109904-25-8

Basic information

• Product Name: 4,5,6,7-Tetrahydro-5-(triphenylmethyl)thieno[3,2-c]pyridine
• Synonyms: 4,5,6,7-Tetrahydro-5-(triphenylmethyl)thieno[3,2-c]pyridine;5-Trityl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin;4,5,6,7-Tetrahydro-5-tritylthieno[3,2-c]pyridine;5-Trityl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine;5,6,7,7a-Tetrahydro-5-(triphenylMethyl)thieno[3,2-c]pyridine;Thieno[3,2-c]pyridine,4,5,6,7-tetrahydro-5-(triphenylmethyl)-;5-trityl-6,7-dihydro-4H-thieno[3,2-c]pyridine;Zidovudine impurity G
• CAS NO: 109904-25-8
• Molecular Formula: C₂₆H₂₃NS
• Molecular Weight: 381.53
• Product Categories: Aromatics Compounds;Aromatics;Heterocycles;Sulfur & Selenium Compounds
• Mol File: 109904-25-8.mol
• Article Data: 14

Chemical Properties

• Melting Point: 950C
• Appearance: /
• Refractive Index: 1.652
• Storage Temp.: 2-8°C
• Solubility: Chloroform (Slightly), DMSO (Slightly)
• CAS DataBase Reference: 4,5,6,7-Tetrahydro-5-(triphenylmethyl)thieno[3,2-c]pyridine(CAS DataBase Reference)
• NIST Chemistry Reference: 4,5,6,7-Tetrahydro-5-(triphenylmethyl)thieno[3,2-c]pyridine(109904-25-8)
• EPA Substance Registry System: 4,5,6,7-Tetrahydro-5-(triphenylmethyl)thieno[3,2-c]pyridine(109904-25-8)

Safety Data

• Hazardous Substances Data: 109904-25-8(Hazardous Substances Data)

Usage

Chemical Properties

White Solid

Uses

4,5,6,7-Tetrahydro-5-(triphenylmethyl)thieno[3,2-c]pyridine (cas# 109904-25-8) is a compound useful in organic synthesis.

InChI:InChI=1/C26H23NS/c1-4-10-22(11-5-1)26(23-12-6-2-7-13-23,24-14-8-3-9-15-24)27-18-16-25-21(20-27)17-19-28-25/h1-15,17,19H,16,18,20H2

Synthetic route

trityl chloride (76-83-5) + 6,7-dihydro-4H-thieno[3,2-c]pyridine hydrochloride (28783-41-7) → 5-trityl-4,5,6,7-tetrahydro-tieno[3,2-c]pyridine (109904-25-8)

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 2h; Inert atmosphere;	100%
With triethylamine In dichloromethane at 12 - 28℃;	99%
With N-ethyl-N,N-diisopropylamine In acetonitrile for 3h;	94%

4,5,6,7-tetrahydrothieno[3,2-c]pyridine (54903-50-3) + trityl chloride (76-83-5) → 5-trityl-4,5,6,7-tetrahydro-tieno[3,2-c]pyridine (109904-25-8)

Conditions	Yield
With triethylamine In dichloromethane; water	96%
With triethylamine In dichloromethane at 20℃;	96%
With NaH In tetrahydrofuran; ethyl acetate	1.80 g (50%)
With triethylamine In dichloromethane at 0 - 5℃; for 17h; Product distribution / selectivity;

N-trityl-2,4,5,6,7,7a-hexahydrothieno[3,2-c]pyridine (934351-23-2) → 5-trityl-4,5,6,7-tetrahydro-tieno[3,2-c]pyridine (109904-25-8)

Conditions	Yield
With sulfuryl dichloride; triethylamine In dichloromethane at 0℃; for 1h;	66%

N-(tert-butoxycarbonyl)-1,2,5,6-tetrahydropyridine-3-carbaldehyde (406212-52-0) → 5-trityl-4,5,6,7-tetrahydro-tieno[3,2-c]pyridine (109904-25-8)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: CH2Cl2 / 0 - 20 °C 2.1: Et3N / CH2Cl2 / 0 - 20 °C 2.2: 435 mg / CH2Cl2 / 17 h / 20 °C 3.1: n-BuLi / tetrahydrofuran; hexane / -78 - 20 °C 4.1: 217 mg / KSCN; Et3N / methanol; CH2Cl2 / 15 h / 20 °C 5.1: 52 percent / Cu(tfacac)2 / benzene / 24 h / 100 °C 6.1: 66 percent / SO2Cl2; Et3N / CH2Cl2 / 1 h / 0 °C View Scheme

