906673-24-3

Basic information

• Product Name: 5-(4-cyanophenoxy)-2,3-dihydro-1-hydroxy-2,1-benzoxaborole
• Synonyms: 4-[(1,3-Dihydro-1-hydroxy-2,1-benzoxaborol-5-yl)oxy]benzonitrile AN 2728;AN-2728, >=98%;AN2728, Crisaborole;Crisaborole (AN2728);5-(4-cyanophenoxy)-2,3-dihydro-1-hydroxy-2,1-benzoxaborole;AN 2728;AN2728/AN-2728;4-((1-Hydroxy-1,3-dihydrobenzo-[c][1,2]oxaborol-5-yl)oxy)benzonitrile
• CAS NO: 906673-24-3
• Molecular Formula: C₁₄H₁₀BNO₃
• Molecular Weight: 251
• Mol File: 906673-24-3.mol
• Article Data: 28

Chemical Properties

• Boiling Point: 425.9±55.0 °C(Predicted)
• Appearance: /
• Density: 1.33±0.1 g/cm3(Predicted)
• Storage Temp.: room temp
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 7.00±0.20(Predicted)
• CAS DataBase Reference: 5-(4-cyanophenoxy)-2,3-dihydro-1-hydroxy-2,1-benzoxaborole(CAS DataBase Reference)
• NIST Chemistry Reference: 5-(4-cyanophenoxy)-2,3-dihydro-1-hydroxy-2,1-benzoxaborole(906673-24-3)
• EPA Substance Registry System: 5-(4-cyanophenoxy)-2,3-dihydro-1-hydroxy-2,1-benzoxaborole(906673-24-3)

Safety Data

• Hazardous Substances Data: 906673-24-3(Hazardous Substances Data)

Usage

Description

Different sources of media describe the Description of 906673-24-3 differently. You can refer to the following data:
1. Crisaborole is a phosphodiesterase- 4 (PDE4) inhibitor that was approved by the USFDA for the treatment of mild to moderate atopic dermatitis (AD) in patients aged two years and older. The drug, which was developed by Anacor Pharmaceuticals and later acquired and marketed by Pfizer, is delivered as a 2% ointment, which is applied topically. The unique employment of boron within the chemical structure of the drug is designed to enable selective engagement of PDE4 (an enzyme involved in the conversion of cAMP into AMP, which signals for downstream inflammatory events), effective penetration of the drug through human skin, and rapid clearance to limit systemic circulation.
2. AN2728 is a boron-based, topical anti-inflammatory agent that inhibits phosphodiesterase 4 (PDE4; IC50 = 0.11 μM). It is less potent against PDE1A, PDE3A, and PDE7A (IC50s = 6.12, 6.41, and 0.73 μM, respectively). AN2728 suppresses the release of the proinflammatory cytokines TNF-α, IL-2, INF-γ, IL-5, and IL-10 with IC50 values of 0.50, 0.59, 0.72, 2.25, and 2.58 μM, respectively.

Uses

A series of phenoxy benzoxaboroles were synthesized and screened for their inhibitory activity against PDE4 and cytokine release. 5-?(4-?Cyanophenoxy)?-?2,?3-?dihydro-?1-?hydroxy-?2,?1-?benzoxaborole (AN2728) showed potent activity both in vitro and in vivo. AN2728 is being studied as an anti-inflammatory agent.

Biochem/physiol Actions

Crisaborole is a non-steroidal anti-inflammatory phosphodiesterase 4 (PDE4) inhibitor. Crisaborole has an IC50 value of 490 nM for PDE4 with similar IC50 values for release of cytokines TNF-α, IL-2, and IFN-γ, and shows little inhibition against other PDE isozymes. Crisaborole has been approved as a topical treatment for atopic dermatitis.

Synthesis

Several disclosures describing synthetic approaches to ethereal boron-containing anti-inflammatory compounds have been published by Anacor. Commercially available bromobenzaldehyde 134 was protected as the corresponding acetal upon subjection to warm ethylene glycol in the presence of catalytic p-toluenesulfonic acid. This was followed by nucleophilic aromatic substitution involving 4-fluorobenzonitrile and subsequent acetal deprotection to furnish diaryl ether 136. Although multiple approaches to crisaborole have been reported from this intermediate diaryl ether 136, the published literature approach involves the following sequence: reduction of the aldehyde with sodium borohydride followed by THP protection to furnish bromobenzene 137, which then underwent lithium-halogen exchange prior to quenching with triisopropyl borate and acidification to arrive at crisaborole (XIII). Alternatively, patents from Anacor describe a general approach employing a Miyaura coupling of 136, enabling the installation of the corresponding pincacol borane, which could then be exposed to reduction conditions using sodium borohydride followed by boric acid wash, aqueous workup, and lyophilization to furnish XIII.

