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[ CAS No. 798563-50-5 ] {[proInfo.proName]}

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3d Animation Molecule Structure of 798563-50-5
Chemical Structure| 798563-50-5
Chemical Structure| 798563-50-5
Structure of 798563-50-5 * Storage: {[proInfo.prStorage]}
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Product Details of [ 798563-50-5 ]

CAS No. :798563-50-5 MDL No. :MFCD13185602
Formula : C9H9FO3 Boiling Point : -
Linear Structure Formula :- InChI Key :FQQPGAGVFVTCDB-UHFFFAOYSA-N
M.W : 184.16 Pubchem ID :21034868
Synonyms :

Calculated chemistry of [ 798563-50-5 ]

Physicochemical Properties

Num. heavy atoms : 13
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.22
Num. rotatable bonds : 3
Num. H-bond acceptors : 4.0
Num. H-bond donors : 1.0
Molar Refractivity : 44.44
TPSA : 46.53 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.39 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.62
Log Po/w (XLOGP3) : 1.46
Log Po/w (WLOGP) : 1.88
Log Po/w (MLOGP) : 1.79
Log Po/w (SILICOS-IT) : 1.98
Consensus Log Po/w : 1.75

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.56

Water Solubility

Log S (ESOL) : -2.05
Solubility : 1.66 mg/ml ; 0.00901 mol/l
Class : Soluble
Log S (Ali) : -2.04
Solubility : 1.67 mg/ml ; 0.00905 mol/l
Class : Soluble
Log S (SILICOS-IT) : -2.58
Solubility : 0.481 mg/ml ; 0.00261 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.68

Safety of [ 798563-50-5 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 798563-50-5 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 798563-50-5 ]

[ 798563-50-5 ] Synthesis Path-Downstream   1~50

  • 1
  • [ 798563-50-5 ]
  • α-aminomethyl-(3,4-dimethoxy)benzene acetic acid ethyl ester hydrochloride [ No CAS ]
  • [ 1344688-70-5 ]
YieldReaction ConditionsOperation in experiment
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; for 12h; 26 Example 26; 1- (2-FLUORO-5-METHOXY-BENZOYL)-6, 7-DIMETHOXY-ISOQUINOLINE-4-CARBOXYLIC ACID trifluoroacetate The 2-fluoro-5-methoxyphenylacetic acid (2.30 g, 12.5 mmol) was mixed with A- AMINOMETHYL- (3, 4-dimethoxy) benzene acetic acid ethyl ester (A-AMINOMETHYL-3, 4- dimethoxybenzene-acetic acid ethyl ester hydrochloride (3.62 g) in 100 ml of methylene chloride. To this suspension was added triethylamine (3.5 ml), HOBT (1.68 g) and EDCI (2.52 g, 1.05 eq). The mixture was stirred at room temperature for 12 hrs. The mixture was extracted with IN hydrochloric acid and methylene chloride. The organic layer was washed with sodium bicarbonate solution and then dried. After the evaporation of solvents, a crude oil was obtained (5.25 g).
  • 2
  • [ 798563-50-5 ]
  • C11H13FO3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: 2-(2-fluoro-5-methoxyphenyl)acetic acid With hydrogenchloride; ethanol at 80℃; Stage #2: With hydrogenchloride In water 62 Reference Example 62 ; Ethyl (2-fluoro-5-hydroxyphenyl)acetate [] A mixture of (2-fluoro-5-methoxyphenyl)acetonitrile (1.91 g), sodium hydroxide (2.3 g), water (7 ml) and ethanol (30 ml) were stirred at 80°C overnight. The solvent of the reaction solution was distilled off under reduced pressure and diluted with water. The reaction solution was acidified with dilute hydrochloric acid and twice extracted with ethyl acetate. The collected organic layer was dried over anhydrous sodium sulfate and the solvent was distilled off under reduced pressure to obtain an oily matter. The obtained oily matter was dissolved in ethanol (40 ml) and concentrated hydrochloric acid (0.5 ml) was added. The reaction mixture was stirred at 80°C overnight. The reaction solution was diluted with water and twice extracted with ethyl acetate. The collected organic layer was dried over anhydrous sodium sulfate and the solvent was distilled off under reduced pressure to obtain an oily matter. To a suspension of aluminum chloride (3.9 g) in toluene (30 ml) was added 1-octanethiol (13.5 g) at room temperature and the mixture was stirred for 0.5 hour. A solution of the obtained oily matter in toluene (20 ml) was added at room temperature and the mixture was stirred at room temperature for 2 hours. The reaction solution was poured into iced water and twice extracted with ethyl acetate. The collected organic layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained crude product was purified by silica gel column chromatography (hexane to hexane : ethyl acetate = 3 : 1) to obtain an objective product (1.84 g) as a solid matter. Melting point 85 - 87°C; 1H-NMR (CDCl3) δ 1.27 (3H, t), 3.61 (2H, d), 4.19 (2H, q), 5.00 (1H, s), 6.65-6.73 (2H, m), 6.91 (1H, t).
  • 3
  • [ 672931-28-1 ]
  • [ 798563-50-5 ]
YieldReaction ConditionsOperation in experiment
Stage #1: 2-(2-fluoro-5-methoxyphenyl)acetonitrile With sodium hydroxide; ethanol; water at 80℃; Stage #2: With hydrogenchloride In water 62 Reference Example 62 ; Ethyl (2-fluoro-5-hydroxyphenyl)acetate [] A mixture of (2-fluoro-5-methoxyphenyl)acetonitrile (1.91 g), sodium hydroxide (2.3 g), water (7 ml) and ethanol (30 ml) were stirred at 80°C overnight. The solvent of the reaction solution was distilled off under reduced pressure and diluted with water. The reaction solution was acidified with dilute hydrochloric acid and twice extracted with ethyl acetate. The collected organic layer was dried over anhydrous sodium sulfate and the solvent was distilled off under reduced pressure to obtain an oily matter. The obtained oily matter was dissolved in ethanol (40 ml) and concentrated hydrochloric acid (0.5 ml) was added. The reaction mixture was stirred at 80°C overnight. The reaction solution was diluted with water and twice extracted with ethyl acetate. The collected organic layer was dried over anhydrous sodium sulfate and the solvent was distilled off under reduced pressure to obtain an oily matter. To a suspension of aluminum chloride (3.9 g) in toluene (30 ml) was added 1-octanethiol (13.5 g) at room temperature and the mixture was stirred for 0.5 hour. A solution of the obtained oily matter in toluene (20 ml) was added at room temperature and the mixture was stirred at room temperature for 2 hours. The reaction solution was poured into iced water and twice extracted with ethyl acetate. The collected organic layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained crude product was purified by silica gel column chromatography (hexane to hexane : ethyl acetate = 3 : 1) to obtain an objective product (1.84 g) as a solid matter. Melting point 85 - 87°C; 1H-NMR (CDCl3) δ 1.27 (3H, t), 3.61 (2H, d), 4.19 (2H, q), 5.00 (1H, s), 6.65-6.73 (2H, m), 6.91 (1H, t).