N-trityl-1,2,5,6-tetrahydropyridine-3-carbaldehyde (934351-40-3) → 5-trityl-4,5,6,7-tetrahydro-tieno[3,2-c]pyridine (109904-25-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: n-BuLi / tetrahydrofuran; hexane / -78 - 20 °C 2: 217 mg / KSCN; Et3N / methanol; CH2Cl2 / 15 h / 20 °C 3: 52 percent / Cu(tfacac)2 / benzene / 24 h / 100 °C 4: 66 percent / SO2Cl2; Et3N / CH2Cl2 / 1 h / 0 °C View Scheme

5-oxiranyl-N-trityl-1,2,3,6-tetrahydropyridine (934351-21-0) → 5-trityl-4,5,6,7-tetrahydro-tieno[3,2-c]pyridine (109904-25-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: 217 mg / KSCN; Et3N / methanol; CH2Cl2 / 15 h / 20 °C 2: 52 percent / Cu(tfacac)2 / benzene / 24 h / 100 °C 3: 66 percent / SO2Cl2; Et3N / CH2Cl2 / 1 h / 0 °C View Scheme

5-thiiranyl-N-trityl-1,2,3,6-tetrahydropyridine (934351-22-1) → 5-trityl-4,5,6,7-tetrahydro-tieno[3,2-c]pyridine (109904-25-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 52 percent / Cu(tfacac)2 / benzene / 24 h / 100 °C 2: 66 percent / SO2Cl2; Et3N / CH2Cl2 / 1 h / 0 °C View Scheme

3-formyl-1,2,5,6-tetrahydropyridinium trifluoroacetate → 5-trityl-4,5,6,7-tetrahydro-tieno[3,2-c]pyridine (109904-25-8)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: Et3N / CH2Cl2 / 0 - 20 °C 1.2: 435 mg / CH2Cl2 / 17 h / 20 °C 2.1: n-BuLi / tetrahydrofuran; hexane / -78 - 20 °C 3.1: 217 mg / KSCN; Et3N / methanol; CH2Cl2 / 15 h / 20 °C 4.1: 52 percent / Cu(tfacac)2 / benzene / 24 h / 100 °C 5.1: 66 percent / SO2Cl2; Et3N / CH2Cl2 / 1 h / 0 °C View Scheme

trityl chloride (76-83-5) + sodium benzylate → 5-trityl-4,5,6,7-tetrahydro-tieno[3,2-c]pyridine (109904-25-8)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: Et3N / CH2Cl2 / 0 - 20 °C 1.2: 435 mg / CH2Cl2 / 17 h / 20 °C 2.1: n-BuLi / tetrahydrofuran; hexane / -78 - 20 °C 3.1: 217 mg / KSCN; Et3N / methanol; CH2Cl2 / 15 h / 20 °C 4.1: 52 percent / Cu(tfacac)2 / benzene / 24 h / 100 °C 5.1: 66 percent / SO2Cl2; Et3N / CH2Cl2 / 1 h / 0 °C View Scheme

tert-butyl 5-(hydroxymethyl)-3,6-dihydro-1(2H)-pyridinecarboxylate (126114-07-6) → 5-trityl-4,5,6,7-tetrahydro-tieno[3,2-c]pyridine (109904-25-8)

Conditions

Yield

Multi-step reaction with 7 steps 1.1: 95 percent / MnO2 / CH2Cl2 / 48 h / 20 °C 2.1: CH2Cl2 / 0 - 20 °C 3.1: Et3N / CH2Cl2 / 0 - 20 °C 3.2: 435 mg / CH2Cl2 / 17 h / 20 °C 4.1: n-BuLi / tetrahydrofuran; hexane / -78 - 20 °C 5.1: 217 mg / KSCN; Et3N / methanol; CH2Cl2 / 15 h / 20 °C 6.1: 52 percent / Cu(tfacac)2 / benzene / 24 h / 100 °C 7.1: 66 percent / SO2Cl2; Et3N / CH2Cl2 / 1 h / 0 °C View Scheme

[2-(2-thyenyl)ethyl]amine (30433-91-1) → 5-trityl-4,5,6,7-tetrahydro-tieno[3,2-c]pyridine (109904-25-8)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: dichloromethane / 40 - 45 °C 1.2: 20 - 70 °C 2.1: triethylamine / dichloromethane / 12 - 28 °C View Scheme

5-trityl-4,5,6,7-tetrahydro-tieno[3,2-c]pyridine (109904-25-8) → 5-triphenylmethyl-2-oxo-2,4,5,6,7,7a-hexahydrothieno[3,2-c]pyridine (109904-26-9)