Synthetic route

4-Cyanochlorobenzene (623-03-0) + 1,3-dihydro-1,5-dihydroxy-2,1-benzoxaborolane (1187190-70-0) → AN2728 (906673-24-3)

Conditions	Yield
With caesium carbonate In dimethyl sulfoxide at 60℃; Reagent/catalyst; Temperature; Solvent;	95%

1,3-dihydro-1,5-dihydroxy-2,1-benzoxaborolane (1187190-70-0) + 4-fluorobenzonitrile (1194-02-1) → AN2728 (906673-24-3)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 110℃; for 12h; Reagent/catalyst; Temperature;	95%
With potassium carbonate In dimethyl sulfoxide at 60 - 70℃; for 4h; Reagent/catalyst; Temperature; Solvent; Inert atmosphere;	76.9%

1,3-dihydro-1,5-dihydroxy-2,1-benzoxaborolane (1187190-70-0) + 4-bromobenzenecarbonitrile (623-00-7) → AN2728 (906673-24-3)

Conditions	Yield
With caesium carbonate In dimethyl sulfoxide at 60℃; Reagent/catalyst; Solvent; Temperature;	93.3%

5-(4-cyanophenoxy)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetate → AN2728 (906673-24-3)

Conditions	Yield
With hydrogenchloride In tetrahydrofuran; water at 40℃; Reagent/catalyst; Solvent; Temperature;	93%
With sodium hydroxide at 15 - 45℃;	91%

4-(3-(hydroxymethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)benzonitrile → AN2728 (906673-24-3)

Conditions	Yield
With hydrogenchloride In water at 80℃; for 4h;	93%

C25H30BNO5 → AN2728 (906673-24-3)

Conditions	Yield
With methanesulfonic acid In ethanol; water at 20 - 30℃; for 24h; Solvent; Reagent/catalyst;	92%

2,6-dichloro-4-((1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-5-yl)oxy)benzonitrile → AN2728 (906673-24-3)

Conditions	Yield
With 5%-palladium/activated carbon; hydrogen; potassium hydroxide In ethanol; water under 760.051 - 3800.26 Torr; for 1h;	90%

pinacol 4-(4-cyanophenoxy)-2-bromomethylphenylborate → AN2728 (906673-24-3)

Conditions	Yield
With water; potassium hydroxide at 55 - 65℃; for 2h; Inert atmosphere;	90%

4-(3-formyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)benzonitrile + water (7732-18-5) → AN2728 (906673-24-3)

Conditions	Yield
Stage #1: 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-formylphenoxy]benzonitrile With sodium tetrahydroborate; ethanol at 0 - 5℃; for 1h; Inert atmosphere; Stage #2: water With hydrogenchloride at 40 - 45℃; for 0.5h; Inert atmosphere;	89.4%
Stage #1: 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-formylphenoxy]benzonitrile With methanol; sodium tetrahydroborate at 0 - 15℃; for 1h; Inert atmosphere; Stage #2: water With hydrogenchloride pH=4 - 6; Temperature;	76.5%

C26H36BNO4Si → AN2728 (906673-24-3)

Conditions	Yield
With hydrogenchloride In tetrahydrofuran; water at 40℃; for 5h;	87%

C26H36BNO4Si → AN2728 (906673-24-3)

Conditions	Yield
With hydrogenchloride In tetrahydrofuran; water at 40℃; for 5h;	87%

diisobutyl 4-(4-cyanophenoxy)-2-bromomethylbenzeneborate → AN2728 (906673-24-3)

Conditions	Yield
With water; potassium hydroxide at 40 - 50℃; for 6h; Inert atmosphere;	85%

4-(4-cyanophenoxy)-2-chloromethylbenzeneboronic acid → AN2728 (906673-24-3)

Conditions	Yield
With triethylamine In water at 50 - 60℃; for 10h; Inert atmosphere;	84%

