72821-79-5

Basic information

• Product Name: 6-(2-PROPENYL)-ERGOLINE-8-CARBOXYLIC ACID METHYL ESTER
• Synonyms: 6-(2-PROPENYL)-ERGOLINE-8-CARBOXYLIC ACID METHYL ESTER;Ergoline-8-carboxylic acid, 6-(2-propen-1-yl)-, Methyl ester, (8.beta.)-;6-Allyl-8β-carboxyergoline Methyl Ester;IACRGBGBDYCBKO-PUJMQQBBSA-N
• CAS NO: 72821-79-5
• Molecular Formula: C₁₉H₂₂N₂O₂
• Molecular Weight: 310.39
• Product Categories: API
• Mol File: 72821-79-5.mol
• Article Data: 6

Chemical Properties

• Boiling Point: 474.1°C at 760 mmHg
• Flash Point: 240.5°C
• Appearance: /
• Density: 1.19g/cm³
• Vapor Pressure: 3.73E-09mmHg at 25°C
• Refractive Index: 1.613
• PKA: 17.52±0.40(Predicted)
• CAS DataBase Reference: 6-(2-PROPENYL)-ERGOLINE-8-CARBOXYLIC ACID METHYL ESTER(CAS DataBase Reference)
• NIST Chemistry Reference: 6-(2-PROPENYL)-ERGOLINE-8-CARBOXYLIC ACID METHYL ESTER(72821-79-5)
• EPA Substance Registry System: 6-(2-PROPENYL)-ERGOLINE-8-CARBOXYLIC ACID METHYL ESTER(72821-79-5)

Safety Data

• HazardClass: IRRITANT
• Hazardous Substances Data: 72821-79-5(Hazardous Substances Data)

Usage

General Description

6-(2-propenyl)-ergoline-8-carboxylic acid methyl ester is a chemical compound that belongs to the ergoline class of compounds, which are known for their psychoactive and physiological effects. This particular compound is a methyl ester derivative of ergoline-8-carboxylic acid, which is a precursor to various compounds with biological activity. It is commonly used in research settings to study its effects on the central nervous system and to develop potential pharmaceutical agents for various medical applications. The compound is also known for its potential psychedelic and hallucinogenic effects, making it of interest to researchers in the field of psychopharmacology and neuropharmacology.

InChI:InChI=1/C19H22N2O2/c1-3-7-21-11-13(19(22)23-2)8-15-14-5-4-6-16-18(14)12(10-20-16)9-17(15)21/h3-6,10,13,15,17,20H,1,7-9,11H2,2H3/t13-,15-,17-/m1/s1

Synthetic route

methanol (67-56-1) + N-<<<3-(dimethylamino)propyl>amino>carbonyl>-N-ethyl-6-(2-propenyl)-ergoline-8β-carboxamide (81409-91-8) → methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (72821-79-5)

Conditions	Yield
With triethylamine at 20℃; Product distribution / selectivity;	96.5%

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) + allyl bromide (106-95-6) → methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (72821-79-5)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 35℃; for 2.5h;	94%
With potassium carbonate In N,N-dimethyl-formamide	80%

methyl ergoline-8β-carboxylate hydrochloride (1075250-77-9) + allyl bromide (106-95-6) → methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (72821-79-5)

Conditions	Yield
With triethylamine In N,N-dimethylformide at 20 - 30℃; for 4 - 5h; Product distribution / selectivity;

methanol (67-56-1) + cabergoline (81409-90-7) → methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (72821-79-5)

Conditions	Yield
With triethylamine

9,10-dihydrolysergic acid methyl ester (3006-19-7, 5143-94-2, 35470-53-2, 77842-02-5, 87247-99-2, 96648-31-6, 96648-32-7) → methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (72821-79-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: dmap / dichloromethane / 16 h / Reflux; Inert atmosphere 2: zinc / methanol; acetic acid / 1.08 h / 20 °C 3: potassium carbonate / N,N-dimethyl-formamide / 2.5 h / 35 °C View Scheme

