79098-75-2

Basic information

• Product Name: 3-(Piperidin-4-yl)-3,4-dihydroquinazolin-2(1H)-one
• Synonyms: 3-(Piperidin-4-yl)-3,4-dihydroquinazolin-2(1H)-one;3-(4-Piperidinyl)-3,4-dihydro-2(1H)-quinazolinone;3-(piperidin-4-yl)-1,2,3,4-tetrahydroquinazolin-2-one;3-Piperidin-4-yl-3,4-dihydro-1H-quinazolin-2-one;3,4-dihydro-3-(4-piperidinyl)-2(1H)-Quinazolinone;2(1H)-Quinazolinone, 3,4-dihydro-3-(4-piperidinyl)-;3,4-DIHYDRO-3-(4-PIPERIDINYL)-2(1H)-QUINAZOLINONE HCL;(1H)-quinazolinone, 3,4-dihydro-3-(4-piperidinyl)-
• CAS NO: 79098-75-2
• Molecular Formula: C₁₃H₁₇N₃O
• Molecular Weight: 231.29
• Mol File: 79098-75-2.mol
• Article Data: 7

Chemical Properties

• Boiling Point: 459.008 °C at 760 mmHg
• Flash Point: 231.4 °C
• Appearance: /
• Density: 1.18 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.581
• Storage Temp.: Keep in dark place,Inert atmosphere,Room temperature
• PKA: 14.85±0.20(Predicted)
• CAS DataBase Reference: 3-(Piperidin-4-yl)-3,4-dihydroquinazolin-2(1H)-one(CAS DataBase Reference)
• NIST Chemistry Reference: 3-(Piperidin-4-yl)-3,4-dihydroquinazolin-2(1H)-one(79098-75-2)
• EPA Substance Registry System: 3-(Piperidin-4-yl)-3,4-dihydroquinazolin-2(1H)-one(79098-75-2)

Safety Data

• HazardClass: IRRITANT
• Hazardous Substances Data: 79098-75-2(Hazardous Substances Data)

Usage

General Description

3-(Piperidin-4-yl)-3,4-dihydroquinazolin-2(1H)-one, also known as PD146176, is a chemical compound belonging to the class of quinazolinones. It is a synthetic organic compound that has been studied for its potential pharmacological properties, particularly as a histamine H3 receptor antagonist. 3-(Piperidin-4-yl)-3,4-dihydroquinazolin-2(1H)-one has been evaluated for its potential use in the treatment of cognitive disorders, such as Alzheimer's disease and schizophrenia, due to its ability to modulate neurotransmitter release and improve cognitive function. Research also suggests that PD146176 may have anti-inflammatory and neuroprotective effects, making it a promising candidate for further study and development as a potential therapeutic agent.

InChI:InChI=1/C13H17N3O/c17-13-15-12-4-2-1-3-10(12)9-16(13)11-5-7-14-8-6-11/h1-4,11,14H,5-9H2,(H,15,17)

Synthetic route

1-benzyl-4-(1,2,3,4-tetrahydro-2-oxo-3-quinazolinyl)piperidine (79098-88-7) → 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol for 48h;	100%
With hydrogen; Pd/C In ethanol at 60℃; under 1500.15 Torr;	85%
With hydrogen; palladium on activated charcoal In ethanol at 60℃; under 1500.15 Torr;	85%

tert-butyl 4-(2-oxo-1,2,3,4-tetrahydroquinazolin-3-yl)piperidine-1-carboxylate (960221-97-0) → 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2)

Conditions	Yield
With trifluoroacetic acid In dichloromethane at 20℃;	92%

2-nitro-benzaldehyde (552-89-6) → 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium tetrahydroborate; methanol 2: hydrogen / palladium on activated charcoal / ethanol 3: acetonitrile / Reflux View Scheme

4-amino-1-benzylpiperidine (50541-93-0) → 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium tetrahydroborate; methanol 2: hydrogen / palladium on activated charcoal / ethanol 3: acetonitrile / Reflux View Scheme
Multi-step reaction with 5 steps 1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol; triethylamine / N,N-dimethyl-formamide / 5 h / 70 °C 2: trifluoroacetic acid / dichloromethane / 20 h / 0 - 20 °C 3: lithium aluminium tetrahydride / 1,4-dioxane / 3 h / Reflux 4: tetrahydrofuran / 5 h / 20 °C 5: hydrogen; palladium 10% on activated carbon / methanol / 48 h View Scheme

