuran 2.2: CuBr-SMe2 / 13 / -30 - 0 °C 3.1: sodium tetrahydroborate / tetrahydrofuran; water 4.1: triethylamine 5.1: sodium iodide / acetone / Heating 6.1: tetrahydrofuran 7.1: tert.-butyl lithium / tetrahydrofuran; toluene / -78 °C View Scheme
Multi-step reaction with 7 steps 1.1: toluene-4-sulfonic acid / methanol 2.1: magnesium / tetrahydrofuran 2.2: CuBr-SMe2 / 13 / -30 - 0 °C 3.1: sodium tetrahydroborate / tetrahydrofuran; water 4.1: 1H-imidazole; iodine; triphenylphosphine 5.1: hydrogenchloride 6.1: tetrahydrofuran 7.1: tert.-butyl lithium / tetrahydrofuran; toluene / -78 °C View Scheme

4-(3,4-dichlorophenyl)-3,4-dihydro-2H-naphthalen-1-one (79560-19-3) → Sertraline (79617-96-2)

Conditions	Yield
Multi-step reaction with 4 steps 1: BH3*Me2S / (S)-prolinol core-containing second-generation dendrimer / tetrahydrofuran / 0.8 h 2: PCC / CH2Cl2 / 0 - 20 °C 3: TiCl4 / diethyl ether / -78 - 20 °C 4: H2; Raney-Ni / methanol View Scheme
Multi-step reaction with 2 steps 1: 91 percent / TiCl4 / diethyl ether / -35 - 20 °C 2: (S,S)-(ethylenebis(tetrahydroindenyl))TiF2; PhSiH3 / tetrahydrofuran / 24 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1: TiCl4 / toluene / 17 h / Ambient temperature 2: sodium borohydride / methanol / 1.5 h / Ambient temperature View Scheme

(4S)-4-(3,4-dichlorophenyl)-1-tetralone (79560-19-3, 79836-44-5, 124379-29-9) → Sertraline (79617-96-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: TiCl4 / diethyl ether / -78 - 20 °C 2: H2; Raney-Ni / methanol View Scheme
Multi-step reaction with 4 steps 1: NaBH4 / ethanol 2: 88 percent / dppa, DBU / tetrahydrofuran 3: H2 / Pd-C / ethanol 4: 1) K2CO3, 2) LiAlH(OMe)3 / 1) MeCN, 2) THF, reflux, 40 h View Scheme
Multi-step reaction with 2 steps 1: methanol / 6 h / Reflux 2: sodium tetrahydroborate; methanol View Scheme

(1R,4S)-4-(3,4-dichloro-phenyl)-1,2,3,4-tetrahydro-naphthalen-1-ol (167026-40-6) → Sertraline (79617-96-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: PCC / CH2Cl2 / 0 - 20 °C 2: TiCl4 / diethyl ether / -78 - 20 °C 3: H2; Raney-Ni / methanol View Scheme
Multi-step reaction with 4 steps 1: 88 percent / diphenylphosphorylazide; DBU / tetrahydrofuran / 0 - 20 °C 2: H2 / Pd/C / ethanol / 1 h 3: K2CO3 / acetonitrile / 2 h / Heating 4: 10 mg / LiAlH(OMe)3 / tetrahydrofuran / 40 h / Heating View Scheme
Multi-step reaction with 3 steps 1: 88 percent / dppa, DBU / tetrahydrofuran 2: H2 / Pd-C / ethanol 3: 1) K2CO3, 2) LiAlH(OMe)3 / 1) MeCN, 2) THF, reflux, 40 h View Scheme

1-(3,4-dichlorophenyl)-1,2-dihydronaphthalene (439134-46-0) → Sertraline (79617-96-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: catecholborane / (S)-QUINAP-Rh / toluene / 2 h / 20 °C 1.2: aq. H2O2; flash silica / hexane / 1 h / 0 °C 2.1: catecholborane / (S)-QUINAP-Rh / CH2Cl2 / 12 h / 20 °C 2.2: ZnEt2 / toluene / 2 h / 20 °C 2.3: H2O; diethyl ether / 0.08 h / 0 °C View Scheme

D-dibenzylaminophenylglycinal (174023-92-8) → Sertraline (79617-96-2)