With sodium hydroxide In water at 100℃; for 8h; 248.A Step A:2-(2-fluoro-5-methoxyphenyl)acetic acid Step A: 2-(2-fluoro-5-methoxyphenyl)acetic acid The solution of 2-(2-fluoro-5-methoxyphenyl)acetonitrile (200 mg, 1.0 mmol) and sodium hydroxide (81.5 mg, 2.0 mmol) in water was stirred at 100 degree for 8 h. The reaction mixture was evaporated under reduced pressure to get the crude product for the next step without further purification. LC-MS: m/z (M-H)=183.2
With water; sodium hydroxide at 100℃; for 8h; 7.A Step A 2-(2-fluoro-5-methoxyphenyl)acetic acid Step A 2-(2-fluoro-5-methoxyphenyl)acetic acid The solution of 2-(2-fluoro-5-methoxyphenyl)acetonitrile (200 mg, 1.0 mmol) and sodium hydroxide (81.5 mg, 2.0 mmol) in water was stirred at 100 degree for 8 h. The reaction mixture was evaporated under reduced pressure to get the crude product for the next step without further purification. LC-MS : m/z (M-H)= 183.2
With water; sodium hydroxide at 100℃; for 8h; A Step A methoxyphenyl)acetic acid Step A methoxyphenyl)acetic acid The solution of 2-(2-fluoro-5-methoxyphenyl)acetonitrile (200 mg, 1.0 mmol) and sodium hydroxide (81.5 mg, 2.0 mmol) in water was stirred at 100 degree for 8 h. The reaction mixture was evaporated under reduced pressure to get the crude product for the next step without further purification. LC-MS : m/z (M-H)= 183.2

  • 4
  • [ 2338-54-7 ]
  • [ 143-33-9 ]
  • [ 798563-50-5 ]
YieldReaction ConditionsOperation in experiment
68% The <strong>[2338-54-7]<strong>[2338-54-7]4-fluoro-3-methylanisol</strong>e</strong> (7.32 g, 52.28 mmol) was dissolved in 30 ml of carbon tetrachloride. To this solution was added N-bromosuccinimide (9.772 g, 1.05 eq) and A1 EN 428 mg, 5% eq). The mixture was refluxed for 1 hr and then cooled. The solid was filtered out and the filtrate was evaporated. The residue was extracted with ethyl acetate and washed with concentrated sodium bicarbonate. The organic layer was dried and solvents were removed to give an oil (13.0 g). The crude oil was dissolved in 150 ml of ethanol and sodium cyanide (12.8 g, 261 mmol) was added followed by the addition of water (20 ml). The mixture was refluxed for 2.5 hrs. The insoluble material was filtered out and the filtrate was concentrated. The residue was extracted with water and ether. The organic layer was dried and solvents were evaporated to give an oil (8.0 g). This oil was dissolved in 120 ml of ethanol. To that solution was added water (40 ml) and solid sodium hydroxide (20.9 g, 10.0 eq). The mixture was refluxed overnight to give a clear solution. Solvents were evaporated and the residue was suspended in 200 ml of hot water. The solution was cooled down and extracted with ether twice. The aqueous layer was acidified with 6N hydrochloric acid and then extracted with ether. The organic layer was washed with brine and dried. After the evaporation of solvents, 2-fluoro-5-methoxyphenylacetic acid was obtained (6.56 g, 68% in three steps).
  • 5
  • [ 1418126-43-8 ]
  • [ 798563-50-5 ]
YieldReaction ConditionsOperation in experiment
3.1 g With sodium tetrahydroborate; diphenyl diselenide; sodium hydroxide In ethanol at 20 - 40℃; Inert atmosphere;
  • 6
  • [ 105728-90-3 ]
  • [ 798563-50-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: potassium hydroxide / methanol; N,N-dimethyl-formamide / 2 h / -10 °C / Inert atmosphere 1.2: 0.5 h / -10 °C / pH 1 / Inert atmosphere 2.1: sodium hydroxide; sodium tetrahydroborate; diphenyl diselenide / ethanol / 20 - 40 °C / Inert atmosphere
  • 7
  • [ 798563-50-5 ]
  • 2-(2-fluoro-5-hydroxyphenyl)acetic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
With bromic acid In water at 105℃; for 5h;
With boron tribromide In dichloromethane at 20℃; 1 A solution of 2-(2-fluoro-5-methoxy-phenyl)acetic acid (2.0 g, 10.86 mmol) in DCM (30 ml_) and 1 M BBr3 in DCM (21.72 ml_, 21.72 mmol) was stirred at room temperature overnight. A further portion of 1 M BBr3 in DCM (21.72 ml_, 21.72 mmol) was added and the reaction mixture was stirred at room temperature over the weekend. The resulting precipitate was filtered, washed with DCM (100 ml_) and dried in vacuo to afford the title compound as a pale yellow solid. (1664) LC-MS (Method G): Rt 0.52 min; MS m/z 339.1 = [2M-H]- (85% 215 nm) (1665) 1H NMR (500 MHz, DMSO-d6) d 12.37 (s, 1 H), 9.30 (s, 1 H), 6.94 (t, J = 9.1 Hz, 1 H), 6.72 - 6.65 (m, 1 H), 6.67 - 6.59 (m, 1 H), 3.50 (s, 2H).
