923289-21-8

Basic information

• Product Name: 4-Quinolinol, 7-methoxy-8-methyl-2-[4-(1-methylethyl)-2-thiazolyl]-
• Synonyms: 4-Quinolinol, 7-methoxy-8-methyl-2-[4-(1-methylethyl)-2-thiazolyl]-;2-(4-isopropylthiazol-2-yl)-7-methoxy-8-methylquinolin-4-ol;7-Methoxy-8-Methyl-2-[4-(1-Methylethyl)-2-thiazolyl]-;7-Methoxy-8-Methyl-2-[4-(1-Methylethyl)-2-thiazolyl]-4-Quinolinol;7-Methoxy-8-Methyl-2-[4-isopropylthiazol-2-yl]-4-hydroxy-quinoline;7-methoxy-8-methyl-2-(4-propan-2-yl-1,3-thiazol-2-yl)-1h-quinolin-4-one;2-(2-isopropylthiazol-4-yl)-7-methoxy-8-methylquinolin-4-ol;2-(4-Isopropylthiazol-2-yl)
• CAS NO: 923289-21-8
• Molecular Formula: C₁₇H₁₈N₂O₂S
• Molecular Weight: 314.4
• EINECS: 1308068-626-2
• Product Categories: Heterocycles
• Mol File: 923289-21-8.mol
• Article Data: 14

Chemical Properties

• Boiling Point: 518 ºC at 760 mmHg
• Flash Point: 267.1 ºC
• Appearance: /
• Density: 1.240
• Vapor Pressure: 2.37E-11mmHg at 25°C
• Refractive Index: 1.635
• Storage Temp.: 2-8°C
• PKA: 7.96±0.61(Predicted)
• CAS DataBase Reference: 4-Quinolinol, 7-methoxy-8-methyl-2-[4-(1-methylethyl)-2-thiazolyl]-(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Quinolinol, 7-methoxy-8-methyl-2-[4-(1-methylethyl)-2-thiazolyl]-(923289-21-8)
• EPA Substance Registry System: 4-Quinolinol, 7-methoxy-8-methyl-2-[4-(1-methylethyl)-2-thiazolyl]-(923289-21-8)

Safety Data

• Hazardous Substances Data: 923289-21-8(Hazardous Substances Data)

Usage

General Description

4-Quinolinol, 7-methoxy-8-methyl-2-[4-(1-methylethyl)-2-thiazolyl]- is a complex chemical compound that belongs to the group of organic compounds known as thiazolequinolines. Its molecular structure comprises a thiazole ring – an aromatic organic ring containing a sulfur atom and a nitrogen atom – fused with a methylated quinoline ring. Additionally, it has a methoxy group attached to the quinoline ring. 4-Quinolinol, 7-methoxy-8-methyl-2-[4-(1-methylethyl)-2-thiazolyl]- is generally used in the field of biochemistry and organic chemistry for various research purposes. However, details about its specific uses, prominent properties, toxicity, and safety measures are not well-documented, evidencing the need for further studies and exploration.

InChI:InChI=1/C17H18N2O2S/c1-9(2)13-8-22-17(19-13)12-7-14(20)11-5-6-15(21-4)10(3)16(11)18-12/h5-9H,1-4H3,(H,18,20)

Synthetic route

N-(6-acetyl-2-methyl-3-methoxyphenyl)-4-isopropylthiazole-2-carboxamide (923289-20-7) → 8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8)

Conditions	Yield
Stage #1: N-(6-acetyl-2-methyl-3-methoxyphenyl)-4-isopropylthiazole-2-carboxamide With potassium tert-butylate In tert-butyl alcohol for 18h; Reflux; Inert atmosphere; Stage #2: With hydrogenchloride In water; ethyl acetate at 20℃;	99%
With potassium tert-butylate In tert-butyl alcohol for 18h; Inert atmosphere; Reflux;	99%
With potassium tert-butylate In tert-butyl alcohol at 100℃; for 8h;	90%

2-(4,7-dimethoxy-8-methylquinoline-2-yl)-4-isopropylthiazole → 8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8)

