Home Cart Sign in  
Chemical Structure| 216439-76-8 Chemical Structure| 216439-76-8

Structure of 216439-76-8

Chemical Structure| 216439-76-8

*Storage: {[sel_prStorage]}

*Shipping: {[sel_prShipping]}

,{[proInfo.pro_purity]}

4.5 *For Research Use Only !

{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]} Purity: {[proInfo.pro_purity]}

Change View

Size Price VIP Price

US Stock

Global Stock

In Stock
{[ item.pr_size ]} Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}

US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days

  • {[ item.pr_size ]}

In Stock

- +

Please Login or Create an Account to: See VIP prices and availability

US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks

  • 1-2 Day Shipping
  • High Quality
  • Technical Support
Product Citations

Alternative Products

Product Details of [ 216439-76-8 ]

CAS No. :216439-76-8
Formula : C20H30BNO6
M.W : 391.27
SMILES Code : O=C(O)[C@@H](NC(OC(C)(C)C)=O)CC1=CC=C(B2OC(C)(C)C(C)(C)O2)C=C1
MDL No. :MFCD03412130
InChI Key :QEDPTINTWPOCHA-HNNXBMFYSA-N
Pubchem ID :10644158

Safety of [ 216439-76-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 216439-76-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 28
Num. arom. heavy atoms 6
Fraction Csp3 0.6
Num. rotatable bonds 8
Num. H-bond acceptors 6.0
Num. H-bond donors 2.0
Molar Refractivity 107.82
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

94.09 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

0.0
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

3.5
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

2.51
Log Po/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.

1.41
Log Po/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

1.85
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.85

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-4.1
Solubility 0.031 mg/ml ; 0.0000792 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.

-5.16
Solubility 0.00271 mg/ml ; 0.00000693 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

-4.7
Solubility 0.00774 mg/ml ; 0.0000198 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

No
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

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-6.2 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.

0.56

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

1.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<2.0
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)

3.99

Application In Synthesis of [ 216439-76-8 ]

* 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.

  • Upstream synthesis route of [ 216439-76-8 ]