2-amino-N-[1-(phenylmethyl)-4-piperidinyl]-benzenemethanamine (79099-03-9) + 1,1'-carbonyldiimidazole (530-62-1) → 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2)

Conditions	Yield
Stage #1: 2-amino-N-[1-(phenylmethyl)-4-piperidinyl]-benzenemethanamine; 1,1'-carbonyldiimidazole In acetonitrile Reflux; Stage #2: With hydrogen; palladium(II) hydroxide In methanol

(1-benzyl-piperidin-4-yl)-(2-nitro-benzyl)-amine (98754-28-0) → 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogen / palladium on activated charcoal / ethanol 2: acetonitrile / Reflux View Scheme

[2-(1-benzyl-piperidin-4-ylcarbamoyl)phenyl] tert-butyl carbamate → 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2)

Conditions	Yield
Multi-step reaction with 4 steps 1: trifluoroacetic acid / dichloromethane / 20 h / 0 - 20 °C 2: lithium aluminium tetrahydride / 1,4-dioxane / 3 h / Reflux 3: tetrahydrofuran / 5 h / 20 °C 4: hydrogen; palladium 10% on activated carbon / methanol / 48 h View Scheme

2-amino-N-(1-benzyl-piperidin-4-yl)-benzamide (83425-16-5) → 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: lithium aluminium tetrahydride / 1,4-dioxane / 3 h / Reflux 2: tetrahydrofuran / 5 h / 20 °C 3: hydrogen; palladium 10% on activated carbon / methanol / 48 h View Scheme

2-amino-N-[1-(phenylmethyl)-4-piperidinyl]-benzenemethanamine (79099-03-9) → 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: tetrahydrofuran / 5 h / 20 °C 2: hydrogen; palladium 10% on activated carbon / methanol / 48 h View Scheme

2-(tert-butyloxycarbonylamino)benzoic acid (68790-38-5) → 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2)

Conditions

Yield

Multi-step reaction with 5 steps 1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol; triethylamine / N,N-dimethyl-formamide / 5 h / 70 °C 2: trifluoroacetic acid / dichloromethane / 20 h / 0 - 20 °C 3: lithium aluminium tetrahydride / 1,4-dioxane / 3 h / Reflux 4: tetrahydrofuran / 5 h / 20 °C 5: hydrogen; palladium 10% on activated carbon / methanol / 48 h View Scheme

tert-butyl 4-((2-aminobenzyl)amino)piperidine-1-carboxylate (79098-98-9) → 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: triethylamine / acetonitrile / 18 h / 20 °C / Reflux 2: trifluoroacetic acid / dichloromethane / 20 °C View Scheme

N-tert-butyloxycarbonylpiperidin-4-one (79099-07-3) → 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium tris(acetoxy)borohydride / dichloromethane / 48 h / 20 °C 2: triethylamine / acetonitrile / 18 h / 20 °C / Reflux 3: trifluoroacetic acid / dichloromethane / 20 °C View Scheme

2-amino-1-benzylamine (4403-69-4) → 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium tris(acetoxy)borohydride / dichloromethane / 48 h / 20 °C 2: triethylamine / acetonitrile / 18 h / 20 °C / Reflux 3: trifluoroacetic acid / dichloromethane / 20 °C View Scheme

1,1'-Carbonyl-di-(1,2,4-triazole) (41864-22-6) + 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2) + 2-Amino-3-(3,5-dibromo-4-hydroxy-phenyl)-propionic acid methyl ester; hydrochloride (61039-29-0) → C24H26Br2N4O5

Conditions	Yield
With triethylamine In tetrahydrofuran	100%

1,1'-Carbonyl-di-(1,2,4-triazole) (41864-22-6) + 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2) + methyl 2-amino-3-(3-methoxyphenyl)propanoate hydrochloride → C25H30N4O5

Conditions	Yield
With triethylamine In tetrahydrofuran	100%

1,1'-Carbonyl-di-(1,2,4-triazole) (41864-22-6) + C8H12N2O2S*ClH + 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2) → C22H27N5O4S

Conditions	Yield
With triethylamine In tetrahydrofuran	100%

1,1'-Carbonyl-di-(1,2,4-triazole) (41864-22-6) + 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2) + 3-Nitro-phenylalanin-methylester-hydrochlorid → C24H27N5O6

Conditions	Yield
With triethylamine In tetrahydrofuran	100%

C13H13F3O4 + 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2) → C26H28F3N3O4