Triisopropyl borate (5419-55-6) + [5-(4-nitrylphenoxy)-2-bromophenyl-1-methoxy]trimethylsilane + water (7732-18-5) → AN2728 (906673-24-3)

Conditions	Yield
Stage #1: Triisopropyl borate; [5-(4-nitrylphenoxy)-2-bromophenyl-1-methoxy]trimethylsilane With n-hexyllithium In tetrahydrofuran; hexane at -78 - 20℃; Inert atmosphere; Stage #2: water With hydrogenchloride In tetrahydrofuran; hexane pH=1 - 2; Inert atmosphere;	82%

4-(4-cyanophenoxy)-2-formylbenzeneboronic acid → AN2728 (906673-24-3)

Conditions	Yield
With sodium tetrahydroborate In methanol at 4℃; for 25h;	81%

pinacol 4-(4-cyanophenoxy)-2-methylphenylborate → AN2728 (906673-24-3)

Conditions	Yield
Stage #1: pinacol 4-(4-cyanophenoxy)-2-methylphenylborate With 5,5-dibromohydantoin In chlorobenzene at 75℃; for 2h; Stage #2: With water; sodium hydroxide In chlorobenzene at 45℃; for 1h;	80.9%

tetrahydroxydiboron (13675-18-8) + 4-(4-bromo-3-(hydroxymethyl)phenoxy)benzonitrile (906673-45-8) → AN2728 (906673-24-3)

Conditions	Yield
With (chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II)); potassium acetate; ethylene glycol; XPhos In methanol at 64 - 66℃; Reagent/catalyst; Inert atmosphere; Sealed tube;	80%

tetrahydroxydiboron (13675-18-8) + 4-(4-amino-3-(hydroxymethyl)phenoxy)benzonitrile → AN2728 (906673-24-3)

Conditions	Yield
Stage #1: 4-(4-amino-3-(hydroxymethyl)phenoxy)benzonitrile With hydrogenchloride; sodium nitrite In methanol; water at 0℃; for 0.5h; Stage #2: tetrahydroxydiboron In methanol; water for 1h;	75%

2-methoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1195-66-0) + [5-(4-nitrylphenoxy)-2-bromophenyl-1-methoxy]trimethylsilane → AN2728 (906673-24-3)

Conditions	Yield
Stage #1: [5-(4-nitrylphenoxy)-2-bromophenyl-1-methoxy]trimethylsilane With isopropylmagnesium chloride In tetrahydrofuran at -20 - 20℃; for 3h; Inert atmosphere; Stage #2: 2-methoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane In tetrahydrofuran at 0 - 25℃; for 8h; Inert atmosphere;	72%

C25H32BNO5 → AN2728 (906673-24-3)

Conditions	Yield
With hydrogenchloride; water In tetrahydrofuran at 20℃; for 3h;
With hydrogenchloride In methanol at 20 - 30℃; for 24h;

Reaxys ID: 32488018 → AN2728 (906673-24-3)

4-(4-bromo-3-(hydroxymethyl)phenoxy)benzonitrile (906673-45-8) + Trimethyl borate (121-43-7) → AN2728 (906673-24-3)

Conditions	Yield
With n-butyllithium In tetrahydrofuran at -78℃;	Ca. 17 g

4-(4-bromo-3-(hydroxymethyl)phenoxy)benzonitrile (906673-45-8) + Triisopropyl borate (5419-55-6) → AN2728 (906673-24-3)

Conditions	Yield
With n-butyllithium In tetrahydrofuran at -78℃;	Ca. 1.8 g

4-(4-bromo-3-(hydroxymethyl)phenoxy)benzonitrile (906673-45-8) → AN2728 (906673-24-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: dmap / tetrahydrofuran / 1 h / 20 °C 2: potassium acetate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane / 4 h / 85 °C / Inert atmosphere 3: hydrogenchloride / tetrahydrofuran; water / 40 °C View Scheme
Multi-step reaction with 3 steps 1: pyridine / dichloromethane / 20 °C 2: potassium carbonate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane / 4 h / 80 °C / Inert atmosphere 3: sodium hydroxide / 15 - 45 °C View Scheme
Multi-step reaction with 4 steps 1: pyridine / dichloromethane / 20 °C 2: potassium carbonate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane / 4 h / 80 °C / Inert atmosphere 3: sodium hydroxide; methanol / 20 °C 4: hydrogenchloride / water / 4 h / 80 °C View Scheme