Conditions	Yield
Stage #1: N-trityl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine With n-butyllithium In tetrahydrofuran; hexane; toluene at -5 - 10℃; Stage #2: With Trimethyl borate In tetrahydrofuran; hexane; toluene at -5 - 10℃; Stage #3: With water; dihydrogen peroxide In tetrahydrofuran; hexane; toluene Product distribution / selectivity;	99%
Stage #1: N-trityl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine With n-butyllithium In tetrahydrofuran; hexane at -40 - 10℃; Inert atmosphere; Stage #2: With Triisopropyl borate In tetrahydrofuran; hexane at -40 - 10℃; Inert atmosphere; Stage #3: With dihydrogen peroxide In tetrahydrofuran; hexane at -40 - 20℃; Inert atmosphere;	92%
Stage #1: N-trityl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine With n-butyllithium In tetrahydrofuran; hexane at -40 - 10℃; Inert atmosphere; Stage #2: With Triisopropyl borate In tetrahydrofuran; hexane at -40 - 10℃; Inert atmosphere; Stage #3: With dihydrogen peroxide In tetrahydrofuran; hexane at -40 - 20℃; Inert atmosphere;	92%

5-trityl-4,5,6,7-tetrahydro-tieno[3,2-c]pyridine (109904-25-8) → (5-trityl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)boronic acid (601525-80-8)

Conditions	Yield
Stage #1: N-trityl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine With n-butyllithium In tetrahydrofuran; hexane at -10 - 0℃; for 2h; Inert atmosphere; Stage #2: With Trimethyl borate In tetrahydrofuran; hexane at -10℃; for 1.5h; Stage #3: With sodium hydrogencarbonate In ethyl acetate	96%

5-trityl-4,5,6,7-tetrahydro-tieno[3,2-c]pyridine (109904-25-8) → 5,6,7,7a-tetrahydro-thieno[3,2-c]pyridin-2(4H)-one hydrochloride (115473-15-9)

Conditions	Yield
Stage #1: N-trityl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine With N,N,N,N,-tetramethylethylenediamine; n-hexyllithium In toluene at 0℃; Large scale; Stage #2: With boric acid tributyl ester In toluene at 0℃; for 1h; Large scale; Further stages;	86.1%
Multi-step reaction with 2 steps 1.1: n-butyllithium / tetrahydrofuran / 1 h / 0 - 15 °C / Inert atmosphere 1.2: 1 h / 0 - 15 °C / Inert atmosphere 1.3: 2 h / 0 - 30 °C 2.1: hydrogenchloride; water / acetone / 3 h / 25 - 30 °C View Scheme
Multi-step reaction with 2 steps 1.1: n-butyllithium / toluene; hexane; tetrahydrofuran / -5 - 10 °C 1.2: -5 - 10 °C 2.1: hydrogenchloride / water; acetone / 1 h / 25 - 50 °C View Scheme
Multi-step reaction with 2 steps 1.1: n-butyllithium / tetrahydrofuran / 1 h / 0 - 15 °C / Inert atmosphere 1.2: 1 h / 0 - 15 °C 1.3: 1.75 h / 0 - 30 °C / Reflux 2.1: hydrogenchloride / acetone / 4.5 h / 25 - 30 °C / Reflux View Scheme

5-trityl-4,5,6,7-tetrahydro-tieno[3,2-c]pyridine (109904-25-8) + boric acid tributyl ester (688-74-4) → 5-triphenylmethyl-2-oxo-2,4,5,6,7,7a-hexahydrothieno[3,2-c]pyridine (109904-26-9)

Conditions	Yield
With n-butyllithium In tetrahydrofuran; hexane; water	64%

5-trityl-4,5,6,7-tetrahydro-tieno[3,2-c]pyridine (109904-25-8) → 4,5,6,7-tetrahydrothieno[3,2-c]pyridine (54903-50-3)

Conditions	Yield
With hydrogenchloride In tetrahydrofuran at 20℃; for 1.5h;

5-trityl-4,5,6,7-tetrahydro-tieno[3,2-c]pyridine (109904-25-8) + tributyltin chloride (1461-22-9) → 2-(tributylstannyl)-5-trityl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine

Conditions	Yield
With n-butyllithium In tetrahydrofuran	1.50 g (87%)