  • 8
  • [ 798563-50-5 ]
  • [ 459215-67-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: bromic acid / water / 5 h / 105 °C 2: sodium iodide; potassium hydroxide / ethanol / 20 °C
  • 9
  • [ 798563-50-5 ]
  • [ 1418126-44-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: bromic acid / water / 5 h / 105 °C 2: sodium iodide; potassium hydroxide / ethanol / 20 °C 3: oxalyl dichloride; N,N-dimethyl-formamide / toluene / 3 h / Inert atmosphere
  • 10
  • [ 798563-50-5 ]
  • [ 1418126-21-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: bromic acid / water / 5 h / 105 °C 2.1: sodium iodide; potassium hydroxide / ethanol / 20 °C 3.1: oxalyl dichloride; N,N-dimethyl-formamide / toluene / 3 h / Inert atmosphere 4.1: sodium hydroxide / chloroform; water / 16 h / 20 °C / Cooling with ice 5.1: trichlorophosphate / acetonitrile / 3 h / Reflux; Inert atmosphere 5.2: 16 h / 20 °C / Inert atmosphere; Cooling with ice 6.1: acetic acid; hydrogen; palladium on activated charcoal / methanol / 16 h / 760.05 Torr
  • 11
  • [ 798563-50-5 ]
  • [ 1418126-45-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: bromic acid / water / 5 h / 105 °C 2: sodium iodide; potassium hydroxide / ethanol / 20 °C 3: oxalyl dichloride; N,N-dimethyl-formamide / toluene / 3 h / Inert atmosphere 4: sodium hydroxide / chloroform; water / 16 h / 20 °C / Cooling with ice
  • 12
  • [ 798563-50-5 ]
  • [ 1418126-47-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: bromic acid / water / 5 h / 105 °C 2.1: sodium iodide; potassium hydroxide / ethanol / 20 °C 3.1: oxalyl dichloride; N,N-dimethyl-formamide / toluene / 3 h / Inert atmosphere 4.1: sodium hydroxide / chloroform; water / 16 h / 20 °C / Cooling with ice 5.1: trichlorophosphate / acetonitrile / 3 h / Reflux; Inert atmosphere 5.2: 16 h / 20 °C / Inert atmosphere; Cooling with ice
  • 13
  • [ 51-17-2 ]
  • [ 798563-50-5 ]
  • 3-methoxy-11H-benzo[4,5]imidazo[1,2-a]indol-11-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
50% With boron trifluoride diethyl etherate; oxygen; copper diacetate; potassium carbonate In N,N-dimethyl-formamide at 120℃; for 20h; Sealed tube; chemoselective reaction;
  • 14
  • [ 798563-50-5 ]
  • 1-(2-fluoro-5-methoxybenzoyl)-6,7-dimethoxyisoquinoline-4-caboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine / dichloromethane / 12 h / 20 °C 2: phosphorus pentachloride / dichloromethane / 2.5 h / 20 °C 3: sulfur / 0.33 h / 165 °C 4: selenium(IV) oxide / ethyl acetate / 1 h / Heating / reflux 5: sodium hydroxide / methanol; water / 0.5 h / Heating / reflux
  • 15
  • [ 798563-50-5 ]
  • 1-(2-fluoro-5-methoxybenzoyl)-6,7-dimethoxyisoquinoline-4-caboxylic acid ethyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine / dichloromethane / 12 h / 20 °C 2: phosphorus pentachloride / dichloromethane / 2.5 h / 20 °C 3: sulfur / 0.33 h / 165 °C 4: selenium(IV) oxide / ethyl acetate / 1 h / Heating / reflux
  • 16
  • [ 798563-50-5 ]
  • 1-(2-fluoro-5-methoxybenzoyl)-4-N-BOC-aminomethyl-6,7-dimethoxyisoquinoline [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 8 steps 1.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine / dichloromethane / 12 h / 20 °C 2.1: phosphorus pentachloride / dichloromethane / 2.5 h / 20 °C 3.1: sulfur / 0.33 h / 165 °C 4.1: lithium aluminium tetrahydride / tetrahydrofuran / 0 - 20 °C 5.1: methanesulfonyl chloride; triethylamine / dichloromethane / 2 h / 0 °C 5.2: 20 °C 6.1: sodium azide / dimethyl sulfoxide / 2 h / 65 °C 7.1: sodium azide; hydrogen / palladium 10% on activated carbon / tetrahydrofuran / 2 h / 2068.65 Torr 8.1: selenium(IV) oxide / ethyl acetate / 3 h / Heating / reflux
  • 17
  • [ 798563-50-5 ]
  • hydrochloride salt (4-aminomethyl-6,7-dimethoxy-isoquinolin-1-yl)-(2-fluoro-5-methoxy-phenyl)-methanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 9 steps 1.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine / dichloromethane / 12 h / 20 °C 2.1: phosphorus pentachloride / dichloromethane / 2.5 h / 20 °C 3.1: sulfur / 0.33 h / 165 °C 4.1: lithium aluminium tetrahydride / tetrahydrofuran / 0 - 20 °C 5.1: methanesulfonyl chloride; triethylamine / dichloromethane / 2 h / 0 °C 5.2: 20 °C 6.1: sodium azide / dimethyl sulfoxide / 2 h / 65 °C 7.1: sodium azide; hydrogen / palladium 10% on activated carbon / tetrahydrofuran / 2 h / 2068.65 Torr 8.1: selenium(IV) oxide / ethyl acetate / 3 h / Heating / reflux 9.1: trifluoroacetic acid / dichloromethane; water / 2 h / 20 °C
  • 18
  • [ 798563-50-5 ]
  • [ 798563-56-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine / dichloromethane / 12 h / 20 °C 2.1: phosphorus pentachloride / dichloromethane / 2.5 h / 20 °C 3.1: sulfur / 0.33 h / 165 °C 4.1: lithium aluminium tetrahydride / tetrahydrofuran / 0 - 20 °C 5.1: methanesulfonyl chloride; triethylamine / dichloromethane / 2 h / 0 °C 5.2: 20 °C
  • 19
  • [ 798563-50-5 ]
  • [ 798563-55-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine / dichloromethane / 12 h / 20 °C 2: phosphorus pentachloride / dichloromethane / 2.5 h / 20 °C 3: sulfur / 0.33 h / 165 °C 4: lithium aluminium tetrahydride / tetrahydrofuran / 0 - 20 °C
  • 20
  • [ 798563-50-5 ]
