473838-66-3|Benzyl 3,3-dimethyl-4-oxopiperidine-1-carboxylate| Ambeed

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

Quality Control of [ 473838-66-3 ] Purity: 97% SDS Specification

COA

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

NMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

CNMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

HPLC

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

LC-MS

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

1-2 Day Shipping
High Quality
Technical Support

Product Details of [ 473838-66-3 ]

CAS No. :	473838-66-3
Formula :	C₁₅H₁₉NO₃
M.W :	261.32
SMILES Code :	O=C(N1CC(C)(C)C(CC1)=O)OCC2=CC=CC=C2
MDL No. :	MFCD11044473
InChI Key :	QHCSLEQTUOGKAJ-UHFFFAOYSA-N
Pubchem ID :	22278861

Safety of [ 473838-66-3 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302
Precautionary Statements:	P280-P305+P351+P338

Computational Chemistry of [ 473838-66-3 ] Show Less

Physicochemical Properties

Num. heavy atoms	19
Num. arom. heavy atoms	6
Fraction Csp3	0.47
Num. rotatable bonds	4
Num. H-bond acceptors	3.0
Num. H-bond donors	0.0
Molar Refractivity	76.17
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	46.61 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.83
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	2.01
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.09
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.	1.85
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	2.52
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.26

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.7
Solubility	0.526 mg/ml ; 0.00201 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.	-2.62
Solubility	0.633 mg/ml ; 0.00242 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	-3.87
Solubility	0.0353 mg/ml ; 0.000135 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	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	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	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.	-6.47 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: 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<0.0
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)	2.25

Application In Synthesis of [ 473838-66-3 ]

* 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 [ 473838-66-3 ]

[ 473838-66-3 ] Synthesis Path-Downstream 1~35

1
[ 473838-66-3 ]
[ 473838-67-4 ]

Yield	Reaction Conditions	Operation in experