[ CAS No. 114873-12-0 ]

Name: 114873-12-0|(R)-2-((tert-Butoxycarbonyl)amino)-3-(2,4-dichlorophenyl)propanoic acid|97%
Brand: Ambeed
SKU: A548949
Price: 12.0 USD
Availability: InStock
Rating: 92 (35 reviews)

{[proInfo.proName]} ,{[proInfo.pro_purity]}

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

2D 3D

Structure of 114873-12-0 * Storage: {[proInfo.prStorage]}

Cart0 Add to My Favorites Bulk Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

For Research Only 100K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 114873-12-0 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 114873-12-0 ]

SDS Specification

Alternatived Products of [ 114873-12-0 ]

Product Details of [ 114873-12-0 ]

CAS No. :	114873-12-0	MDL No. :	MFCD01862941
Formula :	C₁₄H₁₇Cl₂NO₄	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	-
M.W :	334.20 g/mol	Pubchem ID :	-
Synonyms :

Calculated chemistry of [ 114873-12-0 ]

Physicochemical Properties

Num. heavy atoms :	21
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.43
Num. rotatable bonds :	7
Num. H-bond acceptors :	4.0
Num. H-bond donors :	2.0
Molar Refractivity :	81.36
TPSA :	75.63 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	Yes
CYP2C9 inhibitor :	Yes
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.66 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.36
Log Po/w (XLOGP3) :	3.77
Log Po/w (WLOGP) :	3.51
Log Po/w (MLOGP) :	3.01
Log Po/w (SILICOS-IT) :	2.97
Consensus Log Po/w :	3.12

Druglikeness

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

Water Solubility

Log S (ESOL) :	-4.04
Solubility :	0.0307 mg/ml ; 0.0000919 mol/l
Class :	Moderately soluble
Log S (Ali) :	-5.05
Solubility :	0.00297 mg/ml ; 0.00000888 mol/l
Class :	Moderately soluble
Log S (SILICOS-IT) :	-4.38
Solubility :	0.014 mg/ml ; 0.0000418 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.99

Safety of [ 114873-12-0 ]

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

Application In Synthesis of [ 114873-12-0 ]

* 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 [ 114873-12-0 ]

[ 114873-12-0 ] Synthesis Path-Downstream 1~21

1
[ 114873-12-0 ]
[ 1932830-61-9 ]
[ CAS Unavailable ]

Yield	Reaction Conditions	Operation in experiment
94%	With O-benzotriazol-1-yl-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In DMF (N,N-dimethyl-formamide) at 20℃; for 18.5h;	2B Step 2B: {1-(2,4-Dichlorobenzyl)-2-[4-trans-(2-hydroxymethyl-cyclohexyl)-piperazin-1-yl]-2-oxo-ethyl}carbamic acid tert-butyl ester TRANS-4- (2-HYDROXYMETHYL-CYCLOHEXYL)-PIPERAZINE-1-CARBOXYLIC acid tert- butyl ester 3 (1.40 g, 4.7 mmol) was dissolved in dichloromethane (20 ML) and to that solution, trifluoroacetic acid (10 mL) was added. The resulting solution was stirred at room temperature for 7 h. The volatiles were removed in vacuo and the residue was then dissolved in DMF (10 mL) and treated with diisopropylethyl amine (1.80 mL, 10.3 mmol). This solution was set aside. In a separate flask, a solution containing (R) -Boc-2, 4- dichlorophenylalanine (1.73 g, 5.2 mmol) and diisopropylethyl amine (1.80 mL, 10.3 mmol) in DMF (25 mL), was treated with O-benzotriaozl-1-yl-N,N,N', N'- TETRAMETHYLURONIUM hexafluorophosphate (HBTU, 2.32 g, 6.1 MMOL). The resulting golden yellow solution was stirred at room temperature, under N2, for 30 minutes. The solution previously set aside containing the deprotected piperazine was added, and the resulting mixture was stirred for 18 h at room temperature. The reaction was diluted with EtOAc (100 mL) and washed with 0.1 N HCl and then with saturated NaHC03. The organics were washed with brine, dried over anhydrous MGS04 and filtered. The residue was purified by column chromatography, eluting with a 3: 1, then a 2: 1 v/v mixture of hexanes and EtOAc. The ester product was obtained as a light brown foam (1. 83 g, 2.2 mmol, 94 % yield based on (R) -Boc-2, 4-dichlorophenylalanine). LCMS m/z 831 (M++1). The above ester (1.75 g, 2.1 mmol) was dissolved in EtOH (5 mL) and treated with KOH (250 mg, 4.5 mmol) dissolved in H20 (1 ML). The resulting mixture was refluxed for 2 h, cooled, diluted with H20 (PH-8-9) and extracted with EtOAc. The organics were washed with brine, dried over anhydrous MGS04 and filtered. Evaporation gave the residue as an orange foam. Purification was performed by column chromatography on silica-gel, eluting with a 2: 1 v/v mixture of EtOAc and hexanes, respectively. Compound 4 was isolated as a white foam (765 mg, 1.5 mmol, 71 %). LCMS MLZ 514 (M++1).

Reference： [1]Current Patent Assignee: NEUROCRINE BIOSCIENCES INC - WO2004/58735, 2004, A2 Location in patent: Page 30

2
[ 114873-12-0 ]
[ CAS Unavailable ]
[ 932720-82-6 ]

Yield	Reaction Conditions	Operation in experiment
69.8%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 8h;	12 (i?)-2-tert-Butoxycarbonylamino-3-(2,4-dichloro-phenyl)-propinoic acid (150 mg,0.712 mmol) is dissolved in a solution of EDC (151 mg, 0.783 mmol) and HOBt (144 mg, 1.067 mmol) in 5 ml DMF, and l-(5-Chloro-2-methyl-phenyl)-piperazine (237.6 mg, 0.712 mmol) is added to the reaction mixture followed by DDPEA (459.8 mg, 3.55 mmol). A clear reaction solution is obtained and stirred at room temperature for 8 h, and the product is then extracted with ethyl acetate (25 ml). The organic layer is washed with saturated NaHCO3 and saturated NaCl solution (15 ml each), and the organic phase is then separated, dried with Na2SO4 and evaporated in vacuo resulting in [(R)-2-[4-(5-Chloro-2-methyl-phenyl)-piperazin-l-yl]-l-(2,4-dichloro-benzyl)-2-oxo-ethyl]- carbamic acid tert-butyl ester (262.4 mg, 69.8%), (m/z 528 [MH+]).

Reference： [1]Current Patent Assignee: GROB JONATHON E, MASSACHUSETTS; RADETICH; Novartis (w/o Sandoz); NOVARTIS AG; SCHULTZ (inventors); PATNAIK (inventors); DOBLE R; ZHU - WO2007/38459, 2007, A2 Location in patent: Page/Page column 70

3
(R)-2-(tert-butoxycarbonylamino)-3-(2,4-dichlorophenyl)propionic acid [ No CAS ]
[ 496-12-8 ]
[ 1346951-99-2 ]