  • [ 798563-57-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine / dichloromethane / 12 h / 20 °C 2.1: phosphorus pentachloride / dichloromethane / 2.5 h / 20 °C 3.1: sulfur / 0.33 h / 165 °C 4.1: lithium aluminium tetrahydride / tetrahydrofuran / 0 - 20 °C 5.1: methanesulfonyl chloride; triethylamine / dichloromethane / 2 h / 0 °C 5.2: 20 °C 6.1: sodium azide / dimethyl sulfoxide / 2 h / 65 °C
  • 21
  • [ 798563-50-5 ]
  • [ 798563-51-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine / dichloromethane / 12 h / 20 °C 2: phosphorus pentachloride / dichloromethane / 2.5 h / 20 °C 3: sulfur / 0.33 h / 165 °C
  • 22
  • [ 798563-50-5 ]
  • [ 1344688-82-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine / dichloromethane / 12 h / 20 °C 2: phosphorus pentachloride / dichloromethane / 2.5 h / 20 °C
  • 23
  • [ 798563-50-5 ]
  • C25H29FN2O5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine / dichloromethane / 12 h / 20 °C 2.1: phosphorus pentachloride / dichloromethane / 2.5 h / 20 °C 3.1: sulfur / 0.33 h / 165 °C 4.1: lithium aluminium tetrahydride / tetrahydrofuran / 0 - 20 °C 5.1: methanesulfonyl chloride; triethylamine / dichloromethane / 2 h / 0 °C 5.2: 20 °C 6.1: sodium azide / dimethyl sulfoxide / 2 h / 65 °C 7.1: sodium azide; hydrogen / palladium 10% on activated carbon / tetrahydrofuran / 2 h / 2068.65 Torr
  • 24
  • [ 798563-50-5 ]
  • 2-(4-tert-butyl-2-fluoro-5-methoxyphenyl)acetic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: sulfuric acid / 1,2-dichloro-ethane 1.2: 0.67 h / Reflux 2.1: water; lithium hydroxide / tetrahydrofuran / 1 h
Multi-step reaction with 2 steps 1.1: sulfuric acid / 1,2-dichloro-ethane / 1 h 1.2: 0.67 h / Reflux 2.1: water; lithium hydroxide / tetrahydrofuran / 1 h
  • 25
  • [ 798563-50-5 ]
  • 2-(4-tert-butyl-2-fluoro-5-hydroxyphenyl)acetic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: sulfuric acid / 1,2-dichloro-ethane 1.2: 0.67 h / Reflux 2.1: water; lithium hydroxide / tetrahydrofuran / 1 h 3.1: boron tribromide / dichloromethane / 72 h / 0 - 20 °C
  • 26
  • [ 798563-50-5 ]
  • methyl 5-[[2-(4-tert-butyl-2-fluoro-5-hydroxyphenyl)acetyl]amino]thiophene-2-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: sulfuric acid / 1,2-dichloro-ethane 1.2: 0.67 h / Reflux 2.1: water; lithium hydroxide / tetrahydrofuran / 1 h 3.1: boron tribromide / dichloromethane / 72 h / 0 - 20 °C 4.1: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 4 h / 20 °C
  • 27
  • [ 798563-50-5 ]
  • 5-[[2-(4-tert-butyl-2-fluoro-5-hydroxyphenyl)acetyl]amino]thiophene-2-carboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: sulfuric acid / 1,2-dichloro-ethane 1.2: 0.67 h / Reflux 2.1: water; lithium hydroxide / tetrahydrofuran / 1 h 3.1: boron tribromide / dichloromethane / 72 h / 0 - 20 °C 4.1: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 4 h / 20 °C 5.1: water; lithium hydroxide / tetrahydrofuran / 50 °C
  • 28
  • [ 798563-50-5 ]
  • 5-[[2-(4-tert-butyl-2-fluoro-5-hydroxyphenyl)acetyl]amino]-N-(1-cyano-1-methylethyl)thiophene-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: sulfuric acid / 1,2-dichloro-ethane 1.2: 0.67 h / Reflux 2.1: water; lithium hydroxide / tetrahydrofuran / 1 h 3.1: boron tribromide / dichloromethane / 72 h / 0 - 20 °C 4.1: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 4 h / 20 °C 5.1: water; lithium hydroxide / tetrahydrofuran / 50 °C 6.1: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 20 °C
  • 29
  • [ 798563-50-5 ]
  • 2-(4-bromo-2-fluoro-5-methoxyphenyl)acetic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: 2-(2-fluoro-5-methoxyphenyl)acetic acid With bromine In acetonitrile at 0 - 20℃; for 1.5h; Stage #2: With bromine In acetonitrile at 0 - 20℃; for 4h; Stage #3: With acetic acid In water at 0 - 20℃; for 4h; 1 To a cooled (0°C) solution of 2-(2-fluoro-5-methoxy-phenyl)acetic acid (45 g, 244.35 mmol) in MeCN (1200 ml_) was added dropwise a solution of bromine (12.63 ml_, 219.92 mmol) in MeCN (100 ml_) over a period of 10 mins. The mixture was allowed to warm to room temperature gradually without removing the ice bath (-1.5 h). A second portion of bromine (4.21 ml_, 73.31 mmol) in MeCN (50 ml_) was added dropwise at 0°C and stirring continued at room temperature for 3.5 h. A third portion of bromine (4.21 ml_, 73.31 mmol) in MeCN (50 ml_) was added at room temperature and stirring continued for 30 mins. The reaction was quenched carefully with sat. aq. sodium sulfite (-700 ml_) until the bright orange colour had disappeared. The colourless solution was diluted with brine (200 ml_) and EtOAc (200 ml_), stirred vigorously for 10 mins and then left to stand at room temperature overnight. The organic layer was separated and the aqueous layer was further extracted with EtOAc (200 ml_). The combined organic extracts were dried over Na2SC>4 and concentrated in vacuo to obtain the crude as a white solid. The solid was recrystallised by dissolving in AcOH (700 ml_) and treating with water (4 L). The mixture was stirred and kept at room temperature for 1 h and then at 0°C for 3 h. The resulting solid was filtered, washed with water (200 ml_) and dried at 40°C under vacuum to afford the title compound as a fluffy white solid. LC-MS (Method B): Rt 1.07 min; MS m/z 523.2/525.1/527.0 = [2M-H]- (99% 215 nm) 1 H NMR (500 MHz, DMSO-d6) d 12.55 (br. s, 1 H), 7.50 (d, J = 8.9 Hz, 1 H), 7.13 (d, J = 6.6 Hz, 1 H), 3.81 (s, 3H), 3.61 (d, J = 1.3 Hz, 2H).