9-methyl 7-(2,2,2-trichloroethyl) (6aR,9R,10aR)-6,6a,8,9,10,10a-hexahydroindolo[4,3-fg]quinoline-7,9(4H)-dicarboxylate (80993-64-2) → methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (72821-79-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: zinc / methanol; acetic acid / 1.08 h / 20 °C 2: potassium carbonate / N,N-dimethyl-formamide / 2.5 h / 35 °C View Scheme

Dihydroergocryptine (25447-66-9) → methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (72821-79-5)

Conditions	Yield
Multi-step reaction with 5 steps 1: sodium hydroxide; sodium dithionite / water / 4 h / Reflux 2: sulfuric acid / 15 h / 20 °C 3: dmap / dichloromethane / 16 h / Reflux; Inert atmosphere 4: zinc / methanol; acetic acid / 1.08 h / 20 °C 5: potassium carbonate / N,N-dimethyl-formamide / 2.5 h / 35 °C View Scheme

9,10-dihydrolysergic acid (5878-43-3) → methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (72821-79-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: sulfuric acid / 15 h / 20 °C 2: dmap / dichloromethane / 16 h / Reflux; Inert atmosphere 3: zinc / methanol; acetic acid / 1.08 h / 20 °C 4: potassium carbonate / N,N-dimethyl-formamide / 2.5 h / 35 °C View Scheme

methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (72821-79-5) → [(6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-yl]methanol (72821-88-6)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran; diethyl ether for 0.75h; Inert atmosphere; Cooling with ice;	87%
With sodium tetrahydroborate
With sodium borohydrid In 1,4-dioxane; methanol

methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (72821-79-5) + 1-amino-3-(dimethylamino)propane (109-55-7) → (6aR,9R,10aR)-7-allyl-N-[3-(dimethylamino)propyl]-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxamide (85329-86-8)

Conditions	Yield
In acetic acid Heating;	85%
With 2-hydroxypyridin In ethylene glycol at 100℃; for 18h;	85%
With acetic acid for 24h; Reflux;	74%

methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (72821-79-5) → (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylic acid (81409-74-7)

Conditions	Yield
Stage #1: methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate With sodium hydroxide; water In methanol at 20 - 30℃; for 2 - 3h; Stage #2: With hydrogenchloride In methanol; water at 0 - 5℃; for 1 - 2h; pH=6 - 6.5;	85%
With sodium hydroxide In methanol; water for 0.75h; Reflux;

methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (72821-79-5) → (6aR,9S,10aR)-7-Allyl-4,6,6a,7,8,9,10,10a-octahydro-indolo[4,3-fg]quinoline-9-carboxylic acid methyl ester (86891-16-9)

Conditions	Yield
With lithium diisopropyl amide In tetrahydrofuran at -20℃; for 0.333333h; Product distribution; other time;	70.7 % Chromat.

methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (72821-79-5) → 6-(2-propenyl)-ergoline-8β-carboxamide (85329-84-6)

Conditions	Yield
With ammonia; ammonium chloride In methanol at 120℃;	6.5 g

methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (72821-79-5) → cabergoline (81409-90-7)

Conditions	Yield
Multi-step reaction with 5 steps 1: 85 percent / 2-hydroxypyridine / ethane-1,2-diol / 18 h / 100 °C 2: 92 percent / 4-(dimethylamino)pyridine / tetrahydrofuran / 2 h / 40 °C 3: NaHMDS / tetrahydrofuran / -40 - 20 °C 4: propan-2-ol / 18 h / 50 °C 5: aqueous hydrochloric acid / H2O / 1 h / 80 °C View Scheme
Multi-step reaction with 2 steps 1: 85 percent / acetic acid / Heating 2: 81 percent / toluene / Heating View Scheme

methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (72821-79-5) → 7-allyl-9-ethylcarbamoyl-6a,7,8,9,10,10a-hexahydro-6H-indolo[4,3-fg]quinoline-4-carboxylic acid tert-butyl ester

Conditions	Yield
Multi-step reaction with 4 steps 1: 85 percent / 2-hydroxypyridine / ethane-1,2-diol / 18 h / 100 °C 2: 92 percent / 4-(dimethylamino)pyridine / tetrahydrofuran / 2 h / 40 °C 3: NaHMDS / tetrahydrofuran / -40 - 20 °C 4: propan-2-ol / 18 h / 50 °C View Scheme

methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (72821-79-5) → tert-butyl (5R,8R,10R)-6-allyl-8-[[[3-(dimethylamino)propyl]amino]carbonyl]ergoline-1-carboxylate (474397-67-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 85 percent / 2-hydroxypyridine / ethane-1,2-diol / 18 h / 100 °C 2: 92 percent / 4-(dimethylamino)pyridine / tetrahydrofuran / 2 h / 40 °C View Scheme

methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (72821-79-5) → tert-butyl (5R,8R,10R)-6-allyl-8-[[[3-(dimethylamino)propyl][(ethylamino)carbonyl]amino]carbonyl]ergoline-1-carboxylate (474397-69-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: 85 percent / 2-hydroxypyridine / ethane-1,2-diol / 18 h / 100 °C 2: 92 percent / 4-(dimethylamino)pyridine / tetrahydrofuran / 2 h / 40 °C 3: NaHMDS / tetrahydrofuran / -40 - 20 °C 4: propan-2-ol / 18 h / 50 °C View Scheme

methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (72821-79-5) → tert-butyl (5R,8R,10R)-6-allyl-8-[[[3-(dimethylamino)propyl](phenoxycarbonyl)amino]carbonyl]ergoline-1-carboxylate (474397-68-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: 85 percent / 2-hydroxypyridine / ethane-1,2-diol / 18 h / 100 °C 2: 92 percent / 4-(dimethylamino)pyridine / tetrahydrofuran / 2 h / 40 °C 3: NaHMDS / tetrahydrofuran / -40 - 20 °C View Scheme

methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (72821-79-5) → 3-((6aR,9S,10aR)-7-Allyl-4,6,6a,7,8,9,10,10a-octahydro-indolo[4,3-fg]quinolin-9-yl)-2-cyano-propionamide

Conditions	Yield
Multi-step reaction with 4 steps 1: NaBH4 4: NH3 View Scheme

methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (72821-79-5) → 3-((6aR,9S,10aR)-7-Allyl-4,6,6a,7,8,9,10,10a-octahydro-indolo[4,3-fg]quinolin-9-yl)-2-cyano-propionic acid ethyl ester (82842-08-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: NaBH4 View Scheme

methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (72821-79-5) → Toluene-4-sulfonic acid (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydro-indolo[4,3-fg]quinolin-9-ylmethyl ester (74627-24-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: NaBH4 View Scheme

methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (72821-79-5) → N-<(ethylamino)-carbonyl>-6-(2-propenyl)-ergoline-8β-carboxamide (85329-87-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 6.5 g / NH4Cl, NH3 / methanol / 120 °C 2: 90 percent View Scheme

methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (72821-79-5) → N-<3-(dimethylamino)propyl>-N-<(methylamino)-carbonyl>-6-(2-propenyl)-ergoline-8β-carboxamide (126554-48-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 85 percent / acetic acid / Heating 2: 80 percent View Scheme

methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (72821-79-5) → N-<3-(dimethylamino)propyl>-N-<(phenylamino)-carbonyl>-6-(2-propenyl)-ergoline-8β-carboxamide (126554-49-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 85 percent / acetic acid / Heating 2: 74 percent View Scheme

methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (72821-79-5) → (6aR,9R,10aR)-7-allyl-N9-[3-(dimethylamino)propyl]-N4-ethyl-N9-(ethylcarbamoyl)-6a,7,8,9,10,10a-hexahydroindolo[4,3-fg]quinoline-4,9(6H)-dicarboxamide (126554-50-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 85 percent / acetic acid / Heating 2: 0.57 g / toluene / Heating View Scheme

methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (72821-79-5) → (6aR,9R,10aR)-7-allyl-4-(ethylcarbamoyl)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinolone-9-carboxylic acid

