274693-55-9

Basic information

• Product Name: 1-Acetyladamantane Intermediate
• Synonyms: 2-((3aS,4R,6S,6aS)-6-aMino-2,2-diMethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)oxy)ethanol;Ethanol, 2-[[(3aR,4S,6R,6aS)-6-aMinotetrahydro-2,2-diMethyl-4H-cyclopenta-1,3-dioxol-4-yl]oxy]-;2-(((3aR,4S,6R,6aS)-6-AMino-2,2-diMethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)oxy)ethanol/Ticargrelor Inter Ⅲ;Ticagrelor Related Compound I;2-(((3aR,4S,6R,6aS);-6-Amino-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl);1-Acetyladamantane Intermediate;2-(6-Amino-2,2-dimethyl-tetrahydro-cyclopenta[1,3]dioxol-4-yloxy)-ethanol
• CAS NO: 274693-55-9
• Molecular Formula: C₁₀H₁₉NO₄
• Molecular Weight: 217.26216
• EINECS: 1312995-182-4
• Mol File: 274693-55-9.mol

Chemical Properties

• Boiling Point: 338℃
• Flash Point: 158℃
• Appearance: /
• Density: 1.21
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.52
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• PKA: 14.33±0.10(Predicted)
• CAS DataBase Reference: 1-Acetyladamantane Intermediate(CAS DataBase Reference)
• NIST Chemistry Reference: 1-Acetyladamantane Intermediate(274693-55-9)
• EPA Substance Registry System: 1-Acetyladamantane Intermediate(274693-55-9)

Safety Data

• Hazardous Substances Data: 274693-55-9(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
1-Acetyladamantane Intermediate is used as an intermediate in the synthesis of orally active reversible P2Y12 receptor antagonists. These antagonists play a vital role in the prevention of thrombosis, a medical condition characterized by the formation of blood clots within the circulatory system. The intermediate's structural properties enable the development of effective and targeted therapeutic agents for treating thrombosis and related cardiovascular diseases.

InChI:InChI=1/C10H19NO4/c1-10(2)14-8-6(11)5-7(9(8)15-10)13-4-3-12/h6-9,12H,3-5,11H2,1-2H3/t6-,7+,8+,9-/m1/s1

Synthetic route

benzyl 6-(2-hydroxyethoxy)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-ylcarbamate (274693-54-8) → [3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9)

Conditions	Yield
With hydrogen; palladium on activated charcoal In ethanol	99%
With 5%-palladium/activated carbon In methanol at 20℃; for 1h;	75.7%
palladium on charcoal In ethanol

C17H25NO4 → [3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9)

Conditions	Yield
With palladium on activated charcoal; hydrogen In ethanol at 50 - 60℃; under 750.075 Torr; for 12h; Autoclave; Inert atmosphere;	98%
With palladium on activated charcoal; hydrogen; acetic acid In methanol at 20℃; under 3750.38 - 6000.6 Torr; for 10h;	92.8%

C10H16O5 → [3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9)

Conditions	Yield
With hydrogenchloride; pyridoxal 5'-phosphate; isopropylamine; triethylamine In water at 25℃; for 16h; pH=8; Solvent; Reagent/catalyst; Temperature; Large scale; Enzymatic reaction;	97%

C15H27NO6 → [3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9)

Conditions	Yield
In ethylene glycol at 120℃; for 8h; Solvent; Temperature;	92%

C17H24N2O6 → [3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9)

Conditions	Yield
With palladium on activated charcoal; hydrogen; acetic acid In methanol at 20℃; for 14h;	91.5%

(3aS,4R,6S,6aR)-N-benzyl-6-(2-(benzyloxy)ethoxy)-2,2-dimethyl-tetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-amine (1444301-50-1) → [3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol at 40℃; under 7500.75 Torr; for 168h;	63%

N-(((4S,5R)-2,2-dimethyl-5-vinyl-1 ,3-dioxolan-4-yl)methylene)-1-phenylmethanamine oxide (345898-95-5) → [3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: N,N-dimethyl-formamide; toluene / 5 h / 110 °C 2.1: palladium 10% on activated carbon; hydrogen / methanol / 14 h / 20 °C 3.1: N-ethyl-N,N-diisopropylamine / 4-methyl-2-pentanone / 2 h / 20 °C 4.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / -30 °C 4.2: 3 h / 20 °C 5.1: lithium borohydride / tetrahydrofuran / 5 h / 0 °C 6.1: 5%-palladium/activated carbon / methanol / 1 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: toluene / 5 h / Reflux 2.1: zinc; acetic acid / diethyl ether / 72.48 h / 0 - 25 °C 3.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 0 °C / Inert atmosphere 3.2: 4 h / 0 - 20 °C / Inert atmosphere 4.1: palladium 10% on activated carbon; hydrogen / methanol / 168 h / 40 °C / 7500.75 Torr View Scheme
Multi-step reaction with 6 steps 1.1: N,N-dimethyl-formamide / 2 h / Reflux 2.1: ammonium formate; palladium 10% on activated carbon / methanol / 1.5 h / Reflux 3.1: potassium carbonate / water / 5.5 h / 20 °C 4.1: sodium hydride / N,N-dimethyl-formamide / 1 h / -20 °C 4.2: 6.33 h / -20 - 20 °C 5.1: sodium tetrahydroborate; ethanol / 4 h / 60 °C 6.1: ammonium formate; palladium 10% on activated carbon / ethanol / 1 h / 40 °C View Scheme

ethyl 2-(6-(benzyloxycarbonylamino)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yloxy) acetate → [3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: lithium borohydride / tetrahydrofuran / 5 h / 0 °C 2: 5%-palladium/activated carbon / methanol / 1 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1.1: lithium borohydride / tetrahydrofuran / 0 - 20 °C 1.2: 20 °C 1.3: pH 6 - 7 2.1: ammonium formate / palladium 10% on activated carbon / ethanol / 30 - 70 °C View Scheme