With bromine In acetonitrile at 0 - 20℃; for 5.5h; 9.A1 Step A1 : 2-(4-Bro o-2-fluoro-5- ethoxy-phenyl)acetic acid To a cooled (0 C) solution of 2-(2-fluoro-5-methoxy-phenyl)acetic acid (45 g, 244.4 mmol) in MeCN (1.2 L) was added dropwise a solution of bromine (12.63 ml_, 219.9 mmol) in MeCN (100 ml_) over a period of 10 min. The resulting mixture was allowed to warm to room temperature gradually without removing the ice bath (-1.5 h). Additional bromine (4.21 ml_, 73.3 mmol) in MeCN (50 ml_) was added dropwise to the mixture at 0 °C which was stirred at room temperature for a further 3.5 h. Further bromine (4.21 ml_, 73.3 mmol) in MeCN (50 ml_) was added at room temperature and mixture was stirred at room temperature for 30 min. The reaction was quenched carefully with saturated aqueous sodium sulfite (-700 ml_) until the bright orange colour had disappeared. The colourless solution was diluted with brine (200 ml_) and EtOAc (200 ml_), stirred vigorously for 10 min. The organic layer was separated and the aqueous layer was extracted further with EtOAc (200 ml_). The organic layers were combined, dried over Na2S04 and concentrated in vacuo to obtain the crude product as a white solid. The crude product was recrystallised by dissolving the solid in AcOH (700 ml_), then treated with water (4 L). The mixture was stirred to mix the solvents whereupon crystals gradually appeared. The mixture was kept at room temperature for 1 h and then at 0 °C for 3 h. Filtration followed by vacuum drying at 40 °C afforded the title compound as a fluffy white solid. (0644) LC-MS (Method C): Rt 1.07min; (99% 215 nm) 1 H NMR (500 MHz, DMSO-d6) d 12.55 (br s, 1 H), 7.50 (d, J = 8.9 Hz, 1 H), 7.13 (d, J = 6.6 (0645) Hz, 1 H), 3.81 (s, 3H), 3.61 (d, J = 1.3 Hz, 2H).
With bromine In acetonitrile at 0 - 20℃; for 5.5h; 1 To a cooled (0 °C) solution of 2-(2-fluoro-5-methoxy-phenyl)acetic acid (45 g, 244.4 mmol) in MeCN (1.2 L) was added dropwise a solution of bromine (12.63 ml_, 244.9 mmol) in MeCN (100 ml_) over a period of 10 min. The resulting mixture was allowed to warm to room temperature gradually without removing the ice bath (-1.5 h). Additional bromine (4.21 ml_, 81.64 mmol) in MeCN (50 ml_) was added dropwise to the mixture at 0 °C which was stirred at room temperature for a further 3.5 h. Further bromine (4.21 ml_, 81.64 mmol) in MeCN (50 ml_) was added at room temperature and mixture was stirred at room temperature for 30 min. The reaction was quenched carefully with saturated aqueous sodium sulfite (-700 ml_) until the bright orange colour had disappeared. The colourless solution was diluted with brine (200 ml_) and EtOAc (200 ml_), stirred vigorously for 10 min. The organic layer was separated and the aqueous layer was extracted further with EtOAc (200 ml_). Organic layers were combined, dried over Na2S04 and concentrated in vacuo to obtain the crude product as a white solid. The crude product was recrystallised by dissolving the solid in AcOH (700 ml_), then treated with water (4 L). The mixture was stirred to mix the solvents whereupon crystals gradually appeared. The mixture was kept at room temperature for 1 h and then at 0 °C for 3 h. Filtration followed by vacuum drying at 40 °C afforded the title compound as a fluffy white solid. (1780) LC-MS (Method E): Rt 1.07min; (99% 215 nm) (1781) 1 H NMR (500 MHz, DMSO-d6) d 12.55 (br s, 1 H), 7.50 (d, J = 8.9 Hz, 1 H), 7.13 (d, J = 6.6 (1782) Hz, 1 H), 3.81 (s, 3H), 3.61 (d, J = 1.3 Hz, 2H).
  • 30
  • [ 798563-50-5 ]
  • benzyl 2-(4-bromo-2-fluoro-5-methoxyphenyl)acetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: bromine / acetonitrile / 5.5 h / 0 - 20 °C 2: potassium carbonate / N,N-dimethyl-formamide / 18 h / 20 °C
Multi-step reaction with 2 steps 1: bromine / acetonitrile / 5.5 h / 0 - 20 °C 2: potassium carbonate / N,N-dimethyl-formamide / 18 h / 20 °C
  • 31
  • [ 798563-50-5 ]
  • methyl 2-[4-(2-benzyloxy-2-oxoethyl)-5-fluoro-2-methoxyphenyl]-2-methylpropanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: bromine / acetonitrile / 5.5 h / 0 - 20 °C 2: potassium carbonate / N,N-dimethyl-formamide / 18 h / 20 °C 3: zinc(II) fluoride; bis(tri-t-butylphosphine)palladium(0) / N,N-dimethyl-formamide / 18 h / 80 °C / Inert atmosphere
Multi-step reaction with 3 steps 1: bromine / acetonitrile / 5.5 h / 0 - 20 °C 2: potassium carbonate / N,N-dimethyl-formamide / 18 h / 20 °C 3: zinc(II) fluoride; bis(tri-t-butylphosphine)palladium(0) / N,N-dimethyl-formamide / 18 h / 80 °C / Inert atmosphere
  • 32
  • [ 798563-50-5 ]
  • 2-(5-fluoro-3,3-dimethyl-2-oxo-benzofuran-6-yl)acetic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: bromine / acetonitrile / 5.5 h / 0 - 20 °C 2: potassium carbonate / N,N-dimethyl-formamide / 18 h / 20 °C 3: zinc(II) fluoride; bis(tri-t-butylphosphine)palladium(0) / N,N-dimethyl-formamide / 18 h / 80 °C / Inert atmosphere 4: boron tribromide / dichloromethane / 4.5 h / 0 - 20 °C
Multi-step reaction with 5 steps 1.1: bromine / acetonitrile / 1.5 h / 0 - 20 °C 1.2: 4 h / 0 - 20 °C 1.3: 4 h / 0 - 20 °C 2.1: boron tribromide / dichloromethane / 1 h / 0 - 20 °C / Inert atmosphere 3.1: potassium carbonate / N,N-dimethyl-formamide / 20 °C 4.1: zinc(II) fluoride / N,N-dimethyl-formamide / 20 - 80 °C / Inert atmosphere 5.1: boron tribromide / dichloromethane / 20 °C
