2-甲基-4-(4,4,5,5-四甲基-1,3,2-二氧硼雜環(huán)戊烷-2-基)苯胺

CAS號：590418-05-6

CAS號590418-05-6, 是硼酸硼酸酯類化合物, 分子量為233.11, 分子式C13H20BNO2, 標(biāo)準(zhǔn)純度97%, 畢得醫(yī)藥(Bidepharm)提供590418-05-6批次質(zhì)檢（如NMR, HPLC, GC）等檢測報告。

2-甲基-4-(4,4,5,5-四甲基-1,3,2-二氧硼雜環(huán)戊烷-2-基)苯胺 (請以英文為準(zhǔn),中文僅做參考)

2-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline

貨號：BD564241 2-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline 標(biāo)準(zhǔn)純度：, 97%

標(biāo)準(zhǔn)純度	包裝	價格	上海	深圳	天津	武漢	成都	VIP價格	數(shù)量

檢測信息
批次：
純度：批次查詢可見
COA MS HPLC LC-MS Microanalysis

產(chǎn)品名稱 :	2-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline
中文名稱 :	2-甲基-4-(4,4,5,5-四甲基-1,3,2-二氧硼雜環(huán)戊烷-2-基)苯胺(請以英文為準(zhǔn),中文僅做參考)
CAS號 :	590418-05-6
分子式 :	C₁₃H₂₀BNO₂
線性分子式 :	-
分子量 :	233.11
MDL NO :	MFCD09033882
沸點(diǎn) :	-
Pubchem ID :	22559200
InChIKey :	BXTJBKJWBAHLEZ-UHFFFAOYSA-N

常用 :

SDS-BD564241 MOL

2D :

3D :

【用途一】

計算化學(xué)

Physicochemical Properties

Num. heavy atoms	17
Num. arom. heavy atoms	6
Fraction Csp3	0.54
Num. rotatable bonds	1
Num. H-bond acceptors	2.0
Num. H-bond donors	1.0
Molar Refractivity	72.29
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	44.48 ?2

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	0.0
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	2.59
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	1.88
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.	1.4
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	1.61
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.5

Water Solubility

Log S (ESOL)? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-3.11
Solubility	0.18 mg/ml ; 0.000772 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-3.17
Solubility	0.157 mg/ml ; 0.000672 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	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	-4.03
Solubility	0.0217 mg/ml ; 0.0000929 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	Yes
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	No
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	No
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	Yes
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-5.88 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	2.0 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)	2.79

合成路線：*資料僅供科研用途參考，更多細(xì)節(jié)請參閱原文出處。

1. 合成：590418-05-6

583-75-5

73183-34-3

590418-05-6

產(chǎn)率

合成條件

實(shí)驗(yàn)步驟

77%

With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate In 1,4-dioxane at 85℃; for 16 h; Inert atmosphere

化合物13-2（0405）向在二惡烷中的4-溴-2-甲基苯胺（500mg，2.69mmol），KOAc（1.32g，13.4mmol）和雙（頻哪醇合）二硼（2.05mg，8.0mmol）的混合物中加入（向4mL）中加入Pd（dppf）Cl 2（110mg，0.134mmol）。在脫氣并用氮?dú)庠俪潆姾?，將混合物?5℃下回流16小時。 TLC顯示反應(yīng)完成。加入水（20mL），用乙酸乙酯（30mL×3）萃取混合物。將合并的有機(jī)層經(jīng)Na 2 SO 4干燥，過濾，濃縮并通過硅膠柱色譜（DCM）純化，得到13-2，為白色固體（485mg，收率77％）。

21%

With potassium acetate In dimethyl sulfoxide at 80℃; for 5 h; Inert atmosphere

醋酸鉀（317毫克，3.22毫摩爾），4,4,4'，4'，5,5,5'，5'-八甲基-2,2'-雙（1,3,2-二氧雜硼雜環(huán)戊烷）（300毫克）將1.118mmol）和4-溴-2-甲基 - 苯胺（200mg，1.08mmol）溶解在DMSO（3mL）中。使用氬氣將反應(yīng)混合物脫氣。加入1,1'-二 - 二苯基膦二茂鐵二氯化鈀（II）（24mg，0.03mmol），將反應(yīng)混合物在80℃加熱5小時。將反應(yīng)混合物冷卻至室溫并用乙酸乙酯（20mL）稀釋。用飽和碳酸氫鈉（20mL）和鹽水（20mL）洗滌有機(jī)層。用硫酸鈉干燥有機(jī)層，過濾并通過快速二氧化硅柱色譜（庚烷：乙酸乙酯，0-40％）純化，得到原料和產(chǎn)物的粗混合物。使用反相柱色譜法純化混合物，得到標(biāo)題化合物，為透明油狀物（50mg，21％）。ESI-MS m / z：234（M + H）+。

21%

With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate In dimethyl sulfoxide at 80℃; for 5 h; Inert atmosphere