5-trityl-4,5,6,7-tetrahydro-tieno[3,2-c]pyridine (109904-25-8) → prasugel (150322-43-3)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: n-butyllithium / tetrahydrofuran / 1 h / 0 - 15 °C / Inert atmosphere 1.2: 1 h / 0 - 15 °C / Inert atmosphere 1.3: 2 h / 0 - 30 °C 2.1: acetone / 0.42 h / 25 - 30 °C 3.1: potassium carbonate / acetonitrile / 0.5 h / 25 - 30 °C 3.2: 7 h / 25 - 30 °C 3.3: 8 h / 0 - 25 °C 4.1: triethylamine / dichloromethane / 0.25 h / 25 - 30 °C 4.2: 6 h / 0 - 5 °C View Scheme
Multi-step reaction with 3 steps 1.1: n-butyllithium / tetrahydrofuran / 1 h / 0 - 15 °C / Inert atmosphere 1.2: 1 h / 0 - 15 °C / Inert atmosphere 1.3: 2 h / 0 - 30 °C 2.1: hydrogenchloride; water / acetone / 3 h / 25 - 30 °C 3.1: potassium carbonate / acetonitrile / 0.5 h / 25 - 30 °C 3.2: 6 h / 25 - 30 °C 3.3: 6.5 h / 0 - 30 °C View Scheme
Multi-step reaction with 4 steps 1.1: n-butyllithium / tetrahydrofuran / 1 h / 0 - 15 °C / Inert atmosphere 1.2: 1 h / 0 - 15 °C / Inert atmosphere 1.3: 2 h / 0 - 30 °C 2.1: acetone / 0.42 h / 25 - 30 °C 3.1: potassium carbonate / acetonitrile / 0.5 h / 25 - 30 °C 3.2: 7 h / 25 - 30 °C 4.1: N-ethyl-N,N-diisopropylamine / acetonitrile / 3.33 h / 10 - 30 °C View Scheme

5-trityl-4,5,6,7-tetrahydro-tieno[3,2-c]pyridine (109904-25-8) → 5-(2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl)-5,6,7,7a-tetrahydrothieno[3,2-c]pyridin-2(4H)-one (150322-38-6)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: n-butyllithium / tetrahydrofuran / 1 h / 0 - 15 °C / Inert atmosphere 1.2: 1 h / 0 - 15 °C / Inert atmosphere 1.3: 2 h / 0 - 30 °C 2.1: acetone / 0.42 h / 25 - 30 °C 3.1: potassium carbonate / acetonitrile / 0.5 h / 25 - 30 °C 3.2: 7 h / 25 - 30 °C 3.3: 8 h / 0 - 25 °C 4.1: sodium hydrogencarbonate / water / 0.5 h / 10 - 15 °C View Scheme
Multi-step reaction with 3 steps 1.1: n-butyllithium / tetrahydrofuran / 1 h / 0 - 15 °C / Inert atmosphere 1.2: 1 h / 0 - 15 °C / Inert atmosphere 1.3: 2 h / 0 - 30 °C 2.1: acetone / 0.42 h / 25 - 30 °C 3.1: potassium carbonate / acetonitrile / 0.5 h / 25 - 30 °C 3.2: 7 h / 25 - 30 °C View Scheme
Multi-step reaction with 3 steps 1.1: n-butyllithium / tetrahydrofuran / 1 h / 0 - 15 °C / Inert atmosphere 1.2: 1 h / 0 - 15 °C / Inert atmosphere 1.3: 2 h / 0 - 30 °C 2.1: hydrogenchloride; water / acetone / 3 h / 25 - 30 °C 3.1: potassium carbonate / acetonitrile / 0.5 h / 25 - 30 °C 3.2: 7 h / 25 - 30 °C View Scheme

5-trityl-4,5,6,7-tetrahydro-tieno[3,2-c]pyridine (109904-25-8) → CS-747 hydrochloride

