30341-92-5

Basic information

• Product Name: ERGOLINE-8-CARBOXYLIC ACID METHYL ESTER
• Synonyms: ERGOLINE-8-CARBOXYLIC ACID METHYL ESTER;6-nor-9,10-dihydrolysergic acid methyl ester
• CAS NO: 30341-92-5
• Molecular Formula: C₁₆H₁₈N₂O₂
• Molecular Weight: 270.33
• Product Categories: API
• Mol File: 30341-92-5.mol
• Article Data: 5

Chemical Properties

• Boiling Point: 469.8°Cat760mmHg
• Flash Point: 237.9°C
• Appearance: /
• Density: 1.248g/cm³
• Vapor Pressure: 5.33E-09mmHg at 25°C
• Refractive Index: 1.628
• PKA: 17.40±0.40(Predicted)
• CAS DataBase Reference: ERGOLINE-8-CARBOXYLIC ACID METHYL ESTER(CAS DataBase Reference)
• NIST Chemistry Reference: ERGOLINE-8-CARBOXYLIC ACID METHYL ESTER(30341-92-5)
• EPA Substance Registry System: ERGOLINE-8-CARBOXYLIC ACID METHYL ESTER(30341-92-5)

Safety Data

• Hazardous Substances Data: 30341-92-5(Hazardous Substances Data)

Usage

General Description

ERGOLINE-8-CARBOXYLIC ACID METHYL ESTER is a chemical compound with potential medicinal and psychotropic properties. It is a methyl ester derivative of ergoline-8-carboxylic acid, which is a structure commonly found in ergoline alkaloids. ERGOLINE-8-CARBOXYLIC ACID METHYL ESTER has been studied for its potential use in the treatment of various medical conditions, including migraines and Parkinson's disease. It may also have psychoactive effects, making it of interest for research into its potential as a recreational drug or psychedelic substance. However, further research is needed to fully understand the effects and potential applications of this chemical.

InChI:InChI=1/C16H18N2O2/c1-20-16(19)10-5-12-11-3-2-4-13-15(11)9(7-17-13)6-14(12)18-8-10/h2-4,7,10,12,14,17-18H,5-6,8H2,1H3/t10-,12?,14-/m1/s1

Synthetic route

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)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5)

Conditions	Yield
With acetic acid; zinc for 60h; Heating;	72%
With zinc In methanol; acetic acid at 20℃; for 1.08333h;	71%

D-6-cyano-8β-methoxycarbonylergoline (51260-62-9) → methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5)

Conditions	Yield
With hydrogen; W-7 Raney Ni In N,N-dimethyl-formamide
aluminum nickel In N,N-dimethyl-formamide

9,10-dihydrolysergic acid (5878-43-3) → methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: H2SO4 2: CH2Cl2 3: H2 / W-7 Raney Ni / dimethylformamide View Scheme
Multi-step reaction with 3 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 View Scheme

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)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: CH2Cl2 2: H2 / W-7 Raney Ni / dimethylformamide View Scheme
Multi-step reaction with 2 steps 1: 90 percent / CH2Cl2 / 48 h / Heating 2: 72 percent / Zn, AcOH / 60 h / Heating View Scheme
Multi-step reaction with 2 steps 1: dmap / dichloromethane / 16 h / Reflux; Inert atmosphere 2: zinc / methanol; acetic acid / 1.08 h / 20 °C View Scheme

methanol (67-56-1) + ergoline-8-carboxylic acid → methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5)

Conditions	Yield
With sulfuric acid

Dihydroergocryptine (25447-66-9) → methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5)

Conditions	Yield
Multi-step reaction with 4 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 View Scheme

di-tert-butyl dicarbonate (24424-99-5) + methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → 1,6-di(tert-butoxycarbonyl)-ergoline-8β-carboxylic acid methyl ester

Conditions	Yield
With triethylamine; dmap In dichloromethane at 40℃; for 5h;	95.2%

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 (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) + phenyl isocyanate (103-71-9) → (4aR,8R,9aR)-methyl 6-(phenylcarbamoyl)-1,4,4a,6,7,8,9,9a-octahydroindolo[1,14-fg]quinoline-8-carboxylate (1624289-33-3)

Conditions	Yield
In dichloromethane at 20℃;	90%

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) + ethyl iodide (75-03-6) → 6-nor-6-n-ethyl-9,10-dihydrolysergic acid methyl ester (30341-94-7)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 50℃; for 24h;	75%
With potassium carbonate In N,N-dimethyl-formamide

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) + propyl bromide (106-94-5) → 6-nor-6-n-propyl-9,10-dihydrolysergic acid methyl ester (63719-09-5)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide	73%

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) + 1-iodo-propane (107-08-4) → 6-nor-6-n-propyl-9,10-dihydrolysergic acid methyl ester (63719-09-5)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 50℃; for 24h;	47%
With potassium carbonate In N,N-dimethyl-formamide
With potassium carbonate In methanol; chloroform; N,N-dimethyl-formamide

ethyl bromide (74-96-4) + methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → 6-nor-6-n-ethyl-9,10-dihydrolysergic acid methyl ester (30341-94-7)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide

Isobutyl iodide (513-38-2) + methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → (6aR,9R,10aR)-7-Isobutyl-4,6,6a,7,8,9,10,10a-octahydro-indolo[4,3-fg]quinoline-9-carboxylic acid methyl ester

pivaloyl chloride (3282-30-2) + methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → (6aR,9R,10aR)-7-(2,2-Dimethyl-propionyl)-4,6,6a,7,8,9,10,10a-octahydro-indolo[4,3-fg]quinoline-9-carboxylic acid methyl ester

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → (5R,8S,10R)-8-methoxycarbonylergoline (86891-09-0)

Conditions	Yield
With lithium diisopropyl amide In tetrahydrofuran at 0℃; for 2h; Product distribution; other time;	16.6 % Chromat.

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) + cyclopropanecarboxylic acid chloride (4023-34-1) → (6aR,9R,10aR)-7-Cyclopropanecarbonyl-4,6,6a,7,8,9,10,10a-octahydro-indolo[4,3-fg]quinoline-9-carboxylic acid methyl ester (82842-05-5)

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → (6-ethyl-ergolin-8-yl)-methanol (63719-20-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: K2CO3 / dimethylformamide 2: 94 percent / LiAlH4 / tetrahydrofuran / 0.5 h View Scheme

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → D-6-propyl-8β-hydroxymethylergoline (63719-21-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: K2CO3 / dimethylformamide 2: 96 percent / LiAlH4 / tetrahydrofuran / 0.5 h View Scheme

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → (6aR,9R,10aR)-9-Imidazol-1-ylmethyl-7-propyl-4,6,6a,7,8,9,10,10a-octahydro-indolo[4,3-fg]quinoline

Conditions	Yield
Multi-step reaction with 4 steps 1: K2CO3 / dimethylformamide 2: 96 percent / LiAlH4 / tetrahydrofuran / 0.5 h 3: 85 percent / pyridine / 3 h / Ambient temperature 4: 1.) NaH / 1.) DMF, 2.) DMF, 90 deg C, 2 h View Scheme

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → (5R,8R,10R)-6-propyl-8-(1,2,4-triazol-4-ylmethyl)ergoline

Conditions	Yield
Multi-step reaction with 4 steps 1: K2CO3 / dimethylformamide 2: 96 percent / LiAlH4 / tetrahydrofuran / 0.5 h 3: 85 percent / pyridine / 3 h / Ambient temperature 4: 1.) NaH / 1.) DMF, 2.) DMF, 80 deg C, 2 h View Scheme

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → Toluene-4-sulfonic acid (6aR,9R,10aR)-7-ethyl-4,6,6a,7,8,9,10,10a-octahydro-indolo[4,3-fg]quinolin-9-ylmethyl ester (74627-23-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: K2CO3 / dimethylformamide 2: 94 percent / LiAlH4 / tetrahydrofuran / 0.5 h 3: 81 percent / pyridine / 3 h / Ambient temperature View Scheme

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → Toluene-4-sulfonic acid (6aR,9R,10aR)-7-propyl-4,6,6a,7,8,9,10,10a-octahydro-indolo[4,3-fg]quinolin-9-ylmethyl ester (79675-18-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: K2CO3 / dimethylformamide 2: 96 percent / LiAlH4 / tetrahydrofuran / 0.5 h 3: 85 percent / pyridine / 3 h / Ambient temperature View Scheme

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → (6aR,9R,10aR)-7-Ethyl-9-[1,2,4]triazol-1-ylmethyl-4,6,6a,7,8,9,10,10a-octahydro-indolo[4,3-fg]quinoline

Conditions	Yield
Multi-step reaction with 4 steps 1: K2CO3 / dimethylformamide 2: 94 percent / LiAlH4 / tetrahydrofuran / 0.5 h 3: 81 percent / pyridine / 3 h / Ambient temperature 4: 1.) NaH / 1.) DMF, 2.) DMF, 90 deg C, 2 h View Scheme

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → (5R,8R,10R)-6-propyl-8-(1,2,4-triazol-1-ylmethyl)ergoline

Conditions	Yield
Multi-step reaction with 4 steps 1: K2CO3 / dimethylformamide 2: 96 percent / LiAlH4 / tetrahydrofuran / 0.5 h 3: 85 percent / pyridine / 3 h / Ambient temperature 4: 1.) NaH / 1.) DMF, 2.) DMF, 80 deg C, 2 h View Scheme

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → ((6aR,9R,10aR)-7-Isobutyl-4,6,6a,7,8,9,10,10a-octahydro-indolo[4,3-fg]quinolin-9-yl)-methanol

