2-(3-氟-4-羟苯基)-7-乙烯基苯并[d]恶唑-5-醇

CAS号：524684-52-4

CAS号524684-52-4, 是Endocrinology/Hormones类化合物, 分子量为271.24, 分子式C15H10FNO3, 标准纯度98+%, 毕得医药(Bidepharm)提供524684-52-4批次质检（如NMR, HPLC, GC）等检测报告。

2-(3-氟-4-羟苯基)-7-乙烯基苯并[d]恶唑-5-醇 (请以英文为准,中文仅做参考)

2-(3-Fluoro-4-hydroxyphenyl)-7-vinylbenzo[d]oxazol-5-ol , Prinaberel

货号：BD630748 2-(3-Fluoro-4-hydroxyphenyl)-7-vinylbenzo[d]oxazol-5-ol 标准纯度：, 98+%

标准纯度	包装	价格	上海	深圳	天津	武汉	成都	VIP价格	数量

检测信息
批次：
纯度：批次查询可见
COA MS HPLC LC-MS Microanalysis

产品名称 :	2-(3-Fluoro-4-hydroxyphenyl)-7-vinylbenzo[d]oxazol-5-ol , Prinaberel
中文名称 :	2-(3-氟-4-羟苯基)-7-乙烯基苯并[d]恶唑-5-醇(请以英文为准,中文仅做参考)
CAS号 :	524684-52-4
分子式 :	C₁₅H₁₀FNO₃
线性分子式 :	-
分子量 :	271.24
MDL NO :	MFCD09954141
沸点 :	-
Pubchem ID :	656954
InChIKey :	MQIMZDXIAHJKQP-UHFFFAOYSA-N

常用 :

SDS-BD630748 MOL

2D :

3D :

【用途一】

计算化学

Physicochemical Properties

Num. heavy atoms	20
Num. arom. heavy atoms	15
Fraction Csp3	0.0
Num. rotatable bonds	2
Num. H-bond acceptors	5.0
Num. H-bond donors	2.0
Molar Refractivity	73.54
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	66.49 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.5
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	3.59
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	4.0
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	2.45
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	3.66
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	3.24

Water Solubility

Log S (ESOL)? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-4.21
Solubility	0.0169 mg/ml ; 0.0000622 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-4.67
Solubility	0.00576 mg/ml ; 0.0000212 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-5.01
Solubility	0.00267 mg/ml ; 0.00000984 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	Yes
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	Yes
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	Yes
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-5.41 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	0.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	0.0 alert
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	2.97

合成路线：*资料仅供科研用途参考，更多细节请参阅原文出处。

1~14 ►

1. 合成：524684-52-4

74-85-1

544704-73-6

524684-52-4

产率

合成条件

实验步骤

71.5%

With triethylamine In acetonitrile at 75℃; for 16 h;

例1; 2-（3-氟-4-羟基苯基）-7-乙烯基苯并恶唑-5-醇的制备向2加仑氢化器中加入2-（3-氟-4-羟基苯基）-7-溴苯并恶唑-5-醇（300g），0.926摩尔），三邻甲苯基膦（9.1克，3.3％），二乙酸钯（2.1克，1％），乙腈（4.5升）和三乙胺（375克，4当量）。用氮气和乙烯冲洗氢化器;然后将压力调节至50psi。将反应混合物加热至75℃并保持16小时，此时HPLC取样表明剩余0.2％的原料。将混合物冷却至35-40℃并通过0.2μ柱过滤，并用1,2-二乙氧基乙烷（1.2L）洗涤。将滤液真空浓缩至1.2L，加入水（1.5L）和1,2-二乙氧基乙烷（1.2L）。通过在15-20℃下添加1.4L的2N NaOH将pH调节至11-12。分离各相，并用水（300ml）和2N NaOH（20mL）萃取有机相。将合并的水相用1,2-二乙氧基乙烷（2.x.900mL）洗涤。通过在15-20℃下加入500mL 4N HCl将pH调节至2.5-3.5。保持4小时后，滤出固体并用水（3.x.200mL）洗涤。将湿滤饼悬浮在丙酮（1822mL）中并加热至54-60℃，然后保持完全溶液。在保持54-60℃的同时，在0.5小时内加入乙腈（1822mL）。通过在大气压下蒸馏至1.8-2.0L的体积浓缩溶液，然后将浓缩物冷却至45-50℃并保持0.5小时;然后冷却至-3至3℃并保持1小时。滤出固体并用预冷的乙腈（2.x.200mL）洗涤;然后在55-65℃和5-10mmHg的真空烘箱中干燥24小时，得到180g（产率71.5％）产物。将上述产物在75-80℃下溶于乙酸乙酯（23体积）中。将所得溶液冷却回25-45℃并用木炭处理。然后将滤液在大气压下浓缩至7体积，并向淤浆中加入庚烷（6体积），同时保持在75-80℃。然后将溶液冷却至45-50℃，保持0.5小时，然后冷却至0-5℃，并保持1小时。滤出固体，在55-65℃，5-10mmHg下干燥，得到87％的回收率和99.4％的纯度。