4-(3-(hydroxymethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)benzonitrile + water (7732-18-5) → AN2728 (906673-24-3)

Conditions	Yield
With hydrogenchloride at 0℃;	0.4 g

4-(4-bromo-3-formaldehydephenoxy)benzonitrile (906673-54-9) → AN2728 (906673-24-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydroxide; water; sodium tetrahydroborate / methanol / 1 h / 0 °C / Inert atmosphere 2: potassium acetate; XPhos; (chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II)); ethylene glycol / methanol / 64 - 66 °C / Inert atmosphere; Sealed tube View Scheme
Multi-step reaction with 3 steps 1: potassium acetate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 2-methyltetrahydrofuran / 2 h / 80 °C / Inert atmosphere 2: methanol; sodium tetrahydroborate / 0.5 h / 0 - 20 °C 3: hydrogenchloride / 0 °C View Scheme
Multi-step reaction with 4 steps 1: sodium tetrahydroborate; methanol / 10 - 30 °C 2: pyridine / dichloromethane / 20 °C 3: potassium carbonate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane / 4 h / 80 °C / Inert atmosphere 4: sodium hydroxide / 15 - 45 °C View Scheme

2-bromo-5-hydroxybenzaldehyde (2973-80-0) → AN2728 (906673-24-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium carbonate / N,N-dimethyl-formamide; toluene / 8 h / 115 °C / Inert atmosphere 2: sodium hydroxide; water; sodium tetrahydroborate / methanol / 1 h / 0 °C / Inert atmosphere 3: potassium acetate; XPhos; (chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II)); ethylene glycol / methanol / 64 - 66 °C / Inert atmosphere; Sealed tube View Scheme
Multi-step reaction with 4 steps 1: potassium carbonate / N,N-dimethyl-formamide; toluene / 8 h / 115 °C / Inert atmosphere 2: potassium acetate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 2-methyltetrahydrofuran / 2 h / 80 °C / Inert atmosphere 3: methanol; sodium tetrahydroborate / 0.5 h / 0 - 20 °C 4: hydrogenchloride / 0 °C View Scheme
Multi-step reaction with 3 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 20 h / 75 - 85 °C 2.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 8 h / 65 - 70 °C 3.1: sodium tetrahydroborate; methanol / 1 h / 0 - 15 °C / Inert atmosphere 3.2: pH 4 - 6 View Scheme

4-fluorobenzonitrile (1194-02-1) → AN2728 (906673-24-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium carbonate / N,N-dimethyl-formamide; toluene / 8 h / 115 °C / Inert atmosphere 2: sodium hydroxide; water; sodium tetrahydroborate / methanol / 1 h / 0 °C / Inert atmosphere 3: potassium acetate; XPhos; (chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II)); ethylene glycol / methanol / 64 - 66 °C / Inert atmosphere; Sealed tube View Scheme
Multi-step reaction with 4 steps 1: potassium carbonate / N,N-dimethyl-formamide; toluene / 8 h / 115 °C / Inert atmosphere 2: potassium acetate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 2-methyltetrahydrofuran / 2 h / 80 °C / Inert atmosphere 3: methanol; sodium tetrahydroborate / 0.5 h / 0 - 20 °C 4: hydrogenchloride / 0 °C View Scheme
Multi-step reaction with 3 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 20 h / 75 - 85 °C 2.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 8 h / 65 - 70 °C 3.1: sodium tetrahydroborate; methanol / 1 h / 0 - 15 °C / Inert atmosphere 3.2: pH 4 - 6 View Scheme
Multi-step reaction with 4 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 80 - 90 °C 2.1: toluene-4-sulfonic acid / dichloromethane / 20 °C 3.1: n-butyllithium / tetrahydrofuran; hexane / 1 h / -75 - 80 °C / Inert atmosphere 3.2: -75 - 80 °C 4.1: hydrogenchloride / methanol / 24 h / 20 - 30 °C View Scheme
Multi-step reaction with 4 steps 1: potassium carbonate / N,N-dimethyl-formamide / 80 - 90 °C 2: toluene-4-sulfonic acid / dichloromethane / 20 °C 3: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 20 h / 90 - 100 °C / Autoclave; Inert atmosphere 4: methanesulfonic acid / ethanol; water / 24 h / 20 - 30 °C View Scheme