Conditions	Yield
Multi-step reaction with 6 steps 1.1: lithium aluminium tetrahydride / tetrahydrofuran; diethyl ether / 0.75 h / Inert atmosphere; Cooling with ice 2.1: 1H-imidazole / N,N-dimethyl-formamide / 2 h / 20 °C 3.1: sodium hydride / tetrahydrofuran; mineral oil / 0.17 h / Inert atmosphere; Cooling with ice 3.2: 3 h / 20 °C / Inert atmosphere 4.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C 5.1: trifluoroacetic acid; dicyclohexyl-carbodiimide; pyridine; dimethyl sulfoxide / dichloromethane / 1.5 h / Inert atmosphere; Cooling with ice 6.1: 2-methyl-but-2-ene; sodium chlorite; sodium dihydrogenphosphate / water; tetrahydrofuran; tert-butyl alcohol / 1.5 h / Cooling with ice View Scheme
Multi-step reaction with 6 steps 1.1: lithium aluminium tetrahydride / tetrahydrofuran; diethyl ether / 0.75 h / Inert atmosphere; Cooling with ice 2.1: 1H-imidazole / N,N-dimethyl-formamide / 2 h / 20 °C 3.1: sodium hydride / tetrahydrofuran; mineral oil / 0.17 h / Inert atmosphere; Cooling with ice 3.2: 3 h / 20 °C / Inert atmosphere 4.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 45 h / 0 °C 5.1: trifluoroacetic acid; dicyclohexyl-carbodiimide; pyridine; dimethyl sulfoxide / dichloromethane / 1.5 h / Inert atmosphere; Cooling with ice 6.1: 2-methyl-but-2-ene; sodium chlorite; sodium dihydrogenphosphate / water; tetrahydrofuran; tert-butyl alcohol / 1.5 h / Cooling with ice View Scheme

methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (72821-79-5) → (6aR,9R,10aR)-7-allyl-9-[(tert-butyldimethylsilyl)oxy]methyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline

Conditions	Yield
Multi-step reaction with 2 steps 1: lithium aluminium tetrahydride / tetrahydrofuran; diethyl ether / 0.75 h / Inert atmosphere; Cooling with ice 2: 1H-imidazole / N,N-dimethyl-formamide / 2 h / 20 °C View Scheme

methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (72821-79-5) → (6aR,9R,10aR)-7-allyl-9-[(tert-butyldimethylsilyl)oxy]methyl-N-ethyl-6a,7,8,9,10,10a-hexahydroindolo[4,3-fg]quinoline-4(6H)-carboxamide

Conditions	Yield
Multi-step reaction with 3 steps 1.1: lithium aluminium tetrahydride / tetrahydrofuran; diethyl ether / 0.75 h / Inert atmosphere; Cooling with ice 2.1: 1H-imidazole / N,N-dimethyl-formamide / 2 h / 20 °C 3.1: sodium hydride / tetrahydrofuran; mineral oil / 0.17 h / Inert atmosphere; Cooling with ice 3.2: 3 h / 20 °C / Inert atmosphere View Scheme

methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (72821-79-5) → (6aR,9R,10aR)-7-allyl-N-ethyl-9-(hydroxymethyl)-6a,7,8,-9,10,10a-hexahydroindolo[4,3-fg]quinoline-4(6H)-carboxamide