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

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → [(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
Multi-step reaction with 2 steps 2: NaBH4 View Scheme
Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 2.5 h / 35 °C 2: lithium aluminium tetrahydride / tetrahydrofuran; diethyl ether / 0.75 h / Inert atmosphere; Cooling with ice View Scheme

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → 6-cyclopropyl-methylergoline-8β-methanol (82842-03-3)

Conditions	Yield
Multi-step reaction with 2 steps 2: LiAlH4 View Scheme

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → 6-neopentylergoline-8β-methanol (88133-33-9)

Conditions	Yield
Multi-step reaction with 2 steps 2: LiAlH4 View Scheme

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → 2-Cyano-3-((6aR,9S,10aR)-7-isobutyl-4,6,6a,7,8,9,10,10a-octahydro-indolo[4,3-fg]quinolin-9-yl)-propionamide

Conditions	Yield
Multi-step reaction with 5 steps 2: NaBH4 5: NH3 View Scheme

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → 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 5 steps 2: NaBH4 5: NH3 View Scheme

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → 2-Cyano-3-[(6aR,9S,10aR)-7-(2,2-dimethyl-propyl)-4,6,6a,7,8,9,10,10a-octahydro-indolo[4,3-fg]quinolin-9-yl]-propionamide

Conditions	Yield
Multi-step reaction with 5 steps 2: LiAlH4 5: NH3 View Scheme

Upstream product

• 109698-20-6 4,5-dihydro-indolo[4,3-fg]quinoline-9-carboxylic acid ethyl ester 
• 109601-99-2 4-acetyl-4,5-dihydro-indolo[4,3-fg]quinoline-9-carbonitrile 
• 25447-66-9 Dihydroergocryptine 
• 67-56-1 methanol 
• 5878-43-3 9,10-dihydrolysergic acid 
• 51260-62-9 D-6-cyano-8β-methoxycarbonylergoline 
• 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 

Downstream Products

• 3006-19-7 rac-6-methyl-5α-ergoline-8β-carboxylic acid methyl ester 
• 3006-19-7 rac-6-methyl-5α-ergoline-8α-carboxylic acid methyl ester 
• 30341-94-7 rac-6-ethyl-ergoline-8β-carboxylic acid methyl ester 
• 63719-09-5 rac-6-propyl-ergoline-8β-carboxylic acid methyl ester 
• 2481-70-1 rac-9,10-dihydrolysergic acid 
• 3006-19-7 methyl (6aRS,9RS,10aSR)-7-methyl-4,6,6a,7,8,9,10,10a-octahydroindolo<4,3-fg>quinoline-9-carboxylate 
• 2481-70-1 rac-6-methyl-ergoline-8α-carboxylic acid 
• 3006-19-7 methyl (6aRS,9SS,10aSR)-7-methyl-4,6,6a,7,8,9,10,10a-octahydroindolo<4,3-fg>quinoline-9-carboxylate 
• 63719-09-5 6-nor-6-n-propyl-9,10-dihydrolysergic acid methyl ester 
• 81409-74-7 (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylic acid 
• 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 
• 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 
• 1624289-33-3 (4aR,8R,9aR)-methyl 6-(phenylcarbamoyl)-1,4,4a,6,7,8,9,9a-octahydroindolo[1,14-fg]quinoline-8-carboxylate 
• 1624289-51-5 ((6aR,9R,10aR)-4-(2-(dimethylamino)ethyl)-N-phenyl-9-(pyrrolidine-1-carbonyl)-6,6a,8,9,10,10a-hexahydroindolo[4,3-fg]quinoline-7(4H)carboxamide) 

Relevant articles and documents

Convenient synthesis of 6-nor-9,10-dihydrolysergic acid methyl ester

-

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.

Synthesis and structure-activity relationships of new (5R,8R,10R)-ergoline derivatives with antihypertensive or dopaminergic activity

A series of new (5R,8R,10R)-ergoline derivatives was synthesized, and their antihypertensive and dopaminergic activities were tested in conscious spontaneously hypertensive rats and in rats with unilateral 6- hydroxydopamine-induced lesions of the substantia nigra. (5R,8R,10R)-6- Alkyl-8-ergolinemethanols, prepared from the corresponding ergolinecarboxylates, were converted to the tosylates, which were treated with various five-membered heterocycles containing nitrogen atoms to afford the new ergolines. (5R,8R,10R)-8-(1,2,4-Triazol-1-ylmethyl)-6-methylergoline (4s, maleate: BAM-1110) exhibited potent dopaminergic activity, about 18- fold greater than that of bromocriptine mesylate. (5R,8R,10R)-8-(1,2,4- Triazol-1-ylmethyl)-6-propylergoline (8b, fumarate: BAM-1602) showed extremely potent dopaminergic activity, being about 220 and 1.15 times more active than bromocriptine mesylate and pergolide mesylate, respectively. Several compounds exhibited potent antihypertensive activity. Structure- activity relationships for antihypertensive and dopaminergic activities are discussed.