Conditions	Yield
With hydrogenchloride In water for 14h; Inert atmosphere; Reflux;	80%

3-methyl-butan-2-one (563-80-4) → 8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: bromine / methanol / 3 h / -30 - 20 °C / Inert atmosphere 2.1: ethanol / 1.5 h / Inert atmosphere; Reflux 3.1: lithium hydroxide / tetrahydrofuran; methanol; water / 18 h / 20 °C / Inert atmosphere 4.1: HATU / N,N-dimethyl-formamide / 0.33 h / 20 °C / Inert atmosphere 4.2: Inert atmosphere 5.1: potassium tert-butylate / tert-butyl alcohol / 18 h / Inert atmosphere; Reflux View Scheme

1-(2-amino-4-methoxy-3-methyl-phenyl)ethanone (912347-94-5) → 8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: HATU / N,N-dimethyl-formamide / 0.33 h / 20 °C / Inert atmosphere 1.2: Inert atmosphere 2.1: potassium tert-butylate / tert-butyl alcohol / 18 h / Inert atmosphere; Reflux View Scheme

4-isopropylthiazole-2-carboxylic acid (1108658-73-6) → 8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: HATU / N,N-dimethyl-formamide / 0.33 h / 20 °C / Inert atmosphere 1.2: Inert atmosphere 2.1: potassium tert-butylate / tert-butyl alcohol / 18 h / Inert atmosphere; Reflux View Scheme
Multi-step reaction with 3 steps 1: oxalyl dichloride / dichloromethane / 4.5 h / 0 - 20 °C 2: acetone / 4.5 h / 0 - 20 °C 3: potassium tert-butylate / tert-butyl alcohol / 8 h / 100 °C View Scheme

C9H14BrNO2S → 8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: lithium hydroxide / tetrahydrofuran; methanol; water / 18 h / 20 °C / Inert atmosphere 2.1: HATU / N,N-dimethyl-formamide / 0.33 h / 20 °C / Inert atmosphere 2.2: Inert atmosphere 3.1: potassium tert-butylate / tert-butyl alcohol / 18 h / Inert atmosphere; Reflux View Scheme

1-bromo-3-methyl-2-butanone (19967-55-6) → 8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: ethanol / 1.5 h / Inert atmosphere; Reflux 2.1: lithium hydroxide / tetrahydrofuran; methanol; water / 18 h / 20 °C / Inert atmosphere 3.1: HATU / N,N-dimethyl-formamide / 0.33 h / 20 °C / Inert atmosphere 3.2: Inert atmosphere 4.1: potassium tert-butylate / tert-butyl alcohol / 18 h / Inert atmosphere; Reflux View Scheme
Multi-step reaction with 5 steps 1: ethanol / 2 h / 75 °C 2: lithium hydroxide monohydrate / methanol / 3.5 h / 0 - 20 °C 3: oxalyl dichloride / dichloromethane / 4.5 h / 0 - 20 °C 4: acetone / 4.5 h / 0 - 20 °C 5: potassium tert-butylate / tert-butyl alcohol / 8 h / 100 °C View Scheme