Conditions	Yield
Multi-step reaction with 4 steps 1.1: lithium aluminium tetrahydride / tetrahydrofuran; diethyl ether / 0.75 h / Inert atmosphere; Cooling with ice 2.1: 1H-imidazole / N,N-dimethyl-formamide / 2 h / 20 °C 3.1: sodium hydride / tetrahydrofuran; mineral oil / 0.17 h / Inert atmosphere; Cooling with ice 3.2: 3 h / 20 °C / Inert atmosphere 4.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: lithium aluminium tetrahydride / tetrahydrofuran; diethyl ether / 0.75 h / Inert atmosphere; Cooling with ice 2.1: 1H-imidazole / N,N-dimethyl-formamide / 2 h / 20 °C 3.1: sodium hydride / tetrahydrofuran; mineral oil / 0.17 h / Inert atmosphere; Cooling with ice 3.2: 3 h / 20 °C / Inert atmosphere 4.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 45 h / 0 °C View Scheme

methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (72821-79-5) → (6aR,9R,10aR)-7-allyl-N-ethyl-9-formyl-6a,7,8,9,10,10a-hexahydroindolo[4,3-fg]quinoline-4(6H)-carboxamide

Conditions	Yield
Multi-step reaction with 5 steps 1.1: lithium aluminium tetrahydride / tetrahydrofuran; diethyl ether / 0.75 h / Inert atmosphere; Cooling with ice 2.1: 1H-imidazole / N,N-dimethyl-formamide / 2 h / 20 °C 3.1: sodium hydride / tetrahydrofuran; mineral oil / 0.17 h / Inert atmosphere; Cooling with ice 3.2: 3 h / 20 °C / Inert atmosphere 4.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C 5.1: trifluoroacetic acid; dicyclohexyl-carbodiimide; pyridine; dimethyl sulfoxide / dichloromethane / 1.5 h / Inert atmosphere; Cooling with ice View Scheme
Multi-step reaction with 5 steps 1.1: lithium aluminium tetrahydride / tetrahydrofuran; diethyl ether / 0.75 h / Inert atmosphere; Cooling with ice 2.1: 1H-imidazole / N,N-dimethyl-formamide / 2 h / 20 °C 3.1: sodium hydride / tetrahydrofuran; mineral oil / 0.17 h / Inert atmosphere; Cooling with ice 3.2: 3 h / 20 °C / Inert atmosphere 4.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 45 h / 0 °C 5.1: trifluoroacetic acid; dicyclohexyl-carbodiimide; pyridine; dimethyl sulfoxide / dichloromethane / 1.5 h / Inert atmosphere; Cooling with ice View Scheme

methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (72821-79-5) → (6aR,9R,10aR)-7-allyl-N9-[3-(dimethylamino)propyl]-N4-ethyl-6a,7,8,9,10,10a-hexahydroindolo[4,3-fg]quinoline-4,9(6H)-dicarboxamide

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 0.17 h / Inert atmosphere; Cooling with ice 1.2: 3 h / 20 °C / Inert atmosphere 2.1: sodium hydroxide / water; tetrahydrofuran / 1 h 3.1: 1,1'-carbonyldiimidazole / N,N-dimethyl-formamide / 3.5 h / 20 °C / Inert atmosphere 3.2: 20 h / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 7 steps 1.1: lithium aluminium tetrahydride / tetrahydrofuran; diethyl ether / 0.75 h / Inert atmosphere; Cooling with ice 2.1: 1H-imidazole / N,N-dimethyl-formamide / 2 h / 20 °C 3.1: sodium hydride / tetrahydrofuran; mineral oil / 0.17 h / Inert atmosphere; Cooling with ice 3.2: 3 h / 20 °C / Inert atmosphere 4.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C 5.1: trifluoroacetic acid; dicyclohexyl-carbodiimide; pyridine; dimethyl sulfoxide / dichloromethane / 1.5 h / Inert atmosphere; Cooling with ice 6.1: 2-methyl-but-2-ene; sodium chlorite; sodium dihydrogenphosphate / water; tetrahydrofuran; tert-butyl alcohol / 1.5 h / Cooling with ice 7.1: 1,1'-carbonyldiimidazole / N,N-dimethyl-formamide / 3.5 h / 20 °C / Inert atmosphere 7.2: 20 h / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 7 steps 1.1: lithium aluminium tetrahydride / tetrahydrofuran; diethyl ether / 0.75 h / Inert atmosphere; Cooling with ice 2.1: 1H-imidazole / N,N-dimethyl-formamide / 2 h / 20 °C 3.1: sodium hydride / tetrahydrofuran; mineral oil / 0.17 h / Inert atmosphere; Cooling with ice 3.2: 3 h / 20 °C / Inert atmosphere 4.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 45 h / 0 °C 5.1: trifluoroacetic acid; dicyclohexyl-carbodiimide; pyridine; dimethyl sulfoxide / dichloromethane / 1.5 h / Inert atmosphere; Cooling with ice 6.1: 2-methyl-but-2-ene; sodium chlorite; sodium dihydrogenphosphate / water; tetrahydrofuran; tert-butyl alcohol / 1.5 h / Cooling with ice 7.1: 1,1'-carbonyldiimidazole / N,N-dimethyl-formamide / 3.5 h / 20 °C / Inert atmosphere 7.2: 20 h / 20 °C / Inert atmosphere View Scheme

methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (72821-79-5) → (6aR,9R,10aR)-7-allyl-N9-[(3-(dimethylamino)propyl)carbamoyl]-N4,N9-diethyl-6a,7,8,9,10,10a-hexahydroindolo[4,3-fg]quinoline-4,9(6H)-dicarboxamide + (6aR,9R,10aR)-7-allyl-N9-[3-(dimethylamino)propyl]-N4-ethyl-N9-(ethylcarbamoyl)-6a,7,8,9,10,10a-hexahydroindolo[4,3-fg]quinoline-4,9(6H)-dicarboxamide (126554-50-5)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 0.17 h / Inert atmosphere; Cooling with ice 1.2: 3 h / 20 °C / Inert atmosphere 2.1: sodium hydroxide / water; tetrahydrofuran / 1 h 3.1: triethylamine / dichloromethane / 23 h / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 7 steps 1.1: lithium aluminium tetrahydride / tetrahydrofuran; diethyl ether / 0.75 h / Inert atmosphere; Cooling with ice 2.1: 1H-imidazole / N,N-dimethyl-formamide / 2 h / 20 °C 3.1: sodium hydride / tetrahydrofuran; mineral oil / 0.17 h / Inert atmosphere; Cooling with ice 3.2: 3 h / 20 °C / Inert atmosphere 4.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C 5.1: trifluoroacetic acid; dicyclohexyl-carbodiimide; pyridine; dimethyl sulfoxide / dichloromethane / 1.5 h / Inert atmosphere; Cooling with ice 6.1: 2-methyl-but-2-ene; sodium chlorite; sodium dihydrogenphosphate / water; tetrahydrofuran; tert-butyl alcohol / 1.5 h / Cooling with ice 7.1: triethylamine / dichloromethane / 23 h / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 7 steps 1.1: lithium aluminium tetrahydride / tetrahydrofuran; diethyl ether / 0.75 h / Inert atmosphere; Cooling with ice 2.1: 1H-imidazole / N,N-dimethyl-formamide / 2 h / 20 °C 3.1: sodium hydride / tetrahydrofuran; mineral oil / 0.17 h / Inert atmosphere; Cooling with ice 3.2: 3 h / 20 °C / Inert atmosphere 4.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 45 h / 0 °C 5.1: trifluoroacetic acid; dicyclohexyl-carbodiimide; pyridine; dimethyl sulfoxide / dichloromethane / 1.5 h / Inert atmosphere; Cooling with ice 6.1: 2-methyl-but-2-ene; sodium chlorite; sodium dihydrogenphosphate / water; tetrahydrofuran; tert-butyl alcohol / 1.5 h / Cooling with ice 7.1: triethylamine / dichloromethane / 23 h / 20 °C / Inert atmosphere View Scheme