Yield	Reaction Conditions	Operation in experiment
78%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 24h;	To a stirred solution of Boc-2,4-dichloro-d-phenylalanine (0.280 g, 0.84 mmol), EDC·HCl (0.161 g, 0.84 mmol), HOBt (0.170 g, 1.26 mmol) and DIPEA (1.12 mL, 6.29 mmol) in DMF (2.0 mL), <strong>[496-12-8]isoindoline</strong> (0. 10 g, 0.84 mmol) was added. The reaction was stirred at room temperature for 24 h. Upon completion, solvent was removed under reduced pressure and the crude was purified using column chromatography to provide desired coupled product in 78% yield. To the purified compound (0.21 g, 0.48 mmol) was added 1 M HCl (9.5 mL, 1 M in Et2O). After 4 h of stirring, the solvent was removed under reduced pressure to afford target compound 4 as a white solid. 1H NMR (400 MHz, CD3OD): delta 3.42 (d, 2H, 8.0 Hz), 4.24 (d, 1H, 12 Hz), 4.63 (t, 1H, 8.0 Hz), 4.72 (d, 1H, 16 Hz), 4.89 (d, 1H, 16 Hz), 5.00 (d, 1H, 12 Hz), 7.26 (m, 1H), 7.35 (m, 4H), 7.44 (d, 1H, 8.0 Hz), 7.54 (d, 1H, 4.0 Hz) 13C NMR (100.6 MHz, CD3OD): delta 35.3, 52.1, 53.2, 53.6, 123.7, 123.9, 128.9, 129.1, 129.2, 130.7, 132.1, 132.4, 136.0, 136.3, 136.4, 136.6, 168.1 HRMS (TOF-MS) Exact mass calcd for C17H16Cl2N2O [M+H]+: 335.0718, found: 335.0712.
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃;	General procedure: A literature procedure1 was modified by replacing triethylamine with N,N-diisopropylethylamine. To a stirred mixture of tetrahydro<strong>[496-12-8]isoindoline</strong> (0.11 mL, 1.0 mmol), N-Boc-(R)-phenylalanine (265 mg, 1.0 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (182 mg, 1.0 mmol) and anhydrous 1-hydroxybenzotriazole (203 mg, 1.5 mmol) in N,N-dimethylformamide (3.0 mL) was added N,N-diisopropylethylamine (1.3 mL, 7.5 mmol). The mixture was stirred at 20 for 16 h. The solvent was evaporated and the residue was dissolved in ethyl acetate (20 mL) and the solution was washed with water (2 x 20 mL). The combined aqueous fractions were re-extracted with ethyl acetate (2 x 20 mL) and all the combined organic layers were washed with saturated aqueous sodium hydrogen carbonate (2 x 20 mL) then with brine (20 mL) filtered and dried (MgSO4). Column chromatography (25:75 ethyl acetate: dichloromethane) of the residue gave 7c (175 mg, 48%) as a cream solid,

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 4626 - 4634
[2]Bioorganic and medicinal chemistry letters,2020

4
[ 114873-12-0 ]
[ CAS Unavailable ]
[ 1620554-46-2 ]

Yield	Reaction Conditions	Operation in experiment
88%	Stage #1: (R)-2-(tert-butoxycarbonylamino)-3-(2,4-dichlorophenyl)propionic acid With 4-methyl-morpholine; isobutyl chloroformate In tetrahydrofuran at -50℃; for 0.25h; Inert atmosphere; Stage #2: 2-(3,4-dimethoxyphenyl)-ethylamine In tetrahydrofuran at -40 - 27℃; for 2.5h;	2.a 197.4 μl of 4-methylmorpholine were added to the solution of 500 mg (1.5 mmol) of (R)-2-tert-butoxycarbonylamino-3-(2,4-dichlorophenyl)propionic acid in 10 ml of tetrahydrofuran under nitrogen, and the mixture was cooled to -50° C. After addition of 194.6 μl (1.5 mmol) of isobutyl chloroformate, the reaction solution was stirred at -50° C. for 15 min, 248.7 (1.5 mmol) of 2-(3,4-dimethoxyphenyl)ethylamine were then added, the mixture was subsequently stirred at -40° C. for a further 30 min and at room temperature for two hours. The reaction mixture was then evaporated in vacuo, the residue was taken up in 10 ml of 5% sodium hydrogencarbonate solution, and the aqueous mixture was extracted three times with 10 ml of ethyl acetate each time. Drying of the combined organic phases over sodium sulfate and stripping-off of the solvent gave 655 mg (88% yield) of tert-buty {(R)-2-(2,4-dichlorophenyl)-1-[2-(3,4-dimethoxyphenyl)ethylcarbamoyl]ethyl}carbamate as colourless crystals. LC/MS (M+Na):520.

Reference： [1]Current Patent Assignee: MERCK KGAA - US2015/361037, 2015, A1 Location in patent: Paragraph 0221; 0222

5
(R)-2-(tert-butoxycarbonylamino)-3-(2,4-dichlorophenyl)propionic acid [ No CAS ]
[ 6377-12-4 ]
C₂₆H₂₅Cl₂N₃O₃ [ No CAS ]