Conditions	Yield
Multi-step reaction with 5 steps 1.1: n-butyllithium / tetrahydrofuran / 1 h / 0 - 15 °C / Inert atmosphere 1.2: 1 h / 0 - 15 °C / Inert atmosphere 1.3: 2 h / 0 - 30 °C 2.1: acetone / 0.42 h / 25 - 30 °C 3.1: potassium carbonate / acetonitrile / 0.5 h / 25 - 30 °C 3.2: 7 h / 25 - 30 °C 3.3: 8 h / 0 - 25 °C 4.1: triethylamine / dichloromethane / 0.25 h / 25 - 30 °C 4.2: 6 h / 0 - 5 °C 5.1: hydrogenchloride / ethyl acetate; acetone / 0.75 h / 25 - 55 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1.1: n-butyllithium / tetrahydrofuran / 1 h / 0 - 15 °C / Inert atmosphere 1.2: 1 h / 0 - 15 °C / Inert atmosphere 1.3: 2 h / 0 - 30 °C 2.1: hydrogenchloride; water / acetone / 3 h / 25 - 30 °C 3.1: potassium carbonate / acetonitrile / 0.5 h / 25 - 30 °C 3.2: 6 h / 25 - 30 °C 3.3: 6.5 h / 0 - 30 °C 4.1: hydrogenchloride / ethyl acetate; acetone / 0.75 h / 25 - 55 °C / Inert atmosphere View Scheme
Multi-step reaction with 5 steps 1.1: n-butyllithium / tetrahydrofuran / 1 h / 0 - 15 °C / Inert atmosphere 1.2: 1 h / 0 - 15 °C / Inert atmosphere 1.3: 2 h / 0 - 30 °C 2.1: acetone / 0.42 h / 25 - 30 °C 3.1: potassium carbonate / acetonitrile / 0.5 h / 25 - 30 °C 3.2: 7 h / 25 - 30 °C 4.1: N-ethyl-N,N-diisopropylamine / acetonitrile / 3.33 h / 10 - 30 °C 5.1: hydrogenchloride / ethyl acetate; acetone / 0.75 h / 25 - 55 °C / Inert atmosphere View Scheme

5-trityl-4,5,6,7-tetrahydro-tieno[3,2-c]pyridine (109904-25-8) → 5,6,7,7a-tetrahydro-4H-thieno[3,2-c]pyridine-2-one p-toluenesulfonate (952340-39-5)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: n-butyllithium / tetrahydrofuran / 1 h / 0 - 15 °C / Inert atmosphere 1.2: 1 h / 0 - 15 °C / Inert atmosphere 1.3: 2 h / 0 - 30 °C 2.1: acetone / 0.42 h / 25 - 30 °C View Scheme
Multi-step reaction with 2 steps 1.1: n-butyllithium / hexane; tetrahydrofuran / -40 - 10 °C / Inert atmosphere 1.2: -40 - 10 °C / Inert atmosphere 1.3: -40 - 20 °C / Inert atmosphere 2.1: tetrahydrofuran / 0 - 20 °C View Scheme
Multi-step reaction with 2 steps 1.1: n-butyllithium / toluene; hexane; tetrahydrofuran / -5 - 10 °C 1.2: -5 - 10 °C 2.1: tetrahydrofuran / 25 °C View Scheme

5-trityl-4,5,6,7-tetrahydro-tieno[3,2-c]pyridine (109904-25-8) → 5-(α-cyclopropylcarbonyl-2-fluorobenzyl)-2-oxo-2,4,5,6,7,7a-hexahydrothieno[3,2-c]pyridine hydrobromide (1243654-57-0)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: n-butyllithium / tetrahydrofuran / 1 h / 0 - 15 °C / Inert atmosphere 1.2: 1 h / 0 - 15 °C / Inert atmosphere 1.3: 2 h / 0 - 30 °C 2.1: acetone / 0.42 h / 25 - 30 °C 3.1: potassium carbonate / acetonitrile / 0.5 h / 25 - 30 °C 3.2: 7 h / 25 - 30 °C 3.3: 8 h / 0 - 25 °C View Scheme
Multi-step reaction with 4 steps 1.1: n-butyllithium / tetrahydrofuran / 1 h / 0 - 15 °C / Inert atmosphere 1.2: 1 h / 0 - 15 °C / Inert atmosphere 1.3: 2 h / 0 - 30 °C 2.1: acetone / 0.42 h / 25 - 30 °C 3.1: potassium carbonate / acetonitrile / 0.5 h / 25 - 30 °C 3.2: 7 h / 25 - 30 °C 4.1: hydrogen bromide / water; acetone / 1 h / 0 - 5 °C View Scheme
Multi-step reaction with 4 steps 1.1: n-butyllithium / tetrahydrofuran / 1 h / 0 - 15 °C / Inert atmosphere 1.2: 1 h / 0 - 15 °C / Inert atmosphere 1.3: 2 h / 0 - 30 °C 2.1: hydrogenchloride; water / acetone / 3 h / 25 - 30 °C 3.1: potassium carbonate / acetonitrile / 0.5 h / 25 - 30 °C 3.2: 7 h / 25 - 30 °C 4.1: hydrogen bromide / water; acetone / 1 h / 0 - 5 °C View Scheme
Multi-step reaction with 3 steps 1.1: n-butyllithium / tetrahydrofuran / 1 h / 0 - 15 °C / Inert atmosphere 1.2: 1 h / 0 - 15 °C 1.3: 1.75 h / 0 - 30 °C / Reflux 2.1: acetone / 0.92 h / 25 - 30 °C / Reflux 3.1: potassium carbonate / acetonitrile / 7.5 h / 25 - 30 °C 3.2: 8 h / 0 - 25 °C View Scheme