4-cyanophenol (767-00-0) → AN2728 (906673-24-3)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: sodium hydroxide / water; 1,4-dioxane / 0.5 h / 20 °C 1.2: 3 h / 55 °C 2.1: hydrogenchloride / 1 h / 20 °C 3.1: sodium tetrahydroborate / tetrahydrofuran 4.1: sodium nitrite; hydrogenchloride / methanol; water / 0.5 h / 0 °C 4.2: 1 h View Scheme
Multi-step reaction with 4 steps 1.1: sodium hydroxide / water; 1,4-dioxane / 0.5 h / 20 °C 1.2: 3 h / 55 °C 2.1: hydrogenchloride / 1 h / 20 °C 3.1: sodium tetrahydroborate / tetrahydrofuran 4.1: sodium nitrite; hydrogenchloride / methanol; water / 0.5 h / 0 °C 4.2: 1 h View Scheme
Multi-step reaction with 6 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 12 h / 95 - 100 °C 2.1: potassium carbonate / methanol; water / 1 h / 40 °C 3.1: 1H-imidazole / dichloromethane / 3 h / 25 °C 4.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 1 h 4.2: 20 - 30 °C 5.1: cesium acetate; pyridine / ethyl acetate / 20 h / 30 - 35 °C / Inert atmosphere; Irradiation 6.1: hydrogenchloride / water; tetrahydrofuran / 5 h / 40 °C View Scheme
Multi-step reaction with 6 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 12 h / 95 - 100 °C 2.1: potassium carbonate / methanol; water / 1 h / 40 °C 3.1: 1H-imidazole / acetone / 4 h / 30 - 40 °C 4.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / tetrahydrofuran / 1 h 4.2: 5 h / 20 - 30 °C 5.1: cesium acetate; picoline / ethyl acetate / 16 h / 30 - 35 °C / Inert atmosphere; Irradiation 6.1: hydrogenchloride / water; tetrahydrofuran / 5 h / 40 °C View Scheme

AN2728 (906673-24-3) → 4-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-5-yloxy)benzoic acid

Conditions	Yield
With sodium hydroxide; water In 1,4-dioxane; methanol for 144h; Reflux;	79%
With sodium hydroxide In ethanol for 3h; Heating / reflux;	8%
Stage #1: AN2728 With sodium hydroxide In ethanol for 3h; Heating / reflux; Stage #2: With hydrogenchloride Product distribution / selectivity;	8%
With water; sodium hydroxide In ethanol for 3h; Solvent; Temperature; Time; Reflux;	8%
Stage #1: AN2728 With sodium hydroxide In ethanol; water for 3h; Heating / reflux; Stage #2: With hydrogenchloride In ethanol; water	8%

AN2728 (906673-24-3) + butyric acid (107-92-6) → C18H16BNO4

Conditions	Yield
Stage #1: butyric acid With 1,1'-carbonyldiimidazole In tetrahydrofuran at 60℃; for 1h; Stage #2: AN2728 In tetrahydrofuran for 2h;	76.32%

AN2728 (906673-24-3) + dimethylphosphoric acid (813-78-5) → C16H15BNO6P

Conditions	Yield
Stage #1: dimethylphosphoric acid With 1,1'-carbonyldiimidazole In tetrahydrofuran at 60℃; for 1h; Stage #2: AN2728 In tetrahydrofuran for 2h;	66.58%

AN2728 (906673-24-3) + isobutyric Acid (79-31-2) → C18H16BNO4

Conditions	Yield
Stage #1: isobutyric Acid With 1,1'-carbonyldiimidazole In tetrahydrofuran at 60℃; for 1h; Stage #2: AN2728 In tetrahydrofuran for 2h;	62.46%

AN2728 (906673-24-3) + 3-Phenylpropionic acid (501-52-0) → C23H18BNO4

Conditions	Yield
Stage #1: 3-Phenylpropionic acid With 1,1'-carbonyldiimidazole In tetrahydrofuran at 60℃; for 1h; Stage #2: AN2728 In tetrahydrofuran for 2h;	62.06%

AN2728 (906673-24-3) + diphenyl hydrogen phosphate (838-85-7) → C26H19BNO6P

Conditions	Yield
Stage #1: diphenyl hydrogen phosphate With 1,1'-carbonyldiimidazole In tetrahydrofuran at 60℃; for 1h; Stage #2: AN2728 In tetrahydrofuran for 2h;	43.38%