[ 216439-76-8 ] Synthesis Path-Upstream   1~6

  • 1
  • [ 220587-29-1 ]
  • [ 216439-76-8 ]
YieldReaction ConditionsOperation in experiment
76% at 20℃; for 0.5 h; This ester compound 6 was prepared based on a literature procedure (Firooznia, et al, Tetrahedron Lett., 1999, 40, 213-216). Bis(pinacolato)diboron (90 g, 1.1 eq), potassium acetate (63 g, 2 eq), tricyclohexylphosphine (2.3 g, 2.5percent mol), and palladium acetate (0.72 g, 1 molpercent) were mixed in acetonitrile (950 ml) and the resulting mixture stirred at room temperature for 5 minutes. The above triflate (5) solution (190 g, 0.32 mol) was added and the resulting mixture was heated at 800C for 1 hours and cooled. HPLC showed complete consumption of the starting material. The reaction mixture was quenched with aqueous potassium bicarbonate solution (57 g in 475 ml water) and resulting mixture was stirred at room temperature for 30 minutes. The mixture was filtered through a pad of 20 μ cellulose to remove palladium black. A sample of the organic layer was concentrated and purified by column chromatography (gradient: 1 : 10 to 1 :4 ethyl acetate/hexanes) to give the ester compound 6 as a clear oil. LC-MS (ESI): MH+ = 406.2, MNH4+ = 423.2, M2H+ = 811.5, M2NH4+ = 428.5. IH NMR (CDCl3) δ 7.76 (d, J= 8.1 Hz, 2H), 7.15 (d, J= 7.6 Hz, 2H), 4.96 (d, J= 7.3 Hz, IH), 4.60 (m, IH), 3.72 (s, 3H), 3.13 (m, 2H), 1.44 (s, 9H), 1.36 (s, 12H). The above organic layer of 6 was stirred with aqueous lithium hydroxide solution (23 g in 500 ml water) at room temperature for 30 minutes. The pH of the resulting slurry was adjusted to about 10 with 6 N hydrochloric acid and filtered. The cake was washed with water (200 ml). Acetonitrile was removed from the filtrate under reduced pressure to give an aqueous slurry (950 ml, additional water was added during distillation). The slurry was filtered through a pad of 20 μ cellulose and washed with water (200 ml). The filtrate was washed with MTBE (500 ml) and rediluted with 700 ml MTBE. The mixture was acidified to pH about 4.5 with 6 N hydrochloric acid. The organic layer was washed with water (500 ml) and concentrated under reduced pressure to the titled product (7) as a brown oil (206 g, 95percent yield based on estimated purity by NMR). The crude product was used directly in the following step. LC-MS (ESI): MH+ = 392.2, MNH4+ = 409.2, M2H+ = 783.4, M2NH4+ = 800.4. 1H NMR (CDCl3) δ 7.95 (br s, IH), 7.76 (d, J= 7.8 Hz, 2H), 7.21 (d, J= 7.6 Hz, 2H), 5.03 (d, J= 7.8 Hz, IH), 4.62 (m, IH), 3.18 (m, 2H), 1.43 (s, 9H), 1.35 (s, 12H). 13C NMR (CDCl3) δ 175.8, 155.7, 139.7, 135.4, 129.2, 84.2, 80.5, 54.5, 38.3, 28.7, 25.2.Compound 7 can optionally isolated by crystallization. Thus, the above MTBE solution of 7 can be dried with anhydrous Na2SO4 and concentrated to about 1.0 vol under vacuum. Heptane (2.5 vol) was added and concentrated to about 1.5 vol under vacuum. Heptane (4.2 vol) was added slowly at 36~42°C followed by cooling slowly to 5~10°C. The resulting slurry is filtered, washed by heptane, and dried under vacuum at 20-300C to give the product 7 in about 76percent yield.
4.91g With lithium hydroxide In tetrahydrofuran; water at 20℃; for 1 h; (2S) -2- (tert-butoxycarbonylamino) -3- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl] propionate (5.21 g, a 12.9 mmol) was dissolved in tetrahydrofuran (60 mL), 4N aqueous lithium hydroxide solution (6.45 mL, and stirred for 1 hour at room temperature was added a 25.8 mmol). The reaction was diluted with saturated aqueous sodium chloride solution, and extracted with ethyl acetate. After drying the extract over anhydrous sodium sulfate combined, to give the title compound (4.91 g) under reduced pressure to concentrate.
602 mg With water; lithium hydroxide In tetrahydrofuran; methanol at 20℃; for 5 h; An aqueous solution of LiOH (216 mg, 5.04 mmol, 3 equiv) in H2O (3.30 mL) was added to a solution of Boc-Phe(4-BPin)-OMe (680 mg, 1.68 mmol, 1 equiv) in MeOH/THF (1:1, 6.60 mL).The reaction mixture was stirred at room temperature for 5 h. After this time, the organic solvents were evaporated under reduced pressure and H2O (100 mL) was added to the resulting residue. The resulting solution was adjusted to pH 5 by addition of glacial AcOH followed by extraction with EtOAc (4 × 30 mL). The organic layers were combined, washed with brine (50 mL), and dried over anhydrous magnesium sulfate. Removal of the solvent afforded Boc-Phe(4-BPin)-OH [4] as a white solid (602 mg, 92percent yield). tR = 6.43 min (98percent purity).