5-trityl-4,5,6,7-tetrahydro-tieno[3,2-c]pyridine (109904-25-8) → 5-(α-cyclopropylcarbonyl-2-fluorobenzyl)-2-oxo-2,4,5,6,7,7a-hexahydro thieno[3,2-c] pyridine hydrochloride (150322-39-7)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: n-butyllithium / tetrahydrofuran / 1 h / 0 - 15 °C / Inert atmosphere 1.2: 1 h / 0 - 15 °C / Inert atmosphere 1.3: 2 h / 0 - 30 °C 2.1: acetone / 0.42 h / 25 - 30 °C 3.1: potassium carbonate / acetonitrile / 0.5 h / 25 - 30 °C 3.2: 7 h / 25 - 30 °C 3.3: 8 h / 0 - 25 °C 4.1: ammonia / dichloromethane; water / 0 - 30 °C 4.2: 1 h / 25 - 30 °C View Scheme
Multi-step reaction with 3 steps 1.1: n-butyllithium / tetrahydrofuran / 1 h / 0 - 15 °C / Inert atmosphere 1.2: 1 h / 0 - 15 °C / Inert atmosphere 1.3: 2 h / 0 - 30 °C 2.1: hydrogenchloride; water / acetone / 3 h / 25 - 30 °C 3.1: potassium carbonate / acetonitrile / 0.5 h / 25 - 30 °C 3.2: 7 h / 25 - 30 °C 3.3: 1 h / 25 - 30 °C View Scheme
Multi-step reaction with 5 steps 1.1: n-butyllithium / tetrahydrofuran / 1 h / 0 - 15 °C / Inert atmosphere 1.2: 1 h / 0 - 15 °C / Inert atmosphere 1.3: 2 h / 0 - 30 °C 2.1: acetone / 0.42 h / 25 - 30 °C 3.1: potassium carbonate / acetonitrile / 0.5 h / 25 - 30 °C 3.2: 7 h / 25 - 30 °C 4.1: hydrogen bromide / water; acetone / 1 h / 0 - 5 °C 5.1: ammonia / dichloromethane; water / 0 - 30 °C 5.2: 1 h / 25 - 30 °C View Scheme

5-trityl-4,5,6,7-tetrahydro-tieno[3,2-c]pyridine (109904-25-8) → 1-cyclopropyl-2-(2-fluorophenyl)-2-(2-hydroxy-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)ethan-1-one

Conditions	Yield
Multi-step reaction with 3 steps 1.1: n-butyllithium / hexane; tetrahydrofuran / -40 - 10 °C / Inert atmosphere 1.2: -40 - 10 °C / Inert atmosphere 1.3: -40 - 20 °C / Inert atmosphere 2.1: tetrahydrofuran / 0 - 20 °C 3.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1.5 h / 20 °C / Cooling with ice View Scheme
Multi-step reaction with 3 steps 1.1: n-butyllithium / hexane; tetrahydrofuran / -40 - 10 °C / Inert atmosphere 1.2: -40 - 10 °C / Inert atmosphere 1.3: -40 - 20 °C / Inert atmosphere 2.1: tetrahydrofuran / 0 - 20 °C 3.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 20 °C / Cooling with ice View Scheme
Multi-step reaction with 4 steps 1.1: n-butyllithium / tetrahydrofuran; hexane / 2 h / -10 - 0 °C / Inert atmosphere 1.2: 1.5 h / -10 °C 2.1: tetrahydrofuran / 0 - 20 °C 3.1: triethylamine / ethanol / 50 °C / Inert atmosphere 3.2: 8 h / 50 °C 4.1: acetic acid / ethanol / 4 °C / Inert atmosphere 4.2: 4 h / 4 - 20 °C View Scheme

5-trityl-4,5,6,7-tetrahydro-tieno[3,2-c]pyridine (109904-25-8) → 2-(tert-butyldimethylsilyloxy)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine

Conditions	Yield
Multi-step reaction with 3 steps 1.1: n-butyllithium / toluene; hexane; tetrahydrofuran / -5 - 10 °C 1.2: -5 - 10 °C 2.1: tetrahydrofuran / 25 °C 3.1: triethylamine / dichloromethane / 0 - 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1.1: n-butyllithium / toluene; hexane; tetrahydrofuran / -5 - 10 °C 1.2: -5 - 10 °C 2.1: hydrogenchloride / water; acetone / 1 h / 25 - 50 °C 3.1: triethylamine / dichloromethane / 0 - 20 °C / Inert atmosphere View Scheme

5-trityl-4,5,6,7-tetrahydro-tieno[3,2-c]pyridine (109904-25-8) → 2-(tert-butyldimethylsilyloxy)-5-(α-cyclopropylformyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine (952340-38-4)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: n-butyllithium / toluene; hexane; tetrahydrofuran / -5 - 10 °C 1.2: -5 - 10 °C 2.1: tetrahydrofuran / 25 °C 3.1: triethylamine / dichloromethane / 0 - 20 °C / Inert atmosphere 4.1: triethylamine / dichloromethane / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1.1: n-butyllithium / toluene; hexane; tetrahydrofuran / -5 - 10 °C 1.2: -5 - 10 °C 2.1: hydrogenchloride / water; acetone / 1 h / 25 - 50 °C 3.1: triethylamine / dichloromethane / 0 - 20 °C / Inert atmosphere 4.1: triethylamine / dichloromethane / 20 °C / Inert atmosphere View Scheme

5-trityl-4,5,6,7-tetrahydro-tieno[3,2-c]pyridine (109904-25-8) → 2-acetoxy-5-[5-chloro-1-(2-fluorophenyl)-2-oxopentyl]-4,5,6,7-tetrahydrothieno[3,2-c]pyridine (1056459-37-0)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: n-butyllithium / hexane; tetrahydrofuran / 0.5 h / -40 - 10 °C / Inert atmosphere 1.2: 1 h / -40 - 10 °C 1.3: 1 h / -40 - 20 °C 2.1: tetrahydrofuran / 6 h / 0 - 20 °C 3.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1.5 h 3.2: 1 h / 15 - 20 °C View Scheme

5-trityl-4,5,6,7-tetrahydro-tieno[3,2-c]pyridine (109904-25-8) → 2-acetoxy-5-[5-bromo-1-(2-fluorophenyl)pentyl]-4,5,6,7-tetrahydro-4H-thieno[3,2-c] pyridine maleate

Conditions	Yield
Multi-step reaction with 4 steps 1.1: n-butyllithium / hexane; tetrahydrofuran / 0.5 h / -40 - 10 °C / Inert atmosphere 1.2: 1 h / -40 - 10 °C 1.3: 1 h / -40 - 20 °C 2.1: tetrahydrofuran / 6 h / 0 - 20 °C 3.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 20 °C 3.2: 1 h / 15 - 20 °C 4.1: acetone View Scheme

5-trityl-4,5,6,7-tetrahydro-tieno[3,2-c]pyridine (109904-25-8) → 2-acetoxy-5-[5-chIoro-1-(2-fluorophenyl)pentyl]-4,5,6,7-tetrahydro-4H-thieno[3,2-c] pyridine maleate

Conditions	Yield
Multi-step reaction with 4 steps 1.1: n-butyllithium / hexane; tetrahydrofuran / 0.5 h / -40 - 10 °C / Inert atmosphere 1.2: 1 h / -40 - 10 °C 1.3: 1 h / -40 - 20 °C 2.1: tetrahydrofuran / 6 h / 0 - 20 °C 3.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1.5 h 3.2: 1 h / 15 - 20 °C 4.1: acetone View Scheme

5-trityl-4,5,6,7-tetrahydro-tieno[3,2-c]pyridine (109904-25-8) → 2-acetoxy-5-[5-bromo-1-(2-fluorophenyl)pentyl]-4,5,6,7-tetrahydro-4H-thieno[3,2-c] pyridine (1373350-59-4)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: n-butyllithium / hexane; tetrahydrofuran / 0.5 h / -40 - 10 °C / Inert atmosphere 1.2: 1 h / -40 - 10 °C 1.3: 1 h / -40 - 20 °C 2.1: tetrahydrofuran / 6 h / 0 - 20 °C 3.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 20 °C 3.2: 1 h / 15 - 20 °C View Scheme