Conditions	Yield
With benzotriazol-1-ol; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In tetrahydrofuran	100%

3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2) + (+/-)-4-(3,4-dimethoxyphenyl)-3-methoxycarbonylbutanoic acid (78647-52-6) → C27H33N3O6

Conditions	Yield
With benzotriazol-1-ol; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In tetrahydrofuran	100%

β-(methoxycarbonyl)-1-naphthalenebutanoic acid (122872-06-4) + 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2) → C29H31N3O4

Conditions	Yield
With benzotriazol-1-ol; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In tetrahydrofuran	100%

3,5-dimethyl-4-hydroxy-β-(methoxycarbonyl)-benzenebutanoic acid + 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2) → C27H33N3O5

Conditions	Yield
With benzotriazol-1-ol; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In tetrahydrofuran	100%

1-(methoxycarbonyl)-2-(2-((2-(trimethylsilyl)ethoxy)methyl)-7-methyl-2H-indazol-5-yl)ethyl 4-nitrophenyl carbonate (855778-81-3) + 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2) → 1-(Methoxycarbonyl)-2-(2-((2-(trimethylsilyl)ethoxy)methyl)-7-methyl-2H-indazol-5-yl)ethyl 4-(1,2-dihydro-2-oxoquinazolin-3(4H)-yl)piperidine-1-carboxylate (865626-65-9)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In DMF (N,N-dimethyl-formamide) at 20℃; for 48h;	100%
With N-ethyl-N,N-diisopropylamine In DMF (N,N-dimethyl-formamide) at 20℃; for 48h;	100%

(R)-methyl 2-amino-3-(7-methyl-1H-indazol-5-yl)propanoate (890044-58-3) + 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2) → (R)-methyl-2-(4-(2-oxo-1,2-dihydroquinazolin-3(4H)-yl)piperidine-1-carboxamido)-3-(7-methyl-1H-indazol-5-yl)propanoate (890044-59-4)

Conditions	Yield
Stage #1: methyl (R)-2-amino-3-(7-methyl-1H-indazol-5-yl)propanoate With di(succinimido) carbonate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one In N,N-dimethyl-formamide for 24h;	100%

3,5-dibromo-4-hydroxy-β-(methoxycarbonyl)-benzenebutanoic acid (204695-24-9) + 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2) → C25H27Br2N3O5

Conditions	Yield
With benzotriazol-1-ol; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine In tetrahydrofuran; N,N-dimethyl-formamide	98%

3,5-dibromo-4-hydroxy-β-(methoxycarbonyl)-benzenebutanoic acid (204695-24-9) + 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2) → C25H27Br2N3O5

Conditions	Yield
With benzotriazol-1-ol; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In tetrahydrofuran	98%

3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2) → (S)-2-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-4-oxo-4-[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidin-1-yl]-butyric acid methyl ester (688020-82-8)

Conditions

Yield

Stage #1: (S)-2-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-succinic acid 1-methyl ester With benzotriazol-1-ol; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In DMF (N,N-dimethylformamide) at 20℃; for 1h; Stage #2: 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one In DMF (N,N-dimethylformamide) at 20℃; Stage #3: With potassium carbonate; citric acid more than 3 stages;

98%

3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2) → 3-(4-bromo-3-methyl-phenyl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidin-1-carbonyl]-amino}-propionic acid ethyl ester (688021-09-2)

Conditions	Yield
Stage #1: 2-amino-3-(4-bromo-3-methyl-phenyl)-propionic acid ethyl ester hydrochloride With 1,1'-Carbonyl-di-(1,2,4-triazole); triethylamine In DMF (N,N-dimethylformamide) at 0 - 20℃; for 2h; Stage #2: 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one In DMF (N,N-dimethylformamide) at 80℃; for 1.5h;	97%

1,1'-Carbonyl-di-(1,2,4-triazole) (41864-22-6) + 2-amino-3-(3,4-diethyl-phenyl)-propionic acid methylester (600725-39-1) + 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2) → 3-(3,4-diethyl-phenyl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidin-1-carbonyl]-amino}-propionic acid methylester (686297-92-7)

Conditions	Yield
Stage #1: 1,1'-Carbonyl-di-(1,2,4-triazole); 2-amino-3-(3,4-diethyl-phenyl)-propionic acid methylester With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 0 - 10℃; for 1.5h; Stage #2: In DMF (N,N-dimethyl-formamide) for 0.5h; Stage #3: 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one for 10h; Heating / reflux;	97%