AN2728 (906673-24-3) → 5-(4-(1H-tetrazol-5-yl)phenoxy)benzo[c][1,2]oxaborol-1(3H)-ol (947162-19-8)

Conditions	Yield
With sodium azide; ammonium chloride In N,N-dimethyl-formamide at 80℃; for 48h;	23%

AN2728 (906673-24-3) → 1-hydroxy-5-[4-(tetrazole-1-yl)phenoxy]-2,1-benzoxaborole

Conditions	Yield
With sodium azide; ammonium chloride In N,N-dimethyl-formamide at 80℃; for 48h;	23%
With sodium azide; ammonium chloride In N,N-dimethyl-formamide at 80℃; for 48h;	23%
With sodium azide; ammonium chloride In N,N-dimethyl-formamide at 80℃; for 48h;	23%

AN2728 (906673-24-3) → 4-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-5-yloxy)benzamide

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydroxide; water / ethanol / 3 h / Reflux 2: 1,1'-carbonyldiimidazole; ammonium bicarbonate / N,N-dimethyl-formamide / 20 °C View Scheme

Upstream product

• 7732-18-5 water 
• 7070-85-1 3-[1,3]dioxolan-2-yl-phenol 
• 100-83-4 meta-hydroxybenzaldehyde 
• 99-06-9 3-Carboxyphenol 
• 7781-98-8 ethyl-3-hydroxybenzoate 
• 620-24-6 3-Hydroxybenzyl alcohol 
• 906673-48-1 2-bromo-5-tert-butyldimethylsiloxybenzylalcohol 
• 351418-50-3 2-bromo-5-(tert-butyldimethylsilanyloxy)benzaldehyde 
• 64169-34-2 5-bromophthalide 

Downstream Products

• 1187187-13-8 4-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-5-yloxy)benzoic acid methyl ester 
• 947162-19-8 5-(4-(1H-tetrazol-5-yl)phenoxy)benzo[c][1,2]oxaborol-1(3H)-ol 

Relevant articles and documents

Preparation method of benzoxaborole compound

The invention discloses a preparation method of a benzoxaborole compound. The preparation method comprises the following steps: (1) reacting raw materials containing halogenated hydrocarbon and boric acid ester under an alkaline condition, acidifying and hydrolyzing to obtain an intermediate VI; and (2) reacting a raw material containing the intermediate VI with halogenated cyanophenyl to obtain the benzoxaborole compound. The raw materials are low in price, the preparation cost of the benzoxaborole compound is reduced, the steps of protection and de-protection of organic groups are not needed in the preparation process, the reaction process is simplified, and yield reduction caused by group protection is avoided; and meanwhile, the method is mild in reaction condition, low in equipment requirement and easy for large-scale industrial production.

Crisaborole intermediate, preparation method and application of crisaborole intermediate in preparation of crisaborole

The invention discloses a crisaborole intermediate, a preparation method and application of the crisaborole intermediate in preparation of crisaborole. The crisaborole intermediate has a structure asshown in a formula I in the specification. The preparation method comprises the following steps: carrying out Grignard reaction on a compound shown in a structural formula VI in an organic solvent A or carrying out exchange reaction with a metal Grignard reagent, and reacting with borate to obtain a compound shown in a structural formula V; reacting the obtained compound with the structural formula V with pinacol in an organic solvent B to obtain a compound with a structural formula IV; removing a protecting group from the compound shown in the structural formula IV in an organic solvent C toobtain a compound shown in a structural formula III; and carrying out a coupling reaction on the compound shown in the structural formula III and 4-halogenated cyanophenyl shown in the structural formula II in an organic solvent D under an alkaline condition to obtain the crisaborole intermediate shown in the structural formula I. The method effectively solves the problems of high production costand low product purity, and is suitable for industrial large-scale production.

METHOD FOR PREPARING CRISABOROLE

The invention relates to a method for preparing Crisaborole of Formula I, comprising using m-methylphenol as the starting material to obtain a target product through a five-step reaction. The starting materials and the raw materials used in each step of the method according to the present invention are cheap and easy to obtain, and the process is simple. The reaction of introducing boron atoms into the benzene ring to form an oxygen boron heterocycle is novel, with high yield and mild conditions, and is suitable for industrial production.