References: [1] Patent: WO2010/47712, 2010, A1, . Location in patent: Page/Page column 26-27.
[2] Patent: US2009/48280, 2009, A1, . Location in patent: Page/Page column 9; 12-13.
[3] Patent: US2009/99206, 2009, A1, . Location in patent: Page/Page column 6.
[4] Patent: JP2016/37467, 2016, A, . Location in patent: Paragraph 0063.
[5] Beilstein Journal of Organic Chemistry, 2019, vol. 15, p. 761 - 768.
  • 2
  • [ 220587-29-1 ]
  • [ 216439-76-8 ]
  • [ 119771-23-2 ]
YieldReaction ConditionsOperation in experiment
95 %Spectr.
Stage #1: at 20℃; for 0.5 h;
Stage #2: With hydrogenchloride In tert-butyl methyl ether; water
The above organic layer of the ester was stirred with aqueous lithium hydroxide solution (23 g in 500 mL water) at r.t. for 30 minutes. The pH of the resulting slurry was adjusted to about 10 with 6 N hydrochloric acid and filtered. The cake was washed with water (200 mL). Acetonitrile was removed from the filtrate under reduced pressure to give an aqueous slurry (950 mL, additional water was added during distillation). The slurry was filtered through a pad of 20 micron cellulose and washed with water (200 mL). The filtrate was washed with MTBE (500 mL) and rediluted with 700 mL MTBE. The mixture was acidified to pH about 4.5 with 6 N hydrochloric acid. The organic layer was washed with water (500 mL) and concentrated under reduced pressure to the acid compound as a brown oil (206 g, 95percent yield based on estimated purity by NMR). The crude product can be used directly in the following step. Alternatively, the compound can be purified by crystallization from MTBE/heptane to give a white solid, which contains a small amount of the corresponding boronic acid, (S)-3-(4-boronophenyl)-2-(tert-butoxycarbonylamino)propanoic acid. MS (ESI): MH+=392.2, MNH4+=409.2, M2H+=783.4, M2NH4+=800.4. 1H NMR (CDCl3) δ 7.95 (br s, 1H), 7.76 (d, J=7.8 Hz, 2H), 7.21 (d, J=7.6 Hz, 2H), 5.03 (d, J=7.8 Hz, 1H), 4.62 (m, 1H), 3.18 (m, 2H), 1.43 (s, 9H), 1.35 (s, 12H). 13C NMR (CDCl3) δ 175.8, 155.7, 139.7, 135.4, 129.2, 84.2, 80.5, 54.5, 38.3, 28.7, 25.2.
95 %Spectr.
Stage #1: With lithium hydroxide; water In acetonitrile at 20℃; for 0.5 h;
Stage #2: With hydrogenchloride In tert-butyl methyl ether; water
The above organic layer of the ester was stirred with aqueous lithium hydroxide solution (23 g in 500 mL water) at room temperature for 30 minutes. The pH of the resulting slurry was adjusted to about 10 with 6 N hydrochloric acid and filtered. The cake was washed with water (200 mL). Acetonitrile was removed from the filtrate under reduced pressure to give an aqueous slurry (950 mL, additional water was added during distillation). The slurry was filtered through a pad of cellulose and washed with water (200 mL). The filtrate was washed with MTBE (500 mL) and rediluted with 700 mL MTBE. The mixture was acidified to pH about 4.5 with 6 N hydrochloric acid. The organic layer was washed with water (500 mL) and concentrated under reduced pressure to the acid compound as a brown oil (206 g, 95percent yield based on estimated purity by NMR). The crude product can be used directly in the following step. Alternatively, the compound can be purified by crystallization from MTBE/heptane to give a white solid, which contains a small amount of the corresponding boronic acid, (S)-3-(4-boronophenyl)-2-(tert-butoxycarbonylamino)propanoic acid. MS (ESI): MH+=392.2, MNH4+=409.2, M2H+=783.4, M2NH4+=800.4. 1H NMR (CDCl3) δ 7.95 (br s, 1H), 7.76 (d, J=7.8 Hz, 2H), 7.21 (d, J=7.6 Hz, 2H), 5.03 (d, J=7.8 Hz, 1H), 4.62 (m, 1H), 3.18 (m, 2H), 1.43 (s, 9H), 1.35 (s, 12H). 13C NMR (CDCl3) δ 175.8, 155.7, 139.7, 135.4, 129.2, 84.2, 80.5, 54.5, 38.3, 28.7, 25.2.
References: [1] Patent: US2009/62540, 2009, A1, . Location in patent: Page/Page column 8-9.
[2] Patent: US2009/88447, 2009, A1, . Location in patent: Page/Page column 5-6.
  • 3
  • [ 76-09-5 ]
  • [ 220587-29-1 ]
  • [ 216439-76-8 ]
References: [1] Patent: US2011/124865, 2011, A1, . Location in patent: Page/Page column 4; 5.
  • 4
  • [ 103882-09-3 ]
  • [ 73183-34-3 ]
  • [ 216439-76-8 ]
References: [1] Patent: WO2013/110005, 2013, A1, . Location in patent: Paragraph 00282.
  • 5
  • [ 103882-09-3 ]
  • [ 216439-76-8 ]
References: [1] Beilstein Journal of Organic Chemistry, 2019, vol. 15, p. 761 - 768.
  • 6
  • [ 113850-76-3 ]
  • [ 73183-34-3 ]
  • [ 216439-76-8 ]
References: [1] Beilstein Journal of Organic Chemistry, 2019, vol. 15, p. 761 - 768.
 

Historical Records

Technical Information

Categories