Upstream product

• 76-83-5 trityl chloride 
• 28783-41-7 6,7-dihydro-4H-thieno[3,2-c]pyridine hydrochloride 
• 30433-91-1 [2-(2-thyenyl)ethyl]amine 
• 54903-50-3 4,5,6,7-tetrahydrothieno[3,2-c]pyridine 
• 126114-07-6 tert-butyl 5-(hydroxymethyl)-3,6-dihydro-1(2H)-pyridinecarboxylate 
• 934351-22-1 5-thiiranyl-N-trityl-1,2,3,6-tetrahydropyridine 
• 934351-21-0 5-oxiranyl-N-trityl-1,2,3,6-tetrahydropyridine 
• 934351-40-3 N-trityl-1,2,5,6-tetrahydropyridine-3-carbaldehyde 
• 406212-52-0 N-(tert-butoxycarbonyl)-1,2,5,6-tetrahydropyridine-3-carbaldehyde 
• 934351-23-2 N-trityl-2,4,5,6,7,7a-hexahydrothieno[3,2-c]pyridine 

Downstream Products

• 54903-50-3 4,5,6,7-tetrahydrothieno[3,2-c]pyridine 
• 109904-26-9 5-triphenylmethyl-2-oxo-2,4,5,6,7,7a-hexahydrothieno[3,2-c]pyridine 
• 952340-38-4 2-(tert-butyldimethylsilyloxy)-5-(α-cyclopropylformyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine 
• 601525-80-8 (5-trityl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)boronic acid 
• 1263407-24-4 (5-(2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)boronic acid 
• 1263407-33-5 C₇H₁₀BNO₂S*C₇H₈O₃S 
• 1373350-59-4 2-acetoxy-5-[5-bromo-1-(2-fluorophenyl)pentyl]-4,5,6,7-tetrahydro-4H-thieno[3,2-c] pyridine 
• 1373350-61-8 2-acetoxy-5-[5-chIoro-1-(2-fluorophenyl)pentyl]-4,5,6,7-tetrahydro-4H-thieno[3,2-c] pyridine maleate 
• 1056459-37-0 2-acetoxy-5-[5-chloro-1-(2-fluorophenyl)-2-oxopentyl]-4,5,6,7-tetrahydrothieno[3,2-c]pyridine 
• 150322-39-7 5-(α-cyclopropylcarbonyl-2-fluorobenzyl)-2-oxo-2,4,5,6,7,7a-hexahydro thieno[3,2-c] pyridine hydrochloride 
• 1243654-57-0 5-(α-cyclopropylcarbonyl-2-fluorobenzyl)-2-oxo-2,4,5,6,7,7a-hexahydrothieno[3,2-c]pyridine hydrobromide 
• 952340-39-5 5,6,7,7a-tetrahydro-4H-thieno[3,2-c]pyridine-2-one p-toluenesulfonate 
• 115473-15-9 5,6,7,7a-tetrahydro-thieno[3,2-c]pyridin-2(4H)-one hydrochloride 
• 150322-38-6 5-(2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl)-5,6,7,7a-tetrahydrothieno[3,2-c]pyridin-2(4H)-one 

Relevant articles and documents

Synthesis of Biologically Active Piperidine Metabolites of Clopidogrel: Determination of Structure and Analyte Development

Clopidogrel is a prodrug anticoagulant with active metabolites that irreversibly inhibit the platelet surface GPCR P2Y12 and thus inhibit platelet activation. However, gaining an understanding of patient response has been limited due to imprecise understanding of metabolite activity and stereochemistry, and a lack of acceptable analytes for quantifying in vivo metabolite formation. Methods for the production of all bioactive metabolites of clopidogrel, their stereochemical assignment, and the development of stable analytes via three conceptually orthogonal routes are disclosed. (Chemical Equation Presented).

An improvement to the preparation of prasugrel hydrochloride

An efficient synthesis of prasugrel, a thienopyridine ADP-receptor antagonists, is described. A thienopyridine intermediate was prepared by N-protection, boric acid substitution and N-substitution. After acid hydrolysis of the methyl ether and subsequent acetylation, prasugrel was obtained with a total yield of 50% after seven linear steps from 4,5,6,7-tetrahydrothieno [3,2-c]pyridine and 2-bromo-1-cyclopropyl-2-(2- fluorophenyl)ethan-1-one as raw materials.

METHOD FOR PREPARING PHARMACEUTICALLY ACTIVE INGREDIENT AND INTERMEDIATES THEREOF

The present invention is related to a safe and industrially applicable method for the preparation of 2-acetoxy-5-(2-fluoro-α-cyclopropyl- carbonyl-benzyl)-4,5,6,7-tetrahydro-4H-thieno[3,2-c]pyridine in a quality suitable for use as pharmaceutically active ingredient wherein the concentration of the impurities of the Formula.(XXIV) or (XXIVa) is reduced.