Conditions

Yield

Multi-step reaction with 10 steps 1: 2.62 g / benzene; CH2Cl2 / 15 h / 20 °C 2: 83 percent / Mg / 4 h 3: 76 percent / LiAlH4 / tetrahydrofuran / 0 - 20 °C 4: 0.85 g / pyridinium dichromate / CH2Cl2 / 5 h / 20 °C 5: 1.0 g / tetrahydrofuran / 5 h 6: 78 percent / AlCl3 / CH2Cl2 / 1 h / 20 °C 7: H2 / Pd(OH)2 / methanol / 3 h 8: 0.162 g / methanol / 3 h 9: 84 percent / NaH / tetrahydrofuran / 6 h 10: 85 percent / TFA / CH2Cl2 / 1 h / 20 °C View Scheme

(+)-(2R)-2-[bis(phenylmethyl)amino]-2-phenylethanol (193476-02-7) → Sertraline (79617-96-2)

Conditions

Yield

Multi-step reaction with 11 steps 1: DMSO; oxalyl chloride; Et3N / CH2Cl2 / -78 - 0 °C 2: 2.62 g / benzene; CH2Cl2 / 15 h / 20 °C 3: 83 percent / Mg / 4 h 4: 76 percent / LiAlH4 / tetrahydrofuran / 0 - 20 °C 5: 0.85 g / pyridinium dichromate / CH2Cl2 / 5 h / 20 °C 6: 1.0 g / tetrahydrofuran / 5 h 7: 78 percent / AlCl3 / CH2Cl2 / 1 h / 20 °C 8: H2 / Pd(OH)2 / methanol / 3 h 9: 0.162 g / methanol / 3 h 10: 84 percent / NaH / tetrahydrofuran / 6 h 11: 85 percent / TFA / CH2Cl2 / 1 h / 20 °C View Scheme

norsertraline (87857-41-8) → Sertraline (79617-96-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: 0.162 g / methanol / 3 h 2: 84 percent / NaH / tetrahydrofuran / 6 h 3: 85 percent / TFA / CH2Cl2 / 1 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: K2CO3 / acetonitrile / 2 h / Heating 2: 10 mg / LiAlH(OMe)3 / tetrahydrofuran / 40 h / Heating View Scheme

toluene-4-sulfonic acid (104-15-4) + Sertraline (79617-96-2) → sertraline p-tosylate (630390-72-6)

Conditions	Yield
In ethyl acetate at 20℃;	99%
In tetrahydrofuran

L-tartaric acid (87-69-4, 133-37-9, 147-71-7, 147-73-9, 526-83-0) + Sertraline (79617-96-2) → sertraline L-tartaric acid salt

Conditions	Yield
In ethyl acetate	98%

Sertraline (79617-96-2) + salicylic acid (69-72-7) → sertraline salicylate (928057-22-1)

Conditions	Yield
In ethanol; ethyl acetate at 25 - 30℃; for 5h;	98%

Sertraline (79617-96-2) + acrylonitrile (107-13-1) → 3-(((1S,4S)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)(methyl)amino)propanenitrile

Conditions	Yield
With sodium In methanol at 55℃; for 12h; Inert atmosphere;	98%

Sertraline (79617-96-2) + citric acid (77-92-9) → (1S-cis)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-naphtalenamine citrate (836597-67-2)

Conditions	Yield
In water; ethyl acetate at 0 - 60℃; for 1h; Product distribution / selectivity;	97%
In propan-1-ol; isopropyl alcohol at 0 - 40℃; for 2h; Product distribution / selectivity;	96%

Sertraline (79617-96-2) + (2E)-but-2-enedioic acid (110-17-8) → sertraline fumaric acid salt

Conditions	Yield
In ethyl acetate for 48h;	96%

(-)-camphor-10-sulfonic acid + Sertraline (79617-96-2) → sertraline (-)-camphor-10-sulfonic acid salt

Conditions	Yield
In ethyl acetate at 20℃; for 4h;	96%

Sertraline (79617-96-2) → sertraline hydrochloride (79559-97-0)

Conditions	Yield
With hydrogenchloride In propan-1-ol at 30℃; for 1h; Product distribution / selectivity;	96%
With hydrogenchloride In acetonitrile for 1h; Product distribution / selectivity;	95%
With hydrogenchloride In octanol for 1h; Product distribution / selectivity;	95%

(R)-Mandelic Acid (611-71-2) + Sertraline (79617-96-2) → (cis-1S)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-naphthalenamine (R)-mandelate (244223-89-0, 79617-97-3)

Conditions	Yield
In ethanol Reflux;	94%

Sertraline (79617-96-2) + benzene-1,2-dicarboxylic acid (88-99-3) → sertraline phthalate (928057-20-9)