[3aS-(3aα,4α,6α,6aα)]-(tetrahydro-6-hydroxy-2,2-dimethyl-4H-cyclopenta-1,3-dioxol-4-yl)carbamic acid phenylmethyl ester (274693-53-7) → [3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / -30 °C 1.2: 3 h / 20 °C 2.1: lithium borohydride / tetrahydrofuran / 5 h / 0 °C 3.1: 5%-palladium/activated carbon / methanol / 1 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: potassium tert-butylate / tetrahydrofuran / 0 °C 2.1: lithium borohydride / tetrahydrofuran / 0 - 20 °C 2.2: 20 °C 2.3: pH 6 - 7 3.1: ammonium formate / palladium 10% on activated carbon / ethanol / 30 - 70 °C View Scheme
Multi-step reaction with 2 steps 1: potassium tert-butylate 2: hydrogen / palladium on activated charcoal / ethanol View Scheme
Multi-step reaction with 3 steps 1.1: sodium hydride / N,N-dimethyl-formamide / 1 h / -20 °C 1.2: 6.33 h / -20 - 20 °C 2.1: sodium tetrahydroborate; ethanol / 4 h / 60 °C 3.1: ammonium formate; palladium 10% on activated carbon / ethanol / 1 h / 40 °C View Scheme

methyl 2,3-O-isopropylidene-D-ribofuranoside (4099-85-8, 5531-21-5, 20672-63-3, 20672-65-5, 58763-00-1, 63029-07-2, 72402-14-3, 84894-45-1, 129263-68-9) → [3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9)

Conditions	Yield
Multi-step reaction with 10 steps 1.1: pyridine / 24 h / 20 °C 2.1: sodium iodide / butanone / 24 h / 120 °C 3.1: zinc / ethanol / 1 h / 70 °C 4.1: sodium carbonate / ethanol / 1 h / 50 °C 5.1: N,N-dimethyl-formamide; toluene / 5 h / 110 °C 6.1: palladium 10% on activated carbon; hydrogen / methanol / 14 h / 20 °C 7.1: N-ethyl-N,N-diisopropylamine / 4-methyl-2-pentanone / 2 h / 20 °C 8.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / -30 °C 8.2: 3 h / 20 °C 9.1: lithium borohydride / tetrahydrofuran / 5 h / 0 °C 10.1: 5%-palladium/activated carbon / methanol / 1 h / 20 °C View Scheme
Multi-step reaction with 8 steps 1.1: pyridine / 4 h / -10 - -5 °C 2.1: lithium bromide / butanone / 22 h / 80 °C 3.1: hydrogenchloride; zinc/copper couple / water; methanol / 18 h / 25 °C 4.1: sodium carbonate / methanol / 0.5 h / 25 °C 5.1: toluene / 5 h / Reflux 6.1: zinc; acetic acid / diethyl ether / 72.48 h / 0 - 25 °C 7.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 0 °C / Inert atmosphere 7.2: 4 h / 0 - 20 °C / Inert atmosphere 8.1: palladium 10% on activated carbon; hydrogen / methanol / 168 h / 40 °C / 7500.75 Torr View Scheme

D-Ribose (532-20-7, 613-83-2, 7261-25-8, 7687-39-0, 13221-22-2, 14795-83-6, 15761-67-8, 20074-49-1, 25545-03-3, 25545-04-4, 32445-75-3, 34436-17-4, 36441-93-7, 36468-53-8, 37110-85-3, 37388-49-1, 38029-69-5, 40461-77-6, 40461-89-0, 41546-19-4, 41546-20-7, 41546-21-8, 41546-26-3, 41546-29-6, 41546-30-9, 41546-31-0, 126872-16-0, 131064-98-7) → [3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9)

Conditions

Yield

Multi-step reaction with 11 steps 1.1: perchloric acid / acetone / 24 h / Molecular sieve 2.1: pyridine / 24 h / 20 °C 3.1: sodium iodide / butanone / 24 h / 120 °C 4.1: zinc / ethanol / 1 h / 70 °C 5.1: sodium carbonate / ethanol / 1 h / 50 °C 6.1: N,N-dimethyl-formamide; toluene / 5 h / 110 °C 7.1: palladium 10% on activated carbon; hydrogen / methanol / 14 h / 20 °C 8.1: N-ethyl-N,N-diisopropylamine / 4-methyl-2-pentanone / 2 h / 20 °C 9.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / -30 °C 9.2: 3 h / 20 °C 10.1: lithium borohydride / tetrahydrofuran / 5 h / 0 °C 11.1: 5%-palladium/activated carbon / methanol / 1 h / 20 °C View Scheme

((3aR,4R,6aR)-6-methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl 4-methylbenzenesulfonate (4137-56-8, 5531-22-6, 6953-71-5, 52631-00-2, 63087-95-6, 84894-43-9, 13007-50-6) → [3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9)

Conditions	Yield
Multi-step reaction with 9 steps 1.1: sodium iodide / butanone / 24 h / 120 °C 2.1: zinc / ethanol / 1 h / 70 °C 3.1: sodium carbonate / ethanol / 1 h / 50 °C 4.1: N,N-dimethyl-formamide; toluene / 5 h / 110 °C 5.1: palladium 10% on activated carbon; hydrogen / methanol / 14 h / 20 °C 6.1: N-ethyl-N,N-diisopropylamine / 4-methyl-2-pentanone / 2 h / 20 °C 7.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / -30 °C 7.2: 3 h / 20 °C 8.1: lithium borohydride / tetrahydrofuran / 5 h / 0 °C 9.1: 5%-palladium/activated carbon / methanol / 1 h / 20 °C View Scheme
Multi-step reaction with 7 steps 1.1: lithium bromide / butanone / 22 h / 80 °C 2.1: hydrogenchloride; zinc/copper couple / water; methanol / 18 h / 25 °C 3.1: sodium carbonate / methanol / 0.5 h / 25 °C 4.1: toluene / 5 h / Reflux 5.1: zinc; acetic acid / diethyl ether / 72.48 h / 0 - 25 °C 6.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 0 °C / Inert atmosphere 6.2: 4 h / 0 - 20 °C / Inert atmosphere 7.1: palladium 10% on activated carbon; hydrogen / methanol / 168 h / 40 °C / 7500.75 Torr View Scheme