醋酸鉀（317毫克，3.22毫摩爾），4,4,4'，4'，5,5,5'，5'-八甲基-2,2'-雙（1,3,2-二氧雜硼雜環(huán)戊烷）（300毫克）將1.18mmol）和4-溴-2-甲基 - 苯胺（200mg，1.08mmol）溶解在二甲基亞砜（3mL）中。使用氬氣將反應(yīng)混合物脫氣。加入1,1'-雙 - 二苯基膦二茂鐵二氯化鈀（II）（24mg，0.03mmol），將反應(yīng)混合物在80℃加熱5小時。將反應(yīng)混合物冷卻至室溫并用乙酸乙酯（20mL）稀釋。用飽和碳酸氫鈉（20mL）和鹽水（20mL）洗滌有機(jī)層。用硫酸鈉干燥有機(jī)層，過濾并通過快速二氧化硅柱色譜（庚烷：乙酸乙酯，0-40％）純化，得到原料和產(chǎn)物的粗混合物。使用反相柱色譜法純化混合物，得到標(biāo)題化合物，為透明油狀物（50mg，21％）。 ESI-MS m / z：234（M + H）+。

參考文獻(xiàn)：

[1] Patent: US9138427, 2015, B2. Location in patent: Page/Page column 291
[2] Patent: WO2012/104305, 2012, A1. Location in patent: Page/Page column 150
[3] Patent: EP3034078, 2016, A1. Location in patent: Paragraph 0241-0242
[4] Patent: US2005/171131, 2005, A1. Location in patent: Page/Page column 54-55
[5] Patent: US2006/25383, 2006, A1. Location in patent: Page/Page column 54
[6] Journal of Medicinal Chemistry, 2015, vol. 58, # 5, p. 2326 - 2349

2. 合成：590418-05-6

590418-04-5

590418-05-6

參考文獻(xiàn)：

[1] Patent: US2004/44258, 2004, A1. Location in patent: Page 157

產(chǎn)率	合成條件	實(shí)驗(yàn)步驟
50%	Stage #1: With sodium hydroxide In water; toluene Stage #2: at 20℃;	通用方法：步驟3-從3-氨基苯硼酸氫制備3-氨基苯硼酸頻哪醇酯（2-（3-溴苯基）-4,4,5,5-四甲基-1,3,2-二氧雜硼雜環(huán)戊烷;化合物6）實(shí)施例2的硫酸鹽溶液。將1V甲苯加入到300g 3-氨基苯硼酸硫酸氫鹽溶液（在前一實(shí)施例的第1點(diǎn)獲得并含有約202毫摩爾產(chǎn)物）中，并在攪拌下用NaOH 33％將該混合物的pH值校正到最終pH值為8.0。 1 eq。加入頻哪醇并將所得反應(yīng)混合物在室溫下保持?jǐn)嚢柚敝赁D(zhuǎn)化完成。分離有機(jī)相并在真空下蒸發(fā)至殘余物。加入1V庚烷，將得到的漿液在20-25℃攪拌下保持1小時，得到沉淀物，過濾回收，在真空（200mmHg），40℃下干燥8小時，得到36,5 g化合物6（169毫摩爾;產(chǎn)率84％）。來自二苯甲酮的總摩爾產(chǎn)率（不分離中間體化合物5）：61％
50%	With sodium hydroxide In water at 20℃;	一般步驟：步驟3由3-氨基苯硼酸硫酸氫鹽制備3-氨基苯硼酸頻哪醇酯（2-（3-溴苯基）-4,4,5,5-四甲基-1,3,2-二氧雜硼雜環(huán)戊烷;化合物6）將實(shí)施例2的甲苯溶液加入到300g 3-氨基苯硼酸硫酸氫鹽溶液（在前一實(shí)施例的第1點(diǎn)獲得并含有約202毫摩爾產(chǎn)物）中，并在攪拌下，該混合物的pH值為用NaOH 33％校正至最終pH值為8.0。 1 eq。加入頻哪醇并將所得反應(yīng)混合物在室溫下保持?jǐn)嚢柚敝赁D(zhuǎn)化完成。分離有機(jī)相并在真空下蒸發(fā)至殘余物。加入庚烷IV，將得到的漿料在20-25℃攪拌下保持1小時，得到沉淀物，過濾回收，在真空（200mmHg），40℃下干燥8小時，得到36,5 g化合物6 {169毫摩爾; 84％的收益率）。二苯甲酮的總摩爾產(chǎn)率（不分離中間體化合物5）：61％
0.992 g	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium acetate In dimethyl sulfoxide at 85℃; for 4.50 h; Inert atmosphere	一般步驟：2.1：2-氟-4-（4,4,5,5-四甲基-1,3,2-二氧雜硼雜環(huán)戊烷-2-基）苯胺5.0g（21.1mmol）的2-氟-4-碘苯胺和將5.89g（23.2mmol）雙（頻哪醇合）乙硼烷溶解在130ml DMSO中。加入6.21g（63.3mmol）的乙酸鉀，并鼓入氬氣10分鐘。加入1.21g（1.50mmol）[1,1'-雙（二苯基膦基）二茂鐵]二氯化鈀（II），與二氯甲烷（1：1）絡(luò)合，將混合物在85℃加熱4.5小時，在氬氣，然后冷卻并用500毫升水稀釋。將混合物用乙酸乙酯（3×200ml）萃取，將有機(jī)相用水洗滌，用Na 2 SO 4干燥，然后蒸發(fā)至干。通過二氧化硅色譜法（洗脫液：環(huán)己烷/乙酸乙酯90/10）純化粗產(chǎn)物。獲得3.73g白色粉末形式的產(chǎn)物。產(chǎn)率= 75percent。熔點(diǎn)：112℃.1H NMR（400MHz; CDCl3）：δ（ppm）：1.2（s; 12H）; 3.8（br s; 2H）; 6.55（t; 1H; 7 Hz）; 7.25-7.35（m; 2H）。

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