2-methyl-3-methoxyaniline (19500-02-8) → 8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: boron trichloride / dichloromethane; para-xylene / 0.5 h / 0 °C / Inert atmosphere 1.2: 0.5 h / 0 °C / Inert atmosphere 1.3: 19.75 h / 0 - 70 °C / Inert atmosphere 2.1: HATU / N,N-dimethyl-formamide / 0.33 h / 20 °C / Inert atmosphere 2.2: Inert atmosphere 3.1: potassium tert-butylate / tert-butyl alcohol / 18 h / Inert atmosphere; Reflux View Scheme
Multi-step reaction with 7 steps 1: methanol / 4 h / 20 °C 2: Eaton′s Reagent / 1 h / 50 °C 3: potassium carbonate / N,N-dimethyl-formamide / 5 h / 20 °C 4: ammonia / methanol / 20 °C 5: Lawessons reagent / tetrahydrofuran / 5 h / Inert atmosphere 6: methanol / 48 h / 20 °C 7: hydrogenchloride / water / 14 h / Inert atmosphere; Reflux View Scheme
Multi-step reaction with 7 steps 1: methanol / 4 h / 20 °C 2: Eaton′s Reagent / 1 h / 50 °C 3: potassium carbonate / N,N-dimethyl-formamide / 5 h / 20 °C 4: magnesium chloride / acetonitrile / 20 h / 80 °C 5: tetraphosphorus decasulfide; pyridine / 10 h / 110 °C / Inert atmosphere 6: manganese(IV) oxide / 24 h / Reflux 7: hydrogenchloride / water / 14 h / Inert atmosphere; Reflux View Scheme
Multi-step reaction with 8 steps 1: methanol / 4 h / 20 °C 2: Eaton′s Reagent / 1 h / 50 °C 3: potassium carbonate / N,N-dimethyl-formamide / 5 h / 20 °C 4: ammonia / methanol / 20 °C 5: Lawessons reagent / tetrahydrofuran / 5 h / Inert atmosphere 6: potassium carbonate / methanol / 24 h / 50 °C 7: isopropyl alcohol / 24 h / 100 °C 8: hydrogenchloride / water / 14 h / Inert atmosphere; Reflux View Scheme

N-(S)-(1-hydroxy-3-methylbutan-2-yl)-4,7-dimethoxy-8-methylquinoline-2-carboxamide → 8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: tetraphosphorus decasulfide; pyridine / 10 h / 110 °C / Inert atmosphere 2: manganese(IV) oxide / 24 h / Reflux 3: hydrogenchloride / water / 14 h / Inert atmosphere; Reflux View Scheme

2-(4,7-dimethoxy-8-methylquinoline-2-yl)-4-isopropyl-4,5-dihydrothiazole → 8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: manganese(IV) oxide / 24 h / Reflux 2: hydrogenchloride / water / 14 h / Inert atmosphere; Reflux View Scheme

4,7-dimethoxy-8-methylquinoline-2-carboxamide → 8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: Lawessons reagent / tetrahydrofuran / 5 h / Inert atmosphere 2: methanol / 48 h / 20 °C 3: hydrogenchloride / water / 14 h / Inert atmosphere; Reflux View Scheme
Multi-step reaction with 4 steps 1: Lawessons reagent / tetrahydrofuran / 5 h / Inert atmosphere 2: potassium carbonate / methanol / 24 h / 50 °C 3: isopropyl alcohol / 24 h / 100 °C 4: hydrogenchloride / water / 14 h / Inert atmosphere; Reflux View Scheme

4,7-dimethoxy-8-methylquinoline-2-carboxthioamide → 8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: methanol / 48 h / 20 °C 2: hydrogenchloride / water / 14 h / Inert atmosphere; Reflux View Scheme
Multi-step reaction with 3 steps 1: potassium carbonate / methanol / 24 h / 50 °C 2: isopropyl alcohol / 24 h / 100 °C 3: hydrogenchloride / water / 14 h / Inert atmosphere; Reflux View Scheme

dimethyl 2-(3-methoxy-2-methylphenylamino)-2-butenedioate (801281-88-9) → 8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8)

Conditions	Yield
Multi-step reaction with 6 steps 1: Eaton′s Reagent / 1 h / 50 °C 2: potassium carbonate / N,N-dimethyl-formamide / 5 h / 20 °C 3: ammonia / methanol / 20 °C 4: Lawessons reagent / tetrahydrofuran / 5 h / Inert atmosphere 5: methanol / 48 h / 20 °C 6: hydrogenchloride / water / 14 h / Inert atmosphere; Reflux View Scheme
Multi-step reaction with 6 steps 1: Eaton′s Reagent / 1 h / 50 °C 2: potassium carbonate / N,N-dimethyl-formamide / 5 h / 20 °C 3: magnesium chloride / acetonitrile / 20 h / 80 °C 4: tetraphosphorus decasulfide; pyridine / 10 h / 110 °C / Inert atmosphere 5: manganese(IV) oxide / 24 h / Reflux 6: hydrogenchloride / water / 14 h / Inert atmosphere; Reflux View Scheme
Multi-step reaction with 7 steps 1: Eaton′s Reagent / 1 h / 50 °C 2: potassium carbonate / N,N-dimethyl-formamide / 5 h / 20 °C 3: ammonia / methanol / 20 °C 4: Lawessons reagent / tetrahydrofuran / 5 h / Inert atmosphere 5: potassium carbonate / methanol / 24 h / 50 °C 6: isopropyl alcohol / 24 h / 100 °C 7: hydrogenchloride / water / 14 h / Inert atmosphere; Reflux View Scheme