(4R,5R)-2,2-dimethyl-5-vinyl-[1,3]dioxolane-4-carbaldehyde (155934-55-7) → [3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9)

Conditions	Yield
Multi-step reaction with 7 steps 1.1: sodium carbonate / ethanol / 1 h / 50 °C 2.1: N,N-dimethyl-formamide; toluene / 5 h / 110 °C 3.1: palladium 10% on activated carbon; hydrogen / methanol / 14 h / 20 °C 4.1: N-ethyl-N,N-diisopropylamine / 4-methyl-2-pentanone / 2 h / 20 °C 5.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / -30 °C 5.2: 3 h / 20 °C 6.1: lithium borohydride / tetrahydrofuran / 5 h / 0 °C 7.1: 5%-palladium/activated carbon / methanol / 1 h / 20 °C View Scheme
Multi-step reaction with 5 steps 1.1: sodium carbonate / methanol / 0.5 h / 25 °C 2.1: toluene / 5 h / Reflux 3.1: zinc; acetic acid / diethyl ether / 72.48 h / 0 - 25 °C 4.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 0 °C / Inert atmosphere 4.2: 4 h / 0 - 20 °C / Inert atmosphere 5.1: palladium 10% on activated carbon; hydrogen / methanol / 168 h / 40 °C / 7500.75 Torr View Scheme

(3aR,4S,6R,6aS)-6-amino-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-ol (155899-66-4) → [3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: N-ethyl-N,N-diisopropylamine / 4-methyl-2-pentanone / 2 h / 20 °C 2.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / -30 °C 2.2: 3 h / 20 °C 3.1: lithium borohydride / tetrahydrofuran / 5 h / 0 °C 4.1: 5%-palladium/activated carbon / methanol / 1 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: potassium carbonate / ethanol; water / 3 h / 60 - 65 °C 1.2: 0.25 h 2.1: sodium t-butanolate / N,N-dimethyl-formamide; tetrahydrofuran / 2 h / -10 - 5 °C 3.1: diisobutylaluminium hydride / toluene / 2.5 h / -25 - -20 °C 3.2: 0.25 h 4.1: hydrogen / 20% palladium hydroxide-activated charcoal / methanol / 10 h / 20 - 25 °C / 2327.23 Torr / Autoclave; Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1.1: sodium carbonate / water; 4-methyl-2-pentanone / 20 °C 2.1: potassium tert-butylate / tetrahydrofuran / 0 °C 3.1: lithium borohydride / tetrahydrofuran / 0 - 20 °C 3.2: 20 °C 3.3: pH 6 - 7 4.1: ammonium formate / palladium 10% on activated carbon / ethanol / 30 - 70 °C View Scheme

tetrahydro-2,2-dimethyl-6-phenylmethyl-(3aS,4S,7R,7aS)-4,7-methano-4H-1,3-dioxolo[4,5-d][1,2]oxazine (155855-51-9) → [3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: palladium 10% on activated carbon; hydrogen / methanol / 14 h / 20 °C 2.1: N-ethyl-N,N-diisopropylamine / 4-methyl-2-pentanone / 2 h / 20 °C 3.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / -30 °C 3.2: 3 h / 20 °C 4.1: lithium borohydride / tetrahydrofuran / 5 h / 0 °C 5.1: 5%-palladium/activated carbon / methanol / 1 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: zinc; acetic acid / diethyl ether / 72.48 h / 0 - 25 °C 2.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 0 °C / Inert atmosphere 2.2: 4 h / 0 - 20 °C / Inert atmosphere 3.1: palladium 10% on activated carbon; hydrogen / methanol / 168 h / 40 °C / 7500.75 Torr View Scheme

(3aS,4S,6aR)-4-(iodomethyl)-6-methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxole (50600-40-3) → [3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9)

Conditions

Yield

Multi-step reaction with 8 steps 1.1: zinc / ethanol / 1 h / 70 °C 2.1: sodium carbonate / ethanol / 1 h / 50 °C 3.1: N,N-dimethyl-formamide; toluene / 5 h / 110 °C 4.1: palladium 10% on activated carbon; hydrogen / methanol / 14 h / 20 °C 5.1: N-ethyl-N,N-diisopropylamine / 4-methyl-2-pentanone / 2 h / 20 °C 6.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / -30 °C 6.2: 3 h / 20 °C 7.1: lithium borohydride / tetrahydrofuran / 5 h / 0 °C 8.1: 5%-palladium/activated carbon / methanol / 1 h / 20 °C View Scheme

(3aR,4S,6R,6aS)-6-(N,N-dibenzylamino)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-ol (1383715-55-6) → [3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium t-butanolate / N,N-dimethyl-formamide; tetrahydrofuran / 2 h / -10 - 5 °C 2.1: diisobutylaluminium hydride / toluene / 2.5 h / -25 - -20 °C 2.2: 0.25 h 3.1: hydrogen / 20% palladium hydroxide-activated charcoal / methanol / 10 h / 20 - 25 °C / 2327.23 Torr / Autoclave; Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1.1: potassium tert-butylate / dichloromethane; tetrahydrofuran / 5.5 h / 0 - 5 °C 2.1: hydrogen / palladium-on-charcoal / ethanol / 14 h / 43 - 48 °C / 3620.13 Torr / Autoclave 3.1: lithium borohydride / dichloromethane / 24 h / 20 - 25 °C / Inert atmosphere 3.2: 0.25 h 3.3: 0.5 h View Scheme
Multi-step reaction with 4 steps 1.1: potassium tert-butylate / dichloromethane; tetrahydrofuran / 5.5 h / 0 - 5 °C 2.1: palladium 10% on activated carbon; hydrogen / ethanol-d6 / 14 h / 43 - 48 °C / 3620.13 Torr / Inert atmosphere 2.2: -5 - 55 °C 3.1: potassium carbonate / water; dichloromethane / 20 - 25 °C / pH 10 - 10.5 4.1: lithium borohydride / dichloromethane / 24 h / 20 - 25 °C / pH 10 - 10.5 / Inert atmosphere View Scheme