Upstream product

• 5878-43-3 9,10-dihydrolysergic acid 
• 25447-66-9 Dihydroergocryptine 
• 80993-64-2 9-methyl 7-(2,2,2-trichloroethyl) (6aR,9R,10aR)-6,6a,8,9,10,10a-hexahydroindolo[4,3-fg]quinoline-7,9(4H)-dicarboxylate 
• 3006-19-7 9,10-dihydrolysergic acid methyl ester 
• 67-56-1 methanol 
• 81409-90-7 cabergoline 
• 81409-91-8 N-<<<3-(dimethylamino)propyl>amino>carbonyl>-N-ethyl-6-(2-propenyl)-ergoline-8β-carboxamide 
• 1075250-77-9 methyl ergoline-8β-carboxylate hydrochloride 
• 106-95-6 allyl bromide 
• 30341-92-5 methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate 

Downstream Products

• 81409-74-7 (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylic acid 
• 126554-50-5 (6aR,9R,10aR)-7-allyl-N⁹-[3-(dimethylamino)propyl]-N⁴-ethyl-N⁹-(ethylcarbamoyl)-6a,7,8,9,10,10a-hexahydroindolo[4,3-fg]quinoline-4,9(6H)-dicarboxamide 
• 126554-49-2 N-<3-(dimethylamino)propyl>-N-<(phenylamino)-carbonyl>-6-(2-propenyl)-ergoline-8β-carboxamide 
• 126554-48-1 N-<3-(dimethylamino)propyl>-N-<(methylamino)-carbonyl>-6-(2-propenyl)-ergoline-8β-carboxamide 
• 85329-87-9 N-<(ethylamino)-carbonyl>-6-(2-propenyl)-ergoline-8β-carboxamide 
• 474397-68-7 tert-butyl (5R,8R,10R)-6-allyl-8-[[[3-(dimethylamino)propyl](phenoxycarbonyl)amino]carbonyl]ergoline-1-carboxylate 
• 474397-69-8 tert-butyl (5R,8R,10R)-6-allyl-8-[[[3-(dimethylamino)propyl][(ethylamino)carbonyl]amino]carbonyl]ergoline-1-carboxylate 
• 474397-67-6 tert-butyl (5R,8R,10R)-6-allyl-8-[[[3-(dimethylamino)propyl]amino]carbonyl]ergoline-1-carboxylate 
• 81409-90-7 cabergoline 
• 85329-86-8 (6aR,9R,10aR)-7-allyl-N-[3-(dimethylamino)propyl]-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxamide 

Relevant articles and documents

Synthesis of European pharmacopoeial impurities A, B, C, and D of cabergoline

For the use of analytics, European pharmacopoeial impurities A, B, C, and D of cabergoline were synthesized. Ergocryptine was chosen as a starting material and synthesis was accomplished via two approaches, different in length and stereochemical outcome. A longer, indirect approach was realized through otherwise problematic oxidations of the 9,10-dihidrolysergol derivative, to the corresponding aldehyde and carboxylic acid. This was achieved by the use of activated DMSO and a Pinnick oxidation sequence. All four synthesized impurities are used as analytical standards in cabergoline manufacturing processes.

New and efficient process for the preperation of cabergoline and its intermediates

This invention relates to a new and efficient process for the production of dopamine agonists such as Cabergoline and the intermediates thereof.

Antihypertensive ergolinepropionamides

The synthesis and the antihypertensive activity in rats of a series of 6-methylergolin-8β-yl-propionic acid derivatives are reported. The prolactin lowering activity (nidation inhibition test) in rats and the acute toxicity in mice were also studied as a measure of the specificity and safety of the potential antihypertensive compounds. From the structure-activity considerations reported here it is clear how modifications at the C8 side chain can improve the selectivity of the antihypertensive effects, whilst introducing substituents in other positions of the ergoline skeleton afforded unfavourable results in this respect. Compound 5, namely 2(R,S)-cyano-3-(6-methylergolin-8β-yl)-propionamide, emerged as the most interesting antihypertensive derivative.