4,5-dihydro-4-isopropyl-2-(4,7-dimethoxy-8-methylquinolin-2-yl)thiazol-4-ol → 8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: isopropyl alcohol / 24 h / 100 °C 2: hydrogenchloride / water / 14 h / Inert atmosphere; Reflux View Scheme

methyl 4-hydroxy-7-methoxy-8-methylquinoline-2-carboxylate (801281-89-0) → 8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8)

Conditions	Yield
Multi-step reaction with 5 steps 1: potassium carbonate / N,N-dimethyl-formamide / 5 h / 20 °C 2: ammonia / methanol / 20 °C 3: Lawessons reagent / tetrahydrofuran / 5 h / Inert atmosphere 4: methanol / 48 h / 20 °C 5: hydrogenchloride / water / 14 h / Inert atmosphere; Reflux View Scheme
Multi-step reaction with 5 steps 1: potassium carbonate / N,N-dimethyl-formamide / 5 h / 20 °C 2: magnesium chloride / acetonitrile / 20 h / 80 °C 3: tetraphosphorus decasulfide; pyridine / 10 h / 110 °C / Inert atmosphere 4: manganese(IV) oxide / 24 h / Reflux 5: hydrogenchloride / water / 14 h / Inert atmosphere; Reflux View Scheme
Multi-step reaction with 6 steps 1: potassium carbonate / N,N-dimethyl-formamide / 5 h / 20 °C 2: ammonia / methanol / 20 °C 3: Lawessons reagent / tetrahydrofuran / 5 h / Inert atmosphere 4: potassium carbonate / methanol / 24 h / 50 °C 5: isopropyl alcohol / 24 h / 100 °C 6: hydrogenchloride / water / 14 h / Inert atmosphere; Reflux View Scheme

methyl 4,7-dimethoxy-8-methylquinoline-2-carboxylate → 8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: ammonia / methanol / 20 °C 2: Lawessons reagent / tetrahydrofuran / 5 h / Inert atmosphere 3: methanol / 48 h / 20 °C 4: hydrogenchloride / water / 14 h / Inert atmosphere; Reflux View Scheme
Multi-step reaction with 4 steps 1: magnesium chloride / acetonitrile / 20 h / 80 °C 2: tetraphosphorus decasulfide; pyridine / 10 h / 110 °C / Inert atmosphere 3: manganese(IV) oxide / 24 h / Reflux 4: hydrogenchloride / water / 14 h / Inert atmosphere; Reflux View Scheme
Multi-step reaction with 5 steps 1: ammonia / methanol / 20 °C 2: Lawessons reagent / tetrahydrofuran / 5 h / Inert atmosphere 3: potassium carbonate / methanol / 24 h / 50 °C 4: isopropyl alcohol / 24 h / 100 °C 5: hydrogenchloride / water / 14 h / Inert atmosphere; Reflux View Scheme

4-(1-methylethyl)thiazole-2-carboxylic acid ethyl ester (156589-82-1) → 8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: lithium hydroxide monohydrate / methanol / 3.5 h / 0 - 20 °C 2: oxalyl dichloride / dichloromethane / 4.5 h / 0 - 20 °C 3: acetone / 4.5 h / 0 - 20 °C 4: potassium tert-butylate / tert-butyl alcohol / 8 h / 100 °C View Scheme