tert-butyl [[(3aR,4S,6R,6aS)-6-(N,N-dibenzylamino)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]oxy]acetate (1383715-56-7) → [3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: diisobutylaluminium hydride / toluene / 2.5 h / -25 - -20 °C 1.2: 0.25 h 2.1: hydrogen / 20% palladium hydroxide-activated charcoal / methanol / 10 h / 20 - 25 °C / 2327.23 Torr / Autoclave; Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1.1: hydrogen / palladium-on-charcoal / ethanol / 14 h / 43 - 48 °C / 3620.13 Torr / Autoclave 2.1: lithium borohydride / dichloromethane / 24 h / 20 - 25 °C / Inert atmosphere 2.2: 0.25 h 2.3: 0.5 h View Scheme
Multi-step reaction with 3 steps 1.1: palladium 10% on activated carbon; hydrogen / ethanol-d6 / 14 h / 43 - 48 °C / 3620.13 Torr / Inert atmosphere 1.2: -5 - 55 °C 2.1: potassium carbonate / water; dichloromethane / 20 - 25 °C / pH 10 - 10.5 3.1: lithium borohydride / dichloromethane / 24 h / 20 - 25 °C / pH 10 - 10.5 / Inert atmosphere View Scheme

2-[[(3aR,4S,6R,6aS)-6-(N,N-dibenzylamino)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]oxy]ethanol (1383715-57-8) → [3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9)

Conditions	Yield
With hydrogen; 20% palladium hydroxide-activated charcoal In methanol at 20 - 25℃; under 2327.23 Torr; for 10h; Autoclave; Inert atmosphere;

(+/-)-1β-amino-2α,3α-O-isopropylidene-2α,3α,4β-cyclopentanetriol (88756-83-6) → [3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: ethanol / 20 °C / Reflux; Resolution of racemate 2: potassium carbonate / water; 4-methyl-2-pentanone 3: potassium tert-butylate 4: hydrogen / palladium on activated charcoal / ethanol View Scheme
Multi-step reaction with 4 steps 1: ethanol / 20 °C / Reflux; Resolution of racemate 2: potassium carbonate / water; 4-methyl-2-pentanone 3: potassium tert-butylate 4: hydrogen / palladium on activated charcoal / ethanol View Scheme

(3aR,4S,6R,6aS)-6-amino-2,2-dimethyltetrahydro-3aH-cyclopenta-[d][1,3]dioxol-4-ol D-(-)-mandelate (1392909-30-6) → [3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium carbonate / water; 4-methyl-2-pentanone 2: potassium tert-butylate 3: hydrogen / palladium on activated charcoal / ethanol View Scheme

(3aR,4S,6R,6aS)-6-amino-2,2-dimethyltetrahydro-3aH-cyclopenta-[d][1,3]dioxol-4-ol R-(-)-3-chloromandelate (1392909-34-0) → [3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium carbonate / water; 4-methyl-2-pentanone 2: potassium tert-butylate 3: hydrogen / palladium on activated charcoal / ethanol View Scheme

tert-butyl [[(3aR,4S,6R,6aS)-6-amino-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]oxy]acetate (1416158-39-8) → [3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9)

Conditions	Yield
Stage #1: tert-butyl [[(3aR,4S,6R,6aS)-6-amino-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]oxy]acetate With lithium borohydride In dichloromethane at 20 - 25℃; for 24h; Inert atmosphere; Stage #2: With acetic acid In dichloromethane for 0.25h; Stage #3: With potassium carbonate In dichloromethane for 0.5h;
With lithium borohydride In dichloromethane at 20 - 25℃; for 24h; pH=10 - 10.5; Inert atmosphere;	0.7 g

(3aS,4S,6aR)-4-(bromomethyl)-6-methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxole (78341-96-5) → [3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9)

Conditions

Yield

Multi-step reaction with 6 steps 1.1: hydrogenchloride; zinc/copper couple / water; methanol / 18 h / 25 °C 2.1: sodium carbonate / methanol / 0.5 h / 25 °C 3.1: toluene / 5 h / Reflux 4.1: zinc; acetic acid / diethyl ether / 72.48 h / 0 - 25 °C 5.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 0 °C / Inert atmosphere 5.2: 4 h / 0 - 20 °C / Inert atmosphere 6.1: palladium 10% on activated carbon; hydrogen / methanol / 168 h / 40 °C / 7500.75 Torr View Scheme

(3aR,4S,6R,6aS)-6-(benzylamino)-2,2-dimethyltetrahydro-3ah-cyclopenta-[d][1,3]-dioxol-4-ol (155855-53-1) → [3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 0 °C / Inert atmosphere 1.2: 4 h / 0 - 20 °C / Inert atmosphere 2.1: palladium 10% on activated carbon; hydrogen / methanol / 168 h / 40 °C / 7500.75 Torr View Scheme

D-ribose (10257-32-6) → [3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9)

Conditions	Yield
Multi-step reaction with 9 steps 1.1: hydrogenchloride / acetone / 22 h / 25 °C 2.1: pyridine / 4 h / -10 - -5 °C 3.1: lithium bromide / butanone / 22 h / 80 °C 4.1: hydrogenchloride; zinc/copper couple / water; methanol / 18 h / 25 °C 5.1: sodium carbonate / methanol / 0.5 h / 25 °C 6.1: toluene / 5 h / Reflux 7.1: zinc; acetic acid / diethyl ether / 72.48 h / 0 - 25 °C 8.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 0 °C / Inert atmosphere 8.2: 4 h / 0 - 20 °C / Inert atmosphere 9.1: palladium 10% on activated carbon; hydrogen / methanol / 168 h / 40 °C / 7500.75 Torr View Scheme
Multi-step reaction with 9 steps 1.1: Dowex WX8 / 72 h / 25 °C 2.1: pyridine / 4 h / -10 - -5 °C 3.1: lithium bromide / butanone / 22 h / 80 °C 4.1: hydrogenchloride; zinc/copper couple / water; methanol / 18 h / 25 °C 5.1: sodium carbonate / methanol / 0.5 h / 25 °C 6.1: toluene / 5 h / Reflux 7.1: zinc; acetic acid / diethyl ether / 72.48 h / 0 - 25 °C 8.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 0 °C / Inert atmosphere 8.2: 4 h / 0 - 20 °C / Inert atmosphere 9.1: palladium 10% on activated carbon; hydrogen / methanol / 168 h / 40 °C / 7500.75 Torr View Scheme