58%

With triethylamine In acetonitrile at 75℃; for 16 h;

例1; 2-（3-氟-4-羟基苯基）-7-乙烯基苯并恶唑-5-醇的制备向2加仑氢化器中加入2-（3-氟-4-羟基苯基）-7-溴苯并唑-5-醇（300g），0.926摩尔），三邻甲苯基膦（9.1克，3.3％），二乙酸钯（2.1克，1％），乙腈（4.5升）和三乙胺（375克，4当量）。用氮气和乙烯冲洗氢化器;然后将压力调节至50psi。将反应混合物加热至75℃并保持16小时，此时HPLC取样表明剩余0.2％的原料。将混合物冷却至35-40℃并通过0.2μ柱过滤，并用1,2-二乙氧基乙烷（1.2L）洗涤。将滤液真空浓缩至1.2L，加入水（1.5L）和1,2-二乙氧基乙烷（1.2L）。通过在15-20℃下添加1.4L的2N NaOH将pH调节至11-12。分离各相，并用水（300ml）和2N NaOH（20mL）萃取有机相。将合并的水相用1,2-二乙氧基乙烷（2.x.900mL）洗涤。通过在15-20℃下加入500mL 4N HCl将pH调节至2.5-3.5。保持4小时后，滤出固体并用水（3.x.200mL）洗涤。然后如下所述将产物从乙醇：水溶液中重结晶两次。将湿滤饼悬浮在乙醇（1055mL）中并加热至74-80℃。同时保持在74-80℃，加入水（422mL）。将溶液冷却至45-55℃并保持0.5小时，然后冷却至0-8℃并保持1小时。滤出固体并用预冷的乙醇：水（2：1）（2.x.200mL）溶液洗涤。然后将湿滤饼悬浮在乙醇（945mL）中并加热至74-80℃。同时保持在74-80℃，加入水（472mL）。将溶液冷却至45-55℃并保持0.5小时，然后冷却至0-8℃并保持1小时。滤出固体并用预冷的乙醇：水（2：1）（2.x.200mL）溶液洗涤。将产物在55-65℃和5-10mmHg的真空烘箱中干燥24小时，得到146g 2-（3-氟-4-羟基苯基）-7-乙烯基苯并恶唑-5-醇（58％）让）。

参考文献：

[1] Patent: US2006/199967, 2006, A1. Location in patent: Page/Page column 5-6
[2] Patent: US2006/199852, 2006, A1. Location in patent: Page/Page column 6

2. 合成：524684-52-4

7486-35-3

544704-73-6

524684-52-4

产率

合成条件

实验步骤

72%

at 115℃; for 48 h;

将二氯双（三 - 噻吩基膦）钯（II）（0.87g，1.1mmol）加入到7-溴-2-（3-氟-4-羟基苯基）-1,3-苯并恶唑-5-醇的混合物中（7.16） g，22.1mmol），三丁基（乙烯基）锡（10.5g，33.25mmol）和乙二醇二乙醚（65mL）。将反应混合物在115℃下搅拌48小时，冷却至室温并用活性炭处理。将反应混合物通过MgSO 4过滤并浓缩。通过快速色谱法在酸性硅胶（己烷/ EtOAc / CH 2 Cl 2 1/1/1）上纯化，得到白色固体（4.35g，72％收率，m.p.250-252℃）; MS m / e 272（M + H）+。分析：C 15 H 10 FNO 3计算值：C，66.42; H，3.72; N，5.16实测值：C，66.03; H，3.68; N，5.09