Multi-step reaction with 4 steps 1: bromine / acetonitrile / 5.5 h / 0 - 20 °C 2: potassium carbonate / N,N-dimethyl-formamide / 18 h / 20 °C 3: zinc(II) fluoride; bis(tri-t-butylphosphine)palladium(0) / N,N-dimethyl-formamide / 18 h / 80 °C / Inert atmosphere 4: boron tribromide / dichloromethane / 4.5 h / 0 - 20 °C
  • 33
  • [ 798563-50-5 ]
  • 5-[[2-[2-fluoro-5-hydroxy-4-(2-hydroxy-1,1-dimethyl-ethyl)phenyl]acetyl]amino]-N-[1-(trifluoromethyl)cyclopropyl]thiophene-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: bromine / acetonitrile / 5.5 h / 0 - 20 °C 2.1: potassium carbonate / N,N-dimethyl-formamide / 18 h / 20 °C 3.1: zinc(II) fluoride; bis(tri-t-butylphosphine)palladium(0) / N,N-dimethyl-formamide / 18 h / 80 °C / Inert atmosphere 4.1: boron tribromide / dichloromethane / 4.5 h / 0 - 20 °C 5.1: 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide; ethyl acetate / 0.5 h / 20 °C 5.2: 1 h / -78 - 20 °C
  • 34
  • [ 67-56-1 ]
  • [ 798563-50-5 ]
  • [ 75-65-0 ]
  • C14H19FO3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: 2-(2-fluoro-5-methoxyphenyl)acetic acid; <i>tert</i>-butyl alcohol With sulfuric acid In 1,2-dichloro-ethane for 1h; Stage #2: methanol With hydrogenchloride for 0.666667h; Reflux; 21.1 Step 1 : 2-(4-te/f-Butyl-2-fluoro-5-methoxy-phenyl)acetic acid A solution of 2-(2-fluoro-5-methoxy-phenyl)acetic acid (5.0 g, 27.15 mmol) in DCE (181 ml_) was treated with te/f-butanol (31.16 ml_, 325.8 mmol) and concentrated sulfuric acid (17.37 ml_, 325.8 mmol). After 1 hour, additional te/f-butanol (10.0 ml_, 105 mmol) and concentrated sulfuric acid (5.8 ml_, 109 mmol) were added and the reaction was stirred overnight. The resulting mixture was diluted with water (150 ml_) and the phases were separated. The aqueous layer was extracted with DCM (3 x 150 ml_). The combined organic extracts were washed with brine, dried over Na2SC>4 and concentrated in vacuo. The crude residue was diluted with MeOH (100 ml_) and treated with 2M HCI in MeOH (100 ml_, freshly prepared from thionyl chloride). The reaction mixture was heated at reflux for 40 mins. The resulting mixture was then cooled to room temperature and concentrated in vacuo. The residue was dissolved in DCM (150 ml_) and washed with saturated aqueous sodium bicarbonate solution (150 ml_). The organic layer was separated and the aqueous portion was further extracted with DCM (3 x 100 ml_). The organic extracts were combined, dried over Na2SC>4 and concentrated in vacuo. Purification by column chromatography on silica, eluting with 0-10% EtOAc in heptanes, afford the methyl ester of the desired product. The material was dissolved in a mixture of 1 M aq. LiOH (80 ml_) and THF (80 ml_) and stirred for 1 hour. The volatiles were then removed in vacuo , and the aqueous solution was acidified with 1 M HCI, which resulted in precipitation of the desired product. The solids were obtained by filtration, washed with excess water and dried to afford 2-(4-te/f-butyl-2-fluoro-5-methoxy-phenyl)acetic acid (5.22 g, 21.3 mmol, 78% yield) as a pale yellow solid. 1 H NMR (500 MHz, DMSO-d6) d 6.93 (d, J = 6.1 Hz, 1 H), 6.92 (s, 1 H), 3.77 (s, 3H), 3.54 (s, 2H), 1.31 (s, 9H).
Stage #1: 2-(2-fluoro-5-methoxyphenyl)acetic acid; <i>tert</i>-butyl alcohol With sulfuric acid In 1,2-dichloro-ethane Stage #2: methanol With hydrogenchloride for 0.666667h; Reflux; 8.1 Step 1 : 2-(4-te/f-Butyl-2-fluoro-5-methoxy-phenyl)acetic acid A solution of 2-(2-fluoro-5-methoxy-phenyl)acetic acid (5.0 g, 27.15 mmol) in DCE (181.01 ml_) was treated with te/f-butanol (31.16 ml_, 325.8 mmol) and concentrated sulfuric acid (17.37 ml_, 325.8 mmol). After stirring for 1 h, additional te/f-butanol (10.0 ml_, 105 mmol) and concentrated sulfuric acid (5.8 ml_, 109 mmol) were added and the mixture was stirred overnight. The resulting mixture was diluted with water (150 ml_) and the phases were separated. The aqueous layer was extracted with DCM (3 x 150 ml_). The combined organic extracts were washed with brine, dried over Na2SC>4 and concentrated in vacuo. The residue was diluted with MeOH (100 ml_) and treated with 2M HCI in MeOH (100 ml_, freshly prepared from thionyl chloride) and the mixture was heated at reflux for 40 min. The resulting mixture was concentrated in vacuo and the residue was dissolved in DCM (150 ml_), washing with saturated aqueous sodium bicarbonate solution (150 ml_). The aqueous washes were further extracted with DCM (3 x 100 ml_) and the combined organic extracts were dried over Na2SC>4 and concentrated in vacuo. Purification by chromatography on silica eluting with 0-10% EtOAc in heptanes afforded the methyl ester intermediate. The material was dissolved in 1M LiOH (80 ml_) and THF (80 ml_) and stirred for 1 h. The volatiles were removed in vacuo and the aqueous solution was acidified with HCI resulting in precipitation of a solid. The solid was washed with excess water and dried to afford the title compound as a pale-yellow solid. (0619) LC-MS (Method C): Rt 1.16 min; no ionisation (98% 215nm) (0620) 1 H NMR (500 MHz, DMSO-d6) d 6.93 (d, J = 6.1 Hz, 1 H), 6.92 (s, 1 H), 3.77 (s, 3H), 3.54 (s, 2H), 1.31 (s, 9H).