Conditions	Yield
In ethanol; ethyl acetate at 25 - 30℃; for 5h;	92%

(S)-Mandelic acid (17199-29-0) + Sertraline (79617-96-2) → (1S,4S)-sertraline*(S)-mandelic acid (1357380-69-8)

Conditions	Yield
In ethanol; hexane Reflux;	91%

Sertraline (79617-96-2) + benzenesulfonic acid (98-11-3) → sertraline besylate (630390-70-4)

Conditions	Yield
In ethyl acetate at 20℃;	88%
In ethanol

4-trifluoromethylbenzoic acid (455-24-3) + Sertraline (79617-96-2) → (1S,4S)-4-(3,4-dichlorophenyl)-N-methyl-N-(4-(trifluoromethyl)benzyl)-1,2,3,4-tetrahydronaphthalen-1-amine

Conditions	Yield
With potassium phosphate; 18-crown-6 ether; phenylsilane In tetrahydrofuran at 80℃; for 8h; Glovebox; Molecular sieve; Schlenk technique;	88%

Adipic acid (124-04-9) + Sertraline (79617-96-2) → sertraline adipate (928057-23-2)

Conditions	Yield
In ethyl acetate at 25 - 30℃; for 5h;	86%

Sertraline (79617-96-2) → (S)-1-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalene

Conditions	Yield
With tris(pentafluorophenyl)borate; phenylsilane at 120℃; for 24h; Inert atmosphere; Sealed tube; Glovebox;	85%

tert-butyl ((1H-pyrazol-1-yl)(2,2,2-trifluoroacetamido)methylene)carbamate + Sertraline (79617-96-2) → C23H27Cl2N3O2

Conditions	Yield
Stage #1: tert-butyl ((1H-pyrazol-1-yl)(2,2,2-trifluoroacetamido)methylene)carbamate; Sertraline In tetrahydrofuran at 20℃; Inert atmosphere; Stage #2: With potassium hydrogencarbonate In tetrahydrofuran; methanol Inert atmosphere;	83%

Sertraline (79617-96-2) + acetonitrile (75-05-8) → (1S,4S)-4-(3,4-dichlorophenyl)-N,N-dimethyl-1,2,3,4-tetrahydro naphthalen-1-amine (122873-20-5)

Conditions	Yield
With 18-crown-6 ether; carbon dioxide at 80℃; under 750.075 Torr; for 24h; Inert atmosphere; Schlenk technique; Glovebox;	83%

Sertraline (79617-96-2) + trifluoroacetic acid (76-05-1) → (1S,4S)-4-(3,4-dichlorophenyl)-N-methyl-N-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydronaphthalen-1-amine

Conditions	Yield
With potassium phosphate; 18-crown-6 ether; phenylsilane In tetrahydrofuran at 80℃; for 8h; Glovebox; Molecular sieve; Schlenk technique;	81%

carbon dioxide (124-38-9) + Sertraline (79617-96-2) → N-((1S,4S)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)-N-methylformamide

Conditions	Yield
With cyclopentadienyl iron(II) dicarbonyl dimer; tributylphosphine; phenylsilane In acetonitrile at 30℃; under 760.051 Torr; for 36h; Schlenk technique; Sealed tube;	80%
With phenylsilane; tetrabutyl ammonium fluoride at 20℃; for 4h;	60%

Sertraline (79617-96-2) → (1S-cis )-4-(3,4-dichlorophenyl)-7-iodo-1,2,3,4-tetrahydro-N-methyl-1-naphthalenamine (291306-20-2)

Conditions	Yield
With N-iodo-succinimide; trifluorormethanesulfonic acid In dichloromethane for 23h;	79%

4-methoxybenzoic acid (100-09-4) + Sertraline (79617-96-2) → sertraline 4-methoxybenzoate

Conditions	Yield
In ethanol; ethyl acetate at 25 - 30℃; for 5h;	78%

carbon dioxide (124-38-9) + Sertraline (79617-96-2) → (1S,4S)-4-(3,4-dichlorophenyl)-N,N-dimethyl-1,2,3,4-tetrahydro naphthalen-1-amine (122873-20-5)

Conditions	Yield
With cyclopentadienyl iron(II) dicarbonyl dimer; phenylsilane; triphenylphosphine In acetonitrile at 100℃; under 760.051 Torr; for 24h; Schlenk technique; Sealed tube;	78%
With diphenylsilane; [1,3-bis(2,4,6-trimethylphenyl)imidazol]-2-ylidene In N,N-dimethyl-formamide at 50℃; under 760.051 Torr; chemoselective reaction;	75%

p-Toluic acid (99-94-5) + Sertraline (79617-96-2) → sertraline 4-methylbenzoate (928057-24-3)