(3aS,4R,6S,6aR)-N-benzyl-6-(2-(benzyloxy)ethoxy)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-amine fumarate salt → [3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydrogencarbonate / water; ethyl acetate / 1 h / 20 °C 2: palladium 10% on activated carbon; hydrogen / methanol / 168 h / 40 °C / 7500.75 Torr View Scheme

tert-butyl [[(3aR,4S,6R,6aS)-6-amino-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]oxy]acetate L-(+)-tartaric acid salt (1416158-40-1) → [3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium carbonate / water; dichloromethane / 20 - 25 °C / pH 10 - 10.5 2: lithium borohydride / dichloromethane / 24 h / 20 - 25 °C / pH 10 - 10.5 / Inert atmosphere View Scheme

C15H19NO3 → [3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: ammonium formate; palladium 10% on activated carbon / methanol / 1.5 h / Reflux 2.1: potassium carbonate / water / 5.5 h / 20 °C 3.1: sodium hydride / N,N-dimethyl-formamide / 1 h / -20 °C 3.2: 6.33 h / -20 - 20 °C 4.1: sodium tetrahydroborate; ethanol / 4 h / 60 °C 5.1: ammonium formate; palladium 10% on activated carbon / ethanol / 1 h / 40 °C View Scheme
Multi-step reaction with 3 steps 1: zinc; acetic acid / tetrahydrofuran / 24 h / 5 - 25 °C 2: Nafion-H / toluene / 5 h / Reflux 3: palladium on activated charcoal; hydrogen / ethanol / 12 h / 50 - 60 °C / 750.08 Torr / Autoclave; Inert atmosphere View Scheme

4,6-dichloro-2-(propylsulfanyl)-5-pyrimidinamine (145783-15-9) + [3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9) → 2-[((3aR,4S,6R,6aS)-6-[[5-amino-6-chloro-2-(propylsulfanyl)-4-pyrimidinyl]amino]-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)oxy]-1-ethanol

Conditions	Yield
Stage #1: 4,6-dichloro-2-(propylsulfanyl)-5-pyrimidinamine; [3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol In water; N,N-dimethyl-formamide for 0.333333h; Stage #2: With triethylamine at 20℃; Reflux;	95%
With N-ethyl-N,N-diisopropylamine at 120 - 125℃; for 10h; Temperature; Inert atmosphere;	93.5%
With sodium hydrogencarbonate In water at 100℃; for 20h; Reagent/catalyst; Temperature;	88.3%

[3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9) + 4,6-dichloro-5-nitro-2-(propylsulfanyl)pyrimidine (145783-14-8) → 2-[((3aR,4S,6R,6aS)-6-{[5-nitro-6-chloro-2-(propylthio)-4-pyrimidinyl]amino}-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)oxy]-1-ethanol (1265919-25-2)

Conditions	Yield
With triethylamine In dichloromethane at 10 - 20℃; for 2h;	93.5%
In tetrahydrofuran at 0 - 10℃; for 2h;	45%

[3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9) → [3aR-(3aα, 4α,6α,6aα)]-[6-azido-2,2-dimethyl-tetrahydro-4H-cyclopenta-1,3-dioxane-4-oxy]ethanol

Conditions	Yield
With triflic azide; potassium carbonate; copper(II) sulfate In acetonitrile at 0 - 20℃; for 3h; Inert atmosphere;	92.6%

[3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9) + 2,4,6-trimethylbenzene-1-sulfonyl fluoride (384-98-5) → N-((3aS,4R,6S,6aR)-6-(2-hydroxyethoxy)-2,2-dimethyltetrahydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-2,4,6-trimethylbenzenesulfonamide

Conditions	Yield
With 1,1,3,3-Tetramethyldisiloxane; benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 25℃; for 24h; Sealed tube;	92%

[3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9) + 5-amino-2,4,6-trichloropyrimidine (91322-00-8) → 2-(((3aR,4S,6R,6aS)-6-((5-amino-2,6-dichloropyrimidin-4-yl)amino)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)oxy)ethanol

Conditions	Yield
With triethylamine at 110℃; Sealed tube;	83%

[3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9) → (1S,2S,3R,5S)-3-amino-5-(2-hydroxyethoxy)cyclopentane-1,2-diol (1444301-60-3)

Conditions	Yield
Stage #1: [3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol With hydrogenchloride In methanol; water at 20℃; for 24h; Stage #2: With sodium carbonate In isopropyl alcohol at 20℃; for 24h;	80%
With hydrogenchloride In methanol; water at 10℃; for 11h;	4.0 g

[3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9) + C7H9Cl2N3OS → C17H27ClN4O5S

Conditions	Yield
With triethylamine In pentan-1-ol at 115℃; for 10h;	78.75%

[3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9) + C7H9N5OS → C17H26N6O4S

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In tetrahydrofuran at 35℃; for 8h;	75.05%

[3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9) + 2,4,6-trichloro-5-nitropyrimidine (4359-87-9) → 2-(((3aR,4S,6R,6aS)-6-((2,6-dichloro-5-nitropyrimidin-4-yl)amino)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)oxy)ethanol

Conditions	Yield
With sodium carbonate In tetrahydrofuran at 20℃; for 4h;	59%

[3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9) + oxalic acid (144-62-7) → 2-[[(3aR,4S,6R,6aS)-6-amino-2,2-dimethyl-tetrahydro-3aH-cyclopenta[d][1,3]-dioxol-4-yl]oxy]-1-ethanol oxalate (1402150-30-4)

Conditions	Yield
In ethanol; water at 65℃;

[3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9) + O,O'-dibenzoyl-L-tartaric acid (2743-38-6) → bis[(3aS,4R,6S,6aR)-6-(2-hydroxyethoxy)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-aminium] 2,3-bis(benzoyloxy)succinate

Conditions	Yield
In ethanol at 10 - 50℃; for 4h;