  • 35
  • [ 798563-50-5 ]
  • 1-bromo-3-(4-tert-butyl-2-fluoro-5-methoxyphenyl)propan-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: sulfuric acid / 1,2-dichloro-ethane / 1 h 1.2: 0.67 h / Reflux 2.1: water; lithium hydroxide / tetrahydrofuran / 1 h 3.1: thionyl chloride; N,N-dimethyl-formamide / dichloromethane / 1 h / 20 °C 3.2: 2 h / 0 - 20 °C 3.3: 1 h / 0 - 20 °C
  • 36
  • [ 798563-50-5 ]
  • methyl 2-[(4-tert-butyl-2-fluoro-5-methoxyphenyl)methyl]imidazo[1,2-a]pyridine-7-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: sulfuric acid / 1,2-dichloro-ethane / 1 h 1.2: 0.67 h / Reflux 2.1: water; lithium hydroxide / tetrahydrofuran / 1 h 3.1: thionyl chloride; N,N-dimethyl-formamide / dichloromethane / 1 h / 20 °C 3.2: 2 h / 0 - 20 °C 3.3: 1 h / 0 - 20 °C 4.1: potassium iodide / 1,2-dichloro-ethane / 4 h / 100 °C
  • 37
  • [ 798563-50-5 ]
  • 2-[(4-tert-butyl-2-fluoro-5-methoxyphenyl)methyl]imidazo[1,2-a]pyridine-7-carboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: sulfuric acid / 1,2-dichloro-ethane / 1 h 1.2: 0.67 h / Reflux 2.1: water; lithium hydroxide / tetrahydrofuran / 1 h 3.1: thionyl chloride; N,N-dimethyl-formamide / dichloromethane / 1 h / 20 °C 3.2: 2 h / 0 - 20 °C 3.3: 1 h / 0 - 20 °C 4.1: potassium iodide / 1,2-dichloro-ethane / 4 h / 100 °C 5.1: lithium hydroxide / tetrahydrofuran / 5 h / 40 - 50 °C
  • 38
  • [ 798563-50-5 ]
  • 2-[(4-tert-butyl-2-fluoro-5-methoxyphenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]imidazo[1,2-a]pyridine-7-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: sulfuric acid / 1,2-dichloro-ethane / 1 h 1.2: 0.67 h / Reflux 2.1: water; lithium hydroxide / tetrahydrofuran / 1 h 3.1: thionyl chloride; N,N-dimethyl-formamide / dichloromethane / 1 h / 20 °C 3.2: 2 h / 0 - 20 °C 3.3: 1 h / 0 - 20 °C 4.1: potassium iodide / 1,2-dichloro-ethane / 4 h / 100 °C 5.1: lithium hydroxide / tetrahydrofuran / 5 h / 40 - 50 °C 6.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / N,N-dimethyl-formamide / 4 h / 20 - 40 °C
  • 39
  • [ 798563-50-5 ]
  • 2-[(4-tert-butyl-2-fluoro-5-hydroxyphenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]imidazo[1,2-a]pyridine-7-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1.1: sulfuric acid / 1,2-dichloro-ethane / 1 h 1.2: 0.67 h / Reflux 2.1: water; lithium hydroxide / tetrahydrofuran / 1 h 3.1: thionyl chloride; N,N-dimethyl-formamide / dichloromethane / 1 h / 20 °C 3.2: 2 h / 0 - 20 °C 3.3: 1 h / 0 - 20 °C 4.1: potassium iodide / 1,2-dichloro-ethane / 4 h / 100 °C 5.1: lithium hydroxide / tetrahydrofuran / 5 h / 40 - 50 °C 6.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / N,N-dimethyl-formamide / 4 h / 20 - 40 °C 7.1: boron tribromide / dichloromethane / 3 h / 20 °C
  • 40
  • [ 798563-50-5 ]
  • 2-(4-bromo-2-fluoro-5-hydroxyphenyl)acetic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: bromine / acetonitrile / 1.5 h / 0 - 20 °C 1.2: 4 h / 0 - 20 °C 1.3: 4 h / 0 - 20 °C 2.1: boron tribromide / dichloromethane / 1 h / 0 - 20 °C / Inert atmosphere
Multi-step reaction with 2 steps 1: bromine / acetonitrile / 5.5 h / 0 - 20 °C 2: boron tribromide / dichloromethane / 3.5 h / 0 - 20 °C
  • 41
  • [ 798563-50-5 ]
  • benzyl 2-(5-benzyloxy-4-bromo-2-fluorophenyl)acetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: bromine / acetonitrile / 1.5 h / 0 - 20 °C 1.2: 4 h / 0 - 20 °C 1.3: 4 h / 0 - 20 °C 2.1: boron tribromide / dichloromethane / 1 h / 0 - 20 °C / Inert atmosphere 3.1: potassium carbonate / N,N-dimethyl-formamide / 20 °C
  • 42
  • [ 798563-50-5 ]
  • methyl 2-[2-benzyloxy-4-(2-benzyloxy-2-oxoethyl)-5-fluorophenyl]-2-methylpropanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: bromine / acetonitrile / 1.5 h / 0 - 20 °C 1.2: 4 h / 0 - 20 °C 1.3: 4 h / 0 - 20 °C 2.1: boron tribromide / dichloromethane / 1 h / 0 - 20 °C / Inert atmosphere 3.1: potassium carbonate / N,N-dimethyl-formamide / 20 °C 4.1: zinc(II) fluoride / N,N-dimethyl-formamide / 20 - 80 °C / Inert atmosphere
  • 43
  • [ 798563-50-5 ]
  • methyl 2-[(4-tert-butyl-2-fluoro-5-methoxyphenyl)methyl]-1H-benzimidazole-5-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: sulfuric acid / 1,2-dichloro-ethane / 1 h 1.2: 0.67 h / Reflux 2.1: water; lithium hydroxide / tetrahydrofuran / 1 h 3.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / N,N-dimethyl-formamide / 3 h / 20 °C
  • 44
  • [ 798563-50-5 ]
  • 2-[(4-tert-butyl-2-fluoro-5-methoxyphenyl)methyl]-1H-benzimidazole-5-carboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: sulfuric acid / 1,2-dichloro-ethane / 1 h 1.2: 0.67 h / Reflux 2.1: water; lithium hydroxide / tetrahydrofuran / 1 h 3.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / N,N-dimethyl-formamide / 3 h / 20 °C 4.1: lithium hydroxide; methanol / tetrahydrofuran / 20 °C
  • 45
  • [ 798563-50-5 ]
  • 2-[(4-tert-butyl-2-fluoro-5-methoxyphenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]-1H-benzimidazole-5-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: sulfuric acid / 1,2-dichloro-ethane / 1 h 1.2: 0.67 h / Reflux 2.1: water; lithium hydroxide / tetrahydrofuran / 1 h 3.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / N,N-dimethyl-formamide / 3 h / 20 °C 4.1: lithium hydroxide; methanol / tetrahydrofuran / 20 °C 5.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / N,N-dimethyl-formamide / 20 °C