4-isopropylthiazole-2-carbonyl chloride (923289-59-2) → 8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: acetone / 4.5 h / 0 - 20 °C 2: potassium tert-butylate / tert-butyl alcohol / 8 h / 100 °C View Scheme

8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8) → 4-chloro-2-isopropylthiazolyl-7-methoxy-8-methylquinoline

Conditions	Yield
With NaOH In trichlorophosphate	96%
With sodium hydroxide; trichlorophosphate	4.11 g (91%)

8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8) + (2S,4S)-N-tert-butoxycarbonyl-4-hydroxyproline methyl ester (74844-91-0, 114676-69-6, 135042-17-0, 227935-38-8, 102195-79-9) → C28H35N3O6S (923604-80-2)

Conditions	Yield
With 2-(diphenylphosphino)pyridine; di-isopropyl azodicarboxylate In tetrahydrofuran at -15 - 20℃; for 17h;	85%
With 2-(diphenylphosphino)pyridine; di-tert-butyl-diazodicarboxylate In tetrahydrofuran at 20℃; for 24h; Inert atmosphere;	80%
With di-isopropyl azodicarboxylate In tetrahydrofuran at -15 - 20℃; Mitsunobu reaction;

8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8) + C32H44N4O11S → C43H57N5O8S

Conditions	Yield
With caesium carbonate In 1-methyl-pyrrolidin-2-one at 50℃;	80%

8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8) + C32H44N4O10S → C43H57N5O8S

Conditions	Yield
With caesium carbonate In 1-methyl-pyrrolidin-2-one at 50℃;	80%

8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8) + (1R,2R,4S)-1-benzyl 2-methyl 4-hydroxycyclopentane-1,2-dicarboxylate (1042695-89-5) → C32H34N2O6S (1042695-85-1)

Conditions	Yield
With di-isopropyl azodicarboxylate; triphenylphosphine In toluene at 0 - 20℃; for 2h; Product distribution / selectivity; Mitsunobu reaction;	75%
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 0 - 20℃; Product distribution / selectivity; Mitsunobu reaction;	71%

8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8) + C26H35BrN2O8S2 (1551161-65-9) → C37H48N4O7S2 (1551161-70-6)

Conditions	Yield
With caesium carbonate In 1-methyl-pyrrolidin-2-one at 75℃;	74%

8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8) + methyl-2-fluoro-1-((1R,2R,4S)-2-(hex-5-en-1-yl(methyl)carbamoyl)-4-hydroxycyclopentanecarboxamido)-cis-2-vinylcyclopropanecarboxylate → methyl 2-fluoro-1-((1R,2R,4R)-2-(hex-5-en-1-yl(methyl)carbamoyl)-4-((2-(4-isopropylthiazol-2-yl)-7-methoxy-8-methylquinolin-4-yl)oxy)cyclopentanecarboxamido)-cis-2-vinylcyclopropanecarboxylate

Conditions	Yield
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at -15℃; for 4h; Mitsunobu Displacement; Inert atmosphere;	72%

8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8) + methyl (1R,2R,4R)-2-[5-hexen-1-yl-(methyl)carbamoyl]-4-hydroxycyclopentanecarboxylate (1042695-84-0) → methyl (1R,2R,4S)-2-[5-hexen-1-yl(methyl)carbamoyl]-4-[[2-(4-isopropyl-1,3-thiazol-2-yl)-7-methoxy-8-methyl-4-quinolinyl]oxy]cyclopentanecarboxylate (1042695-87-3)

Conditions	Yield
With di-isopropyl azodicarboxylate; triphenylphosphine In toluene at 0 - 20℃; for 19 - 20h; Product distribution / selectivity;	71%

8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8) + ethyl(2S,6S,13aS,14aR,16aS)-6-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-2-hydroxy-5,16-dioxo-1,2,3,6,7,8,9,10,11,13a,14,15,16,16a-tetradecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a(5H)-carboxylate (744250-80-4) → (2R,6S,13aS,14aR,16aS)-6-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-2-{[8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinyl]oxy}-5,16-dioxo-1,2,3,6,7,8,9,10,11,13a,14,15,16,16a-tetradecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a(5H)carboxylic acid