[3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9) → 2-({(3aR,4S,6R,6aS)-6-[7-chloro-5-(propylthio)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-yl]-2,2-dimethyltetrahydro-3aH-cyclopentadiene[d][1,3]dioxolene-4-yl}oxy)ethanol

Conditions	Yield
Multi-step reaction with 2 steps 1: triethylamine; sodium iodide / 1,4-dioxane / 7 h / 120 °C 2: sodium nitrite / water; acetic acid; ethyl acetate / 30 °C View Scheme
Multi-step reaction with 2 steps 1: potassium tert-butylate 2: isopentyl nitrite / acetonitrile View Scheme
Multi-step reaction with 2 steps 1: sodium hydrogencarbonate / water / 20 h / 100 °C 2: sodium nitrite / water; acetic acid / 2 h / 0 °C View Scheme

[3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9) → ticagrelor (274693-27-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: triethylamine; sodium iodide / 1,4-dioxane / 7 h / 120 °C 2: sodium nitrite / water; acetic acid; ethyl acetate / 30 °C 3: N-ethyl-N,N-diisopropylamine / dichloromethane / 16 h 4: hydrogenchloride; water / methanol / 1 h View Scheme
Multi-step reaction with 4 steps 1.1: N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 2 h / 20 - 25 °C 2.1: sodium hydrogencarbonate; sodium dithionite / water; acetone / 2 h / 20 - 25 °C 3.1: sodium azide; acetic acid / toluene; water / 1 h / 5 - 10 °C 4.1: hydrogenchloride; water / toluene; methanol / 2 h / 25 - 30 °C 4.2: pH > 8 View Scheme
Multi-step reaction with 5 steps 1.1: N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 2 h / 20 - 25 °C 2.1: sodium hydrogencarbonate; sodium dithionite / water; acetone / 2 h / 20 - 25 °C 3.1: sodium azide; acetic acid / toluene; water / 1 h / 5 - 10 °C 4.1: potassium carbonate / acetone / 24 h / 25 - 60 °C 5.1: hydrogenchloride; water / methanol / 5.5 h / 20 - 55 °C 5.2: 25 - 30 °C / pH 10 View Scheme

[3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9) → C30H38F2N6O5S

Conditions	Yield
Multi-step reaction with 4 steps 1.1: triethylamine; sodium iodide / 1,4-dioxane / 7 h / 120 °C 2.1: sodium nitrite / water; acetic acid; ethyl acetate / 30 °C 3.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 16 h 4.1: triethylamine / acetonitrile / 0.5 h / 20 °C 4.2: 2 h / 20 °C View Scheme

[3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9) → C29H36F2N6O6S

Conditions	Yield
Multi-step reaction with 4 steps 1.1: triethylamine; sodium iodide / 1,4-dioxane / 7 h / 120 °C 2.1: sodium nitrite / water; acetic acid; ethyl acetate / 30 °C 3.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 16 h 4.1: triethylamine / acetonitrile / 0.5 h / 20 °C 4.2: 2 h / 20 °C View Scheme

[3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9) → C31H40F2N6O6S

Conditions	Yield
Multi-step reaction with 4 steps 1.1: triethylamine; sodium iodide / 1,4-dioxane / 7 h / 120 °C 2.1: sodium nitrite / water; acetic acid; ethyl acetate / 30 °C 3.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 16 h 4.1: triethylamine / acetonitrile / 0.5 h / 20 °C 4.2: 2 h / 20 °C View Scheme

[3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9) → 2-((1S,2S,3S,4R)-4-(7-(((1R,2S)-2-(3,4-difluorophenyl)cyclopropyl)amino-5-propylthio-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-2,3-dihydroxycyclopentyl)oxy) thyl carbonate (1381841-44-6)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: triethylamine; sodium iodide / 1,4-dioxane / 7 h / 120 °C 2.1: sodium nitrite / water; acetic acid; ethyl acetate / 30 °C 3.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 16 h 4.1: triethylamine / acetonitrile / 0.5 h / 20 °C 4.2: 2 h / 20 °C 5.1: iodine / methanol / 4 h / 60 °C View Scheme

[3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9) → 2-((1S,2S,3S,4R)-4-(7-(((1R,2S)-2-(3,4-difluorophenyl)cyclopropyl)amino-5-propylthio-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-2,3-dihydroxycyclopentyl)oxy)ethyl isobutyl carbonate (1381841-46-8)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: triethylamine; sodium iodide / 1,4-dioxane / 7 h / 120 °C 2.1: sodium nitrite / water; acetic acid; ethyl acetate / 30 °C 3.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 16 h 4.1: triethylamine / acetonitrile / 0.5 h / 20 °C 4.2: 2 h / 20 °C 5.1: iodine / methanol / 4 h / 60 °C View Scheme

[3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9) → [3aR-[3aα,4α,6α,(1R,2S),6aα]]-2-[6-[[[7-(2-(3,4-difluorophenyl)cyclopropyl)]amino-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]tetrahydro-2,2-dimethyl-4H-cyclopenteno-1,3-dioxolan-4-yl]oxy]ethanol (274693-26-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: triethylamine; sodium iodide / 1,4-dioxane / 7 h / 120 °C 2: sodium nitrite / water; acetic acid; ethyl acetate / 30 °C 3: N-ethyl-N,N-diisopropylamine / dichloromethane / 16 h View Scheme
Multi-step reaction with 4 steps 1: N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 2 h / 20 - 25 °C 2: sodium hydrogencarbonate; sodium dithionite / water; acetone / 2 h / 20 - 25 °C 3: sodium azide; acetic acid / toluene; water / 1 h / 5 - 10 °C 4: iodine / acetone / 2 h / 25 - 60 °C View Scheme
Multi-step reaction with 3 steps 1: potassium tert-butylate 2: isopentyl nitrite / acetonitrile 3: N-ethyl-N,N-diisopropylamine View Scheme