  • 46
  • [ 798563-50-5 ]
  • 2-[(4-tert-butyl-2-fluoro-5-hydroxyphenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]-1H-benzimidazole-5-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: sulfuric acid / 1,2-dichloro-ethane / 1 h 1.2: 0.67 h / Reflux 2.1: water; lithium hydroxide / tetrahydrofuran / 1 h 3.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / N,N-dimethyl-formamide / 3 h / 20 °C 4.1: lithium hydroxide; methanol / tetrahydrofuran / 20 °C 5.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / N,N-dimethyl-formamide / 20 °C 6.1: boron tribromide / dichloromethane / 2 h / 20 °C
  • 47
  • [ 798563-50-5 ]
  • 2-(4-tert-butyl-2-fluoro-5-methoxyphenyl)-N-[2-[1-(trifluoromethyl)cyclopropyl]-1H-benzimidazol-5-yl]acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: sulfuric acid / 1,2-dichloro-ethane / 1 h 1.2: 0.67 h / Reflux 2.1: water; lithium hydroxide / tetrahydrofuran / 1 h 3.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / N,N-dimethyl-formamide / 1.5 h / 20 °C
  • 48
  • [ 798563-50-5 ]
  • [ 75-65-0 ]
  • 2-(4-tert-butyl-2-fluoro-5-methoxyphenyl)acetic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sulfuric acid for 3h; 2-(4-ferf-Butyl-2-fluoro-5-methoxy-phenyl)acetic acid 2-(2-Fluoro-5-methoxy-phenyl)acetic acid (585 mg, 3.17 mmol) was treated with concentrated sulfuric acid (677 pL, 12.7 mmol) and te/f-butanol (1.21 mL, 12.7 mmol) and stirred for 3 h. The reaction mixture was concentrated in vacuo. During transfer of material MeOH was used, which resulted in the formation of the methyl ester. The residue was purified by C18 reverse phase chromatography eluting with 10-100% MeCN in water. The resulting material was dissolved in 2M LiOH (7 mL) and THF (7 mL) and stirred for 2 h. The volatile solvents were removed in vacuo and the aqueous solution was acidified with 1 M HCI. The suspension was extracted with DCM (3 x 20 ml_) and the combined organic extracts were dried over Na2SC>4 and concentrated in vacuo to afford the title compound as a pale yellow solid. (1563) LC-MS (Method E): Rt 1.17 mins; MS m/z 239.0 = [M-H]- (96% 215 nm) (1564) 1 H NMR (500 MHz, DMSO-d6) d 12.42 (s, 1 H), 6.94 (d, J = 7.0 Hz, 1 H), 6.92 (d, J = 1.9 Hz, 1 H), 3.77 (s, 3H), 3.57 - 3.53 (m, 2H), 1.31 (s, 9H).
  • 49
  • [ 71469-93-7 ]
  • [ 798563-50-5 ]
  • methyl 4-[[2-(2-fluoro-5-methoxyphenyl)acetyl]amino]pyridine-2-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In 1,4-dioxane; ethyl acetate for 2h; 5.1 Step 1 : Methyl 4-[[2-(2-fluoro-5-methoxy-phenyl)acetyl]amino]pyridine-2-carboxylate To a solution of methyl 4-aminopyridine-2-carboxylate (3.64 g, 23.89 mmol) and 2-(2- fluoro-5-methoxy-phenyl)acetic acid (4 g, 21.72 mmol) in 1 ,4-dioxane (108.6 ml_) was added TEA (9.48 ml_, 54.3 mmol) and 50% T3P solution in EtOAc (51.67 ml_, 43.44 mmol) and the mixture was stirred for 2 h. The resulting mixture was concentrated in vacuo and the residue was dissolved in EtOAc (100 ml_) and washed with saturated aqueous sodium bicarbonate (2 x 100 ml_). The organic portion was dried over Na2S04 and concentrated in vacuo. Purification by chromatography on silica eluting with 0%-100% EtOAc in heptanes afforded the title compound as an orange gum. (0943) LC-MS (Method E): Rt 1.00 mins; MS m/z 319.1 = [M+H]+ (100% 215 nm) (0944) 1 H NMR (500 MHz, DMSO-d6) d 10.80 (s, 1 H), 8.55 (d, J = 5.4 Hz, 1 H), 8.30 (d, J = 1.8 Hz, 1 H), 7.77 (dd, J = 5.5, 2.2 Hz, 1 H), 7.1 1 (t, J = 9.2 Hz, 1 H), 6.96 (dd, J = 6.1 , 3.2 Hz, 1 H), 6.86 (dt, J = 8.9, 3.7 Hz, 1 H), 3.87 (s, 3H), 3.77 (s, 2H), 3.73 (s, 3H).
  • 50
  • [ 798563-50-5 ]
  • [ 53001-22-2 ]
  • 2-[2-deuterio-6-fluoro-3-methoxy-4-[2,2,2-trideuterio-1,1-bis(trideuteriomethyl)ethyl]phenyl]acetic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sulfuric acid-d2 In 1,2-dichloro-ethane at 20℃; for 3h; 4.1 Step 1 : 2-[2-Deuterio-6-fluoro-3-methoxy-4-[2,2,2-trideuterio-1 ,1-bis(trideuterio methyl) ethyl]phenyl]acetic acid A vessel containing 2-(2-fluoro-5-methoxy-phenyl)acetic acid (300 g, 1.63 mmol) in DCE (16 ml_) was treated with 1 ,1 , 1 ,3,3, 3-hexadeuterio-2-deuteriooxy-2- (trideuteriomethyl) propane (1.23 ml_, 13.03 mmol) and deuterosulfuric acid (0.71 ml_, 13.03 mmol) then stirred at room temperature for 3 h. The resulting mixture was diluted with water (20 ml_) and the layers separated. The aqueous layer was extracted with DCM (3 x 20 ml_) and the combined organic extracts were dried over Na2SC>4 and concentrated in vacuo. The residue was dissolved in DCM (15 ml_), treated with TFA (1.5 ml_), stirred for 2 h and concentrated in vacuo. Purification of the resulting mixture by chromatography on silica eluting with 0-100% EtOAc (+1% formic acid) in heptanes (+1% formic acid) afforded the title compound as a colourless solid. (Note: NMR analysis indicated 80% D incorporation in the ortho-position to the phenol, and 97% D incorporation in the tert- butyl group.) (0920) LC-MS (Method E): Rt 1.18 mins; (75% 215 nm) (0921) 1H NMR (500 MHz, DMSO-d6) d 12.41 (s, 1 H), 7.08 (d, J = 9.4 Hz, 0.2H), 6.92 (d, J = 11.7 Hz, 1 H), 3.77 (s, 3H), 3.55 (d, J = 1.0 Hz, 2H), 1.25 (s, 0.3H).
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