Conditions

Yield

Stage #1: 8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol; ethyl(2S,6S,13aS,14aR,16aS)-6-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-2-hydroxy-5,16-dioxo-1,2,3,6,7,8,9,10,11,13a,14,15,16,16a-tetradecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a(5H)-carboxylate With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 0 - 20℃; Inert atmosphere; Stage #2: With water; lithium hydroxide In tetrahydrofuran; methanol at 20℃; for 18h; Stage #3: With hydrogenchloride In tetrahydrofuran; methanol

61%

8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8) + C21H32N2O8S (1218999-00-8) → C37H46N4O7S (1218999-01-9)

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 70℃;	58%

(1R,2S)-1-{[(1R,2R,4S)-2-(hex-5-enyl-methyl-carbamoyl)-4-hydroxy-cyclopentanecarbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid ethyl ester (922727-93-3) + 8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8) → ethyl (1R,2S)-2-ethenyl-1-({[(1R,2R,4R)-2-[hex-5-en-1-yl-(methyl)carbamoyl]-4-({7-methoxy-8-methyl-2-[4-(propan-2-yl)-1,3-thiazol-2-yl]quinolin-4-yl}oxy)cyclopentyl]carbonyl}-amino)cyclopropanecarboxylate (923604-56-2)

Conditions	Yield
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at -15℃; for 4.5h;	56%
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at -15℃; for 4.5h;	56%
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at -15 - 20℃; Mitsunobu reaction;

8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8) + C22H34N2O5 → C39H50N4O6S

Conditions	Yield
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at -15℃; for 4.5h;	56%

C25H32BrN3O9S2 (874124-85-3) + 8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8) → C36H45N5O8S2 (1285533-29-0)

Conditions	Yield
With caesium carbonate In 1-methyl-pyrrolidin-2-one at 75℃;	45%

8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8) + C19H28N2O8S (1218998-86-7) → C35H42N4O7S (1218998-87-8)

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 70℃; for 12h;	30%

8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8) + (1R,4R,6S,15R,18R)-18-(4-bromobenzenesulfonyloxy)-13-methyl-2,14-dioxo-3,13-diazatricyclo[13.4.0.0]nonadec-7-ene-4-carboxylic acid methyl ester → (1R,4R,6S,15R,18S)-18-[2-(4-isopropylthiazol-2-yl)-7-methoxy-8-methyl-quinolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diazatricyclo[13.4.0.0]nonadec-7-ene-4-carboxylic acid methyl ester

Conditions	Yield
Stage #1: 8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol; (1R,4R,6S,15R,18R)-18-(4-bromobenzenesulfonyloxy)-13-methyl-2,14-dioxo-3,13-diazatricyclo[13.4.0.0]nonadec-7-ene-4-carboxylic acid methyl ester at 70℃; for 40h; Stage #2: With potassium carbonate In 1-methyl-pyrrolidin-2-one at 85℃; for 4h;	27%

8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8) + C18H29N3O5 → (1R,4S,14S,Z)-ethyl 4-(2-(2-(4-isopropylthiazol-2-yl)-7-methoxy-8-methylquinolin-4-yloxy)ethyl)-7-methyl-3,6-dioxo-2,5,7-triazabicyclo[12.1.0]pentadec-12-ene-1-carboxylate (1108660-17-8)

Conditions	Yield
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 0 - 20℃; Mitsunobu reaction;	26%

8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8) + 18-hydroxy-14-(4-methoxy-benzyl)-2,15-dioxo-3,14,16-triaza-tricyclo-[14.3.0.0*4,6*]nonadec-7-ene-4-carboxyric acid ethyl ester (923274-86-6) → C44H53N5O7S

Conditions	Yield
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 0 - 20℃; Product distribution / selectivity;

8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8) + C21H32N2O5 (1079097-27-0) → C38H48N4O6S (1079097-45-2)