[3aR-(3aα,4α,6α,6aα)]-2-[[6-amino-2,2-dimethyl tetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (274693-55-9) → 2-((1S,2S,3S,4R)-4-(7-(((1R,2S)-2-(3,4-difluorophenyl)cyclopropyl)amino-5-propylthio-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-2,3-dihydroxycyclopentyl)oxy)ethyl butyrate (1381841-39-9)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: triethylamine; sodium iodide / 1,4-dioxane / 7 h / 120 °C 2.1: sodium nitrite / water; acetic acid; ethyl acetate / 30 °C 3.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 16 h 4.1: triethylamine / acetonitrile / 0.5 h / 20 °C 4.2: 2 h / 20 °C 5.1: iodine / methanol / 4 h / 60 °C View Scheme

Upstream product

• 324535-98-0 tert-butyl ((3aS,4R,6S,6aR)-6-hydroxy-2,2-dimethyltetrahydro-3aH-cyclopenta[d]-[1,3]dioxol-4-yl)carbamate 
• 59995-47-0 (S)-4-hydroxycyclopent-2-en-1-one 
• 542-92-7 cyclopenta-1,3-diene 
• 38838-06-1 methyl 5-deoxy-5-iodo-2,3-isopropylidene-β-D-ribofuranoside 
• 4137-56-8 methyl 2,3-O-isopropylidene-5-O-p-tolylsulfonyl-β-D-ribofuranoside 
• 4099-85-8 ((3aR,4R,6R,6aR)-6-methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol 
• 36468-53-8 β-D-ribofuranose 
• 1416158-40-1 tert-butyl [[(3aR,4S,6R,6aS)-6-amino-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]oxy]acetate L-(+)-tartaric acid salt 
• 10257-32-6 D-ribose 
• 155855-53-1 (3aR,4S,6R,6aS)-6-(benzylamino)-2,2-dimethyltetrahydro-3ah-cyclopenta-[d][1,3]-dioxol-4-ol 
• 78341-96-5 (3aS,4S,6aR)-4-(bromomethyl)-6-methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxole 
• 1444301-50-1 (3aS,4R,6S,6aR)-N-benzyl-6-(2-(benzyloxy)ethoxy)-2,2-dimethyl-tetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-amine 
• 1416158-39-8 tert-butyl [[(3aR,4S,6R,6aS)-6-amino-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]oxy]acetate 

Downstream Products

• 376608-74-1 2-[((3aR,4S,6R,6aS)-6-[[5-amino-6-chloro-2-(propylsulfanyl)-4-pyrimidinyl]amino]-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)oxy]-1-ethanol 
• 376608-75-2 2-({(3aR,4S,6R,6aS)-6-[7-chloro-5-(propylthio)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-yl]-2,2-dimethyltetrahydro-3aH-cyclopentadiene[d][1,3]dioxolene-4-yl}oxy)ethanol 
• 274693-27-5 ticagrelor 
• 1381841-44-6 2-((1S,2S,3S,4R)-4-(7-(((1R,2S)-2-(3,4-difluorophenyl)cyclopropyl)amino-5-propylthio-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-2,3-dihydroxycyclopentyl)oxy) thyl carbonate 
• 1381841-46-8 2-((1S,2S,3S,4R)-4-(7-(((1R,2S)-2-(3,4-difluorophenyl)cyclopropyl)amino-5-propylthio-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-2,3-dihydroxycyclopentyl)oxy)ethyl isobutyl carbonate 
• 274693-26-4 [3aR-[3aα,4α,6α,(1R,2S),6aα]]-2-[6-[[[7-(2-(3,4-difluorophenyl)cyclopropyl)]amino-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]tetrahydro-2,2-dimethyl-4H-cyclopenteno-1,3-dioxolan-4-yl]oxy]ethanol 
• 1381841-39-9 2-((1S,2S,3S,4R)-4-(7-(((1R,2S)-2-(3,4-difluorophenyl)cyclopropyl)amino-5-propylthio-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-2,3-dihydroxycyclopentyl)oxy)ethyl butyrate 
• 1383715-59-0 2-[[(3aR,4S,6R,6aS)-6-[[4-[N-[(1R,2S)-2-(3,4-difluorophenyl)cyclopropan-1-yl]-N-tert-butoxycarbonyl]amino]-2-(propylthio)-5-nitropyrimidin-6-yl]-2,2-dimethyl-tetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]oxy] ethanol 
• 376608-65-0 2-[[(3aR,4S,6R,6aS)-6-aminotetrahydro-2,2-dimethyl-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol (2R,3R)-2,3-dihydroxybutanedioic acid 
• 2096989-55-6 [1S-[1a,2a,3β(1S*,2R*),5B]]-3-[7-[2-(3,4-difluorophenyl)cyclopropylamino]-5-(propylthio)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-yl]-5-(2-hydroxyethoxy)cyclopentane-1,2-diol 

Relevant articles and documents

Preparation method of key intermediate A of ticagrelor

The invention discloses a preparation method of a key intermediate A of ticagrelor. The method comprises the following steps: (1) synthesis of an intermediate 9, (2) synthesis of an intermediate 10, and (3) synthesis of a key intermediate A. The synthesis of the intermediate 9 comprises the following steps: dropwise adding glacial acetic acid into a mixture of the intermediate 4, tetrahydrofuran and zinc powder at room temperature, stirring the mixture, keeping the temperature for 24 hours, neutralizing the reaction product with liquid caustic soda to neutrality, evaporating the solvent, and extracting, drying, filtering and concentrating the reaction product to obtain the intermediate 9. The invention discloses a preparation method of a key intermediate A of ticagrelor. On the basis of the existing preparation technology, through further improvement and optimization, the synthesis process is greatly shortened, the production cost is reduced, the safe and convenient preparation methodof the ticagrelor key intermediate A suitable for industrial large-scale production is provided, and the preparation method has good economic benefits and wide application prospects.

Production method of key intermediate of ticagrelor

The invention discloses a production method of a key intermediate compound I of ticagrelor. The production method comprises the following steps: (1) subjecting a compound II and di-tert-butyl dicarbonate to a reaction to obtain a compound III; (2) subjecting the compound III and 2-bromoacetate to a reaction, and conducting recrystallization to obtain a compound IV; (3) subjecting the compound IV to the action of a reducer to obtain a compound V; and (4) subjecting the compound V and a Boc removal reagent to obtain the compound I. Compared with the prior art, the production method of the key intermediate compound I of the ticagrelor has the advantages that the technology is simple, the purity of a finished product is high, the production cost is low, industrial production is easy, and the like.