参考文献：

[1] Journal of Medicinal Chemistry, 2004, vol. 47, # 21, p. 5021 - 5040
[2] Patent: US2006/46968, 2006, A1. Location in patent: Page/Page column 29-30

3. 合成：524684-52-4

544704-81-6

524684-52-4

产率

合成条件

实验步骤

81%

With hydrogen fluoride In tetrahydrofuran; water; acetonitrile at 65℃; for 8 h;

将氢氟酸（48重量％，在水中，1mL）加入到5 - {[叔丁基（二甲基）甲硅烷基]氧基} -2-（4 - {[叔丁基（二甲基）甲硅烷基]氧基的溶液中 } -3-氟苯基）-7-乙烯基-1,3-苯并恶唑（1.5g，3.0mmol），THF（6mL）和乙腈（3mL）。将反应混合物在65℃下搅拌8小时，然后倒入水中。滤出沉淀的固体并干燥。从丙酮/乙醚中结晶产物，得到白色固体（0.72g，收率81％，熔点249-251℃）; MS m / e 272（M + H）+。分析：C 15 H 10 FNO 3计算值：C，66.42; H，3.72; N，5.16实测值：C，66.31; H，3.85; N，4.96

参考文献：

[1] Patent: US2006/46968, 2006, A1. Location in patent: Page/Page column 29

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合成路线

1. 合成：524684-52-4

74-85-1

544704-73-6

524684-52-4

产率

合成条件

实验参考步骤

71.5%

With triethylamine In acetonitrile at 75℃; for 16 h;

58%

With triethylamine In acetonitrile at 75℃; for 16 h;

参考文献：

[1] Patent: US2006/199967, 2006, A1. Location in patent: Page/Page column 5-6
[2] Patent: US2006/199852, 2006, A1. Location in patent: Page/Page column 6

2. 合成：524684-52-4

7486-35-3

544704-73-6

524684-52-4

产率

合成条件

实验参考步骤

72%

at 115℃; for 48 h;

参考文献：

[1] Journal of Medicinal Chemistry, 2004, vol. 47, # 21, p. 5021 - 5040
[2] Patent: US2006/46968, 2006, A1. Location in patent: Page/Page column 29-30

3. 合成：524684-52-4

544704-81-6

524684-52-4

产率

合成条件

实验参考步骤

81%

With hydrogen fluoride In tetrahydrofuran; water; acetonitrile at 65℃; for 8 h;

参考文献：

[1] Patent: US2006/46968, 2006, A1. Location in patent: Page/Page column 29

4. 合成：524684-52-4

544704-84-9

524684-52-4

产率

合成条件

实验参考步骤

46%

Stage #1: With potassium carbonate In 1,4-dioxane at 90℃; for 1 h;
Stage #2: With hydrogenchloride In 1,4-dioxane; water

将碳酸钾（55mg）加入到2- [4-（乙酰氧基）-3-氟苯基] -7-乙烯基-1,3-苯并恶唑-5-基乙酸酯（0.14g，0.39mmol）和1的溶液中， 4-二恶烷（3mL）。将反应混合物在90℃下搅拌1小时，倒入水中，用HCl（2N）酸化并用EtOAc萃取。用MgSO 4干燥有机萃取物。蒸发并从EtOAc /己烷中结晶，得到白色固体（0.06g，46％收率，m.p.250-252℃）; MS m / e 272（M + H）+。分析：C 15 H 10 FNO 3计算值：C，66.42; H，3.72; N，5.16实测值：C，66.32; H，3.47; N，5.18

参考文献：

[1] Patent: US2006/46968, 2006, A1. Location in patent: Page/Page column 30

5. 合成：524684-52-4

629-14-1

7486-35-3

544704-73-6

524684-52-4

参考文献：

[1] Patent: US2003/199562, 2003, A1

6. 合成：524684-52-4

123-91-1

544704-84-9

524684-52-4

参考文献：

[1] Patent: US2003/199562, 2003, A1

7. 合成：524684-52-4