Conditions	Yield
With di-isopropyl azodicarboxylate; triphenylphosphine at -20 - 20℃; Mitsunobu reaction;

8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8) + C22H34N2O5 (923289-03-6) → C39H50N4O6S (1079097-40-7)

Conditions	Yield
With di-isopropyl azodicarboxylate; triphenylphosphine at -20 - 20℃; Mitsunobu reaction;

8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8) + C25H31BrN2O8S → C37H46N4O7S (1218998-94-7)

Conditions	Yield
With caesium carbonate In 1-methyl-pyrrolidin-2-one at 50℃; for 15h; Sealed tube;

8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8) → (2R,6S,13aS,14aR,16aS)-N-(cyclopropylsulfonyl)-2-{[8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinyl]oxy}-5,16-dioxo-6-[(1-pyrrolidinylcarbonyl)amino]-1,2,3,6,7,8,9,10,11,13a,14,15,16,16a-tetradecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a(5H)-carboxamide

Conditions

Yield

Multi-step reaction with 5 steps 1.1: di-isopropyl azodicarboxylate; triphenylphosphine / tetrahydrofuran; toluene / 18 h / 0 - 20 °C / Inert atmosphere 2.1: lithium hydroxide / tetrahydrofuran; methanol; water / 18 h / 20 °C / Inert atmosphere 3.1: 1,1'-carbonyldiimidazole / N,N-dimethyl-formamide / 1 h / 40 °C / Inert atmosphere 3.2: 18 h / 40 °C / Inert atmosphere 4.1: hydrogenchloride / 1,4-dioxane; water; ethyl acetate; N,N-dimethyl-formamide / 3 h / Inert atmosphere 5.1: N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 0 - 20 °C / Inert atmosphere 5.2: Inert atmosphere View Scheme

8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8) → C45H59N7O8S2

Conditions

Yield

Multi-step reaction with 5 steps 1.1: di-isopropyl azodicarboxylate; triphenylphosphine / tetrahydrofuran; toluene / 18 h / 0 - 20 °C / Inert atmosphere 2.1: lithium hydroxide / tetrahydrofuran; methanol; water / 18 h / 20 °C / Inert atmosphere 3.1: 1,1'-carbonyldiimidazole / N,N-dimethyl-formamide / 1 h / 40 °C / Inert atmosphere 3.2: 18 h / 40 °C / Inert atmosphere 4.1: hydrogenchloride / 1,4-dioxane; water; ethyl acetate; N,N-dimethyl-formamide / 3 h / Inert atmosphere 5.1: N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 0 - 20 °C / Inert atmosphere 5.2: Inert atmosphere View Scheme

8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8) → (2R,6S,13aS,14aR,16aS)-N-(cyclopropylsulfonyl)-2-{[8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinyl]oxy}-5,16-dioxo-6-[(1-piperidinylcarbonyl)amino]-1,2,3,6,7,8,9,10,11,13a,14,15,16,16a-tetradecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a(5H)-carboxamide

Conditions

Yield

Multi-step reaction with 5 steps 1.1: di-isopropyl azodicarboxylate; triphenylphosphine / tetrahydrofuran; toluene / 18 h / 0 - 20 °C / Inert atmosphere 2.1: lithium hydroxide / tetrahydrofuran; methanol; water / 18 h / 20 °C / Inert atmosphere 3.1: 1,1'-carbonyldiimidazole / N,N-dimethyl-formamide / 1 h / 40 °C / Inert atmosphere 3.2: 18 h / 40 °C / Inert atmosphere 4.1: hydrogenchloride / 1,4-dioxane; water; ethyl acetate; N,N-dimethyl-formamide / 3 h / Inert atmosphere 5.1: N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 0 - 20 °C / Inert atmosphere 5.2: Inert atmosphere View Scheme

8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8) → (2R,6S,13aS,14aR,16aS)-N-(cyclopropylsulfonyl)-6-{[(4-hydroxy-1-piperidinyl)carbonyl]amino}-2-{[8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinyl]oxy}-5,16-dioxo-1,2,3,6,7,8,9,10,11,13a,14,15,16 ,16a-tetradecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a(5H)-carboxamide