Bio-synthesis method for ticagrelor intermediate and the intermediate therefrom

The invention discloses a bio-synthesis method for a ticagrelor intermediate and the intermediate therefrom. The method includes steps of: oxidizing a compound (2) to prepare a compound (3); performing an ortho-diol protection reaction to obtain a compound (4); performing an addition reaction to the compound (4) with ethylene oxide to obtain a compound (5); and performing bioconversion to the compound (5) to prepare the ticagrelor intermediate compound (1). Reaction equations in the method are represented in the specification. The synthesis method has advantages of creative technical route, simple operation, high synthesis yield and product purity, low cost and extensive source of raw materials and is suitable for industrial production. The ticagrelor intermediate can serve as an intermediate raw material for preparation of ticagrelor.

Method for preparing ticagrelor key intermediate

The invention relates to a chemical synthesis method of ticagrelor key intermediate 2-[[(3aR, 4S, 6R, 6aS)-6-aminotetrahydro-2,2-dimethyl-4H-cyclopenta-1,3-dioxolane-4-yl] oxy]ethanol (a key intermediate A). The method comprises the following steps: taking D-ribose as a raw material, and carrying out ten chemical reaction steps of 1-locus methylation and 2,3-loci isopropylidene protection, 4-locus derivatization, iodination, furan ring-opening, hydroxylamine reaction, palladium on carbon catalytic hydrogenation, amino Cbz protection, hydroxy protection, sodium borohydride reduction ester, Cbz removal protection and the like, thereby obtaining the key intermediate A. The raw materials are cheap and readily available, the preparation process is high in operability, steps of optical resolution, chiral induction and the like are avoided, the total yield is relatively high, and the product quality is better; particularly due to the use of sodium borohydride reduction ester, the preparation cost of ticagrelor is greatly reduced; and the method is suitable for large-scale industrial production.

Synthesis process of ticagrelor intermediate

The invention discloses a synthesis process of a ticagrelor intermediate. The synthesis process of the ticagrelor intermediate is characterized by including the steps: 1) under acidic condition, contacting benzaldoxime with cyclopentadiene for reaction so as to obtain a compound shown in formula I; 2) under the catalysis of osmium tetroxide, using hydrogen peroxide to oxidize the compound shown in the formula I so as to obtain a compound shown in formula II; 3) under the catalysis of p-toluenesulfonic acid, reacting the compound shown in the formula II and acetone to obtain a compound shown in formula III; 4) in the presence of an alkali, reacting the compound shown in the formula III with 2-bromoethyl alcohol so as to obtain a compound shown in formula IV; 5) reducing the compound shown in the formula IV so as to obtain the ticagrelor intermediate. The raw materials used here in the method provided herein are low in cost and easy to obtain, so that production cost; the use of chiral materials is not required, a high stereoselectivity product can be acquired through cycloaddition reaction, the steps are short, the reaction yield is very high, and a new approach for the synthesis of ticagrelor is provided.

Preparation method for ticagrelor intermediate

The invention discloses a preparation method for a ticagrelor intermediate. The preparation method comprises the following steps: 1) subjecting o-substituted benzaldoxime and cyclopentadiene to a contact reaction so as to obtain a compound as shown in a formula I; 2) oxidizing the compound as shown in the formula I with hydrogen peroxide under the catalysis of osmium tetroxide so as to obtain a compound as shown in a formula II; 3) reacting the compound as shown in the formula II with acetone under the catalysis of p-toluenesulfonic acid so as to obtain a compound as shown in a formula III; 4) reacting the compound as shown in the formula III with 2-bromoethanol in the presence of alkali so as to obtain a compound as shown in a formula IV; and 5) reducing the compound as shown in the formula IV so as to obtain the ticagrelor intermediate. The method provided by the invention uses cheap and easily available raw material, reduces production cost, and does not need any chiral raw material; a cycloaddition reaction enables a highly stereoselective product to be obtained; and the method is short in steps and high in reaction yield and provides a novel approach for synthesis of ticagrelor.

Process for Preparing Cyclopentylamine Derivatives and Intermediates Thereof

Disclosed herein is an improved process for the preparation of substituted cyclopentanamine derivatives, which are useful intermediates in the preparation of triazolo[4,5-d]pyrimidine compounds. Particularly described is an improved, commercially viable and industrially advantageous process for the preparation of a ticagrelor intermediate, [3aR-(3aα,4α,6α,6aα]-2-[[6-amino-2,2-dimethyltetrahydro-4H-cyclopenta-1,3-dioxol-4-yl]oxy]-ethanol, alternatively named, 2-[[(3aR,4S,6R,6aS)-6-amino-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]-dioxol-4-yl]oxy]-1-ethanol.

Synthesis of Aminocyclopentanetriol Derivatives

The present invention relates to the field of organic synthesis and describes the synthesis of specific intermediates suitable for the preparation of triazolopyrimidine compounds such as ticagrelor. The present invention provides in particular a process for the preparation of a compound of formula V comprising: a) providing a compound of formula IV , and b) reducing the compound of formula IV with activated zinc in the presence of copper to give the compound of formula V.

Synthesis and biological evaluation of ticagrelor derivatives as novel antiplatelet agents

Ticagrelor (1) is the first reversible P2Y12 receptor antagonist blocking adenine diphosphate (ADP)-induced platelet aggregation with rapid onset and offset of effects. In this study, synthesis of ticagrelor and its derivatives has been accomplished in a convergent way. The compound design was based on modifications of ticagrelor and its major metabolite (33) in order to ameliorate their pharmacokinetic properties and dosing profile. The final compounds (1a-g, 35a-g) were evaluated for their inhibitory effect on ADP-induced platelet aggregation in rats. The assay results showed that some compounds (e.g., 1b, 1d, 33, 35b, 35f) exhibited comparable potency with that of ticagrelor.

NEW INTERMEDIATES AND PROCESSES FOR PREPARING TICAGRELOR

The present invention is related to new intermediates and processes for preparing Ticagrelor disclosed in this patent application.