(5-bromouracil)acetic acid (31385-63-4) + 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2) → 5-bromo-1-{2-oxo-2-[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidin-1-yl]-ethyl}-1H-pyrimidine-2,4-dione

Conditions	Yield
Stage #1: (5-bromouracil)acetic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 0.166667h; Stage #2: 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one In N,N-dimethyl-formamide at 20℃; for 18h;	97%

(+/-)-2-Amino-3-(7-chloro-1H-indazol-5-yl)-propionic acid methyl ester (635712-47-9) + 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2) + 1,1'-carbonyldiimidazole (530-62-1) → (+/-)-3-(7-chloro-1H-indazol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid methyl ester (635710-82-6)

Conditions	Yield
Stage #1: (+/-)-2-Amino-3-(7-chloro-1H-indazol-5-yl)-propionic acid methyl ester; 1,1'-carbonyldiimidazole In tetrahydrofuran at 0 - 20℃; for 0.25h; Stage #2: 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one In tetrahydrofuran at 20℃;	94%
In tetrahydrofuran

C17H20Br2O7 + 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2) → C30H35Br2N3O7

Conditions	Yield
With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine In tetrahydrofuran; N,N-dimethyl-formamide	93%

C16H16O4 + 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2) → C29H31N3O4

Conditions	Yield
With benzotriazol-1-ol; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In tetrahydrofuran	92%

(+/-)-2-Amino-3-(7-ethyl-1H-indazol-5-yl)-propionic acid methyl ester (635712-52-6) + 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2) + 1,1'-carbonyldiimidazole (530-62-1) → (+/-)-3-(7-ethyl-1H-indazol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid methyl ester (635710-84-8)

Conditions	Yield
Stage #1: (+/-)-2-Amino-3-(7-ethyl-1H-indazol-5-yl)-propionic acid methyl ester; 1,1'-carbonyldiimidazole In tetrahydrofuran at 0 - 20℃; for 0.333333h; Stage #2: 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one In tetrahydrofuran at 20℃;	92%
In tetrahydrofuran

1,1'-Carbonyl-di-(1,2,4-triazole) (41864-22-6) + C10H11Br2NO2*ClH + 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2) → C24H26Br2N4O4

Conditions	Yield
With triethylamine In tetrahydrofuran	90%

(R)-2-amino-3-[1-(2-trimethylsilanyl-ethanesulfonyl)-1H-indazol-5-yl]-propionic acid methyl ester (635713-85-8) + di(succinimido) carbonate (74124-79-1) + 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2) → (R)-2-{[4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-3-[1-(2-trimethylsilanyl-ethanesulfonyl)-1H-indazol-5-yl]-propionic acid methyl ester (635713-93-8)

Conditions	Yield
Stage #1: (R)-2-amino-3-[1-(2-trimethylsilanyl-ethanesulfonyl)-1H-indazol-5-yl]-propionic acid methyl ester; di(succinimido) carbonate With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 0.666667h; Stage #2: 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one In dichloromethane at 20℃;	90%
With N-ethyl-N,N-diisopropylamine In dichloromethane	1.15 g (90%)

3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2) → 2-(4-chloro-3-trifluoromethyl-benzyl)-4-oxo-4-[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidin-1-yl]-butanoic acid methyl ester (688021-42-3)

Conditions	Yield
Stage #1: 2-(4-chloro-3-trifluoromethyl-benzyl)-succinic acid 1-methyl ester With benzotriazol-1-ol; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In tetrahydrofuran; water at 20℃; for 0.166667h; Stage #2: 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one In tetrahydrofuran; water at 20℃; for 2h; Stage #3: With sodium hydrogencarbonate In water	89%

3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2) + 1,1'-carbonyldiimidazole (530-62-1) + 3,5-dibromo-D-tyrosine methyl ester → (R)-N-(1-oxo-(3,4-dihydroquinazolin-2(1H)-yl)piperidinyl)-3,5-dibromotyrosine methylester

Conditions	Yield
Stage #1: 1,1'-carbonyldiimidazole; 3,5-dibromo-D-tyrosine methyl ester With 1,2,4-Triazole In DMF (N,N-dimethyl-formamide) at 10 - 20℃; for 2h; Stage #2: 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one In DMF (N,N-dimethyl-formamide) at 50 - 55℃; for 1.5h;	88%
Stage #1: 1,1'-carbonyldiimidazole; 3,5-dibromo-D-tyrosine methyl ester With 1,2,4-Triazole In DMF (N,N-dimethyl-formamide) at 10 - 20℃; for 2h; Stage #2: 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one In DMF (N,N-dimethyl-formamide) at 20 - 55℃; for 1.5h; Product distribution / selectivity;	88%
With 1,2,4-Triazole In N,N-dimethyl-formamide	51%