Conditions

Yield

Multi-step reaction with 5 steps 1.1: di-isopropyl azodicarboxylate; triphenylphosphine / tetrahydrofuran; toluene / 18 h / 0 - 20 °C / Inert atmosphere 2.1: lithium hydroxide / tetrahydrofuran; methanol; water / 18 h / 20 °C / Inert atmosphere 3.1: 1,1'-carbonyldiimidazole / N,N-dimethyl-formamide / 1 h / 40 °C / Inert atmosphere 3.2: 18 h / 40 °C / Inert atmosphere 4.1: hydrogenchloride / 1,4-dioxane; water; ethyl acetate; N,N-dimethyl-formamide / 3 h / Inert atmosphere 5.1: N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 0 - 20 °C / Inert atmosphere 5.2: Inert atmosphere View Scheme

8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol (923289-21-8) → (2R,6S,13aS,14aR,16aS)-N-(cyclopropylsulfonyl)-6-({[4-(hydroxymethyl)-1-piperidinyl]carbonyl}amino)-2-{[8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinyl]oxy}-5,16-dioxo-1,2,3,6,7,8,9,10,11,13a,14,15,16,16a-tetradecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a(5H)-carboxamide

Conditions

Yield

Multi-step reaction with 5 steps 1.1: di-isopropyl azodicarboxylate; triphenylphosphine / tetrahydrofuran; toluene / 18 h / 0 - 20 °C / Inert atmosphere 2.1: lithium hydroxide / tetrahydrofuran; methanol; water / 18 h / 20 °C / Inert atmosphere 3.1: 1,1'-carbonyldiimidazole / N,N-dimethyl-formamide / 1 h / 40 °C / Inert atmosphere 3.2: 18 h / 40 °C / Inert atmosphere 4.1: hydrogenchloride / 1,4-dioxane; water; ethyl acetate; N,N-dimethyl-formamide / 3 h / Inert atmosphere 5.1: N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 0 - 20 °C / Inert atmosphere 5.2: Inert atmosphere View Scheme

Upstream product

• 923289-20-7 N-(6-acetyl-2-methyl-3-methoxyphenyl)-4-isopropylthiazole-2-carboxamide 
• 563-80-4 3-methyl-butan-2-one 
• 912347-94-5 1-(2-amino-4-methoxy-3-methyl-phenyl)ethanone 
• 1108658-73-6 4-isopropylthiazole-2-carboxylic acid 
• 19967-55-6 1-bromo-3-methyl-2-butanone 
• 19500-02-8 2-methyl-3-methoxyaniline 
• 801281-88-9 dimethyl 2-(3-methoxy-2-methylphenylamino)-2-butenedioate 
• 801281-89-0 methyl 4-hydroxy-7-methoxy-8-methylquinoline-2-carboxylate 
• 156589-82-1 4-(1-methylethyl)thiazole-2-carboxylic acid ethyl ester 
• 923289-59-2 4-isopropylthiazole-2-carbonyl chloride 

Downstream Products

• 923604-56-2 ethyl (1R,2S)-2-ethenyl-1-({[(1R,2R,4R)-2-[hex-5-en-1-yl-(methyl)carbamoyl]-4-({7-methoxy-8-methyl-2-[4-(propan-2-yl)-1,3-thiazol-2-yl]quinolin-4-yl}oxy)cyclopentyl]carbonyl}-amino)cyclopropanecarboxylate 
• 1042695-85-1 C₃₂H₃₄N₂O₆S 
• 1042695-87-3 methyl (1R,2R,4S)-2-[5-hexen-1-yl(methyl)carbamoyl]-4-[[2-(4-isopropyl-1,3-thiazol-2-yl)-7-methoxy-8-methyl-4-quinolinyl]oxy]cyclopentanecarboxylate 
• 1042695-88-4 C₃₁H₃₉N₃O₅S 

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