Conditions	Yield
In ethanol; ethyl acetate at 25 - 30℃; for 5h;	76%

Glutamic acid (617-65-2) + Sertraline (79617-96-2) → sertraline glutamate

Conditions	Yield
In ethyl acetate at 25 - 30℃; for 5h;	67%

Upstream product

• 541-41-3 chloroformic acid ethyl ester 
• 87857-41-8 norsertraline 
• 79560-20-6 N-[4-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenylidene]methanamine 
• 79617-98-4 (1R,4R)-sertraline 
• 1063723-88-5 (S)-N,N-diisopropylcarbamic acid 1-phenyl-but-3-enyl ester 
• 1338922-77-2 (R)-2-(1-(3,4-dichlorophenyl)-1-phenylbut-3-enyl)-4,4,5,5-tetramethyl-[1,3,2]-dioxaborolane 
• 1338922-76-1 (R)-1,2-dichloro-4-(1-phenylbut-3-enyl)benzene 
• 80735-94-0 1-Phenyl-3-buten-1-ol 
• 77118-87-7 (S)-1-Phenyl-3-buten-1-ol 
• 4229-44-1 N-methylhydroxyamine hydrochloride 
• 124379-29-9 (4S)-4-(3,4-dichlorophenyl)-1-tetralone 
• 100-52-7 benzaldehyde 
• 147189-98-8 (1R)-(3,4-Dichlorophenyl)-1-phenylbutane-4-ol 
• 147255-16-1 (4R)-4-(3,4-dichlorophenyl)-4-phenylbutanoic acid 

Downstream Products

• 630390-69-1 sertraline benzoate 
• 620168-87-8 sertraline hydrochloride acetic acid solvate 
• 836597-67-2 (1S-cis)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-naphtalenamine citrate 
• 928057-24-3 sertraline 4-methylbenzoate 
• 928057-22-1 sertraline salicylate 
• 928057-20-9 sertraline phthalate 
• 261776-41-4 (4-(3,4-dichlorophenyl)-3,4-dihydro-2H-naphthalen-1-ylidene)methylamine 
• 79617-98-4 (1R,4R)-sertraline 
• 91797-60-3 trans-(1S,4R)-N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthalenamine 
• 79951-46-5 trans-(1R,4S)-N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthalenamine 
• 264145-31-5 sertraline mesylate 
• 630403-86-0 sertraline hydrobromide 
• 630390-71-5 sertraline ethanesulfonate 
• 122873-20-5 (1S,4S)-4-(3,4-dichlorophenyl)-N,N-dimethyl-1,2,3,4-tetrahydro naphthalen-1-amine 

Relevant articles and documents

Chemoenzymatic Synthesis of Sertraline

A chemoenzymatic approach has been developed for the preparation of sertraline, an established anti-depressant drug. Ketoreductases (KREDs) were employed to yield a key chiral precursor. The bioreduction of the racemic tetralone exhibited excellent enantioselectivity (>99 % ee) and diastereomeric ratio (99:1) at 29 % conversion (the maximum theoretical yield is 50 %) after 7 hours. The resulting (S,S)-alcohol was efficiently oxidized to an enantiopure (S)-ketone, an immediate precursor of sertraline, by using sodium hypochlorite as oxidant and 2-azaadamantane N-oxyl (AZADO) as organocatalyst. Alternative routes aiming at the direct biocatalytic amination using imine reductases and transaminases were unsuccessful.

New sertraline analogue, preparation method and applications thereof

The invention belongs to the technical field of compounds, preparation methods and applications thereof, and specially relates to a sertraline analogue or a pharmaceutically acceptable salt thereof, wherein the sertraline analogue has a structure represented by the following formula (I), and the compound has good pharmaceutical activity compared with sertraline. The invention further provides a preparation method and applications of the compound represented by the formula (I).

DIPHENYLOXIRANES, PROCESS FOR PREPARATION THEREOF, AND ITS USE IN AN ENANTIOSELECTIVE SYNTHESIS OF (+)-SERTRALINE

The present invention discloses substituted diphenyloxiranes and process for synthesis thereof. The present invention also provides a process for production of enantiomerically pure anti-3,3'-diphenylmethyloxirane and anti-3,3'-diphenylpropan- 1,2-diol from racemic anti-3,3'-diphenylmethyloxirane using hydrolytic kinetic resolution. Further it provides a process for preparation of enantioselective (+)- Sertraline from anti-3,3'-diphenylpropan-1,2-diol.