C15H22N2O2 (936572-64-4) + di(succinimido) carbonate (74124-79-1) + 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2) → C29H37N5O4

Conditions	Yield
In dichloromethane	87%

4-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-3,3-bis-ethoxycarbonyl-butanoic acid (600725-56-2) + 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2) → 2-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-2-{2-oxo-2-[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidin-1-yl]-ethyl}-malonic acid diethyl ester (688020-58-8)

Conditions	Yield
With benzotriazol-1-ol; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine In tetrahydrofuran at 20℃; for 16h;	87%

3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2) + 6,7-dimethoxy-4-chloroquinazoline (13790-39-1) → 3-[1-(6,7-Dimethoxy-quinazolin-4-yl)-piperidin-4-yl]-3,4-dihydro-1H-quinazolin-2-one; hydrochloride (99161-60-1)

Conditions	Yield
In methanol Heating;	86%

(+/-)-2-amino-3-(7-ethyl-3 methyl-1H-indazol-5-yl)-propionic acid methyl ester (773887-24-4) + 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one (79098-75-2) → (+/-)-3-(7-ethyl-3-methyl-1H-indazol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid methyl ester (855776-60-2)

Conditions	Yield
Stage #1: (+/-)-2-amino-3-(7-ethyl-3 methyl-1H-indazol-5-yl)-propionic acid methyl ester; 1,1'-carbonyldiimidazole In tetrahydrofuran at 0 - 20℃; for 0.25h; Stage #2: 3-piperidin-4-yl-3,4-dihydro-1H-quinazoline-2-one In tetrahydrofuran at 20℃;	86%

Upstream product

• 79098-88-7 1-benzyl-4-(1,2,3,4-tetrahydro-2-oxo-3-quinazolinyl)piperidine 
• 552-89-6 2-nitro-benzaldehyde 
• 50541-93-0 4-amino-1-benzylpiperidine 
• 79099-03-9 2-amino-N-[1-(phenylmethyl)-4-piperidinyl]-benzenemethanamine 
• 530-62-1 1,1'-carbonyldiimidazole 
• 98754-28-0 (1-benzyl-piperidin-4-yl)-(2-nitro-benzyl)-amine 
• 83425-16-5 2-amino-N-(1-benzyl-piperidin-4-yl)-benzamide 
• 68790-38-5 2-(tert-butyloxycarbonylamino)benzoic acid 
• 960221-97-0 tert-butyl 4-(2-oxo-1,2,3,4-tetrahydroquinazolin-3-yl)piperidine-1-carboxylate 
• 79098-98-9 tert-butyl 4-((2-aminobenzyl)amino)piperidine-1-carboxylate 
• 79099-07-3 N-tert-butyloxycarbonylpiperidin-4-one 
• 4403-69-4 2-amino-1-benzylamine 

Downstream Products

• 205060-95-3 ethyl (R,S)-4-[4-(3,5-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-2-[[4-(1,1-dimethylethyl)phenyl]methyl]-2-(ethoxycarbonyl)-4-oxobutanoate 

Relevant articles and documents

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Olcegepant is one of the most potent and selective small molecule CGRP antagonists for the treatment of migraine headaches. Herein, we describe a new and efficient synthesis of the key piperidinyl dihydroquinazolinone (PDQ) fragment of olcegepant. PDQ plays a key role in the activity of CGRP antagonists. Primary improvements over existing methods include a high-yielding reductive amination step, greater overall yield, and operational simplicity. Coupling of PDQ to a D-tyrosine derivative effectively produced over one half of the total molecular structure of olcegepant. A unique tandem deprotection-nucleophilic addition sequence was also applied to the coupling of Fmoc-PDQ with phenyl isocyanate.

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METHOD FOR THE PRODUCTION OF 1-[N2-[3,5-DIBROMO-N-[[4-(3,4-DIHYDRO-2(1H)-OXOQUINAZOLINE-3-YL)-1-PIPERIDINYL]CARBONYL]-D-TYROSYL]-L-LYSYL]-4-(4-PYRIDINYL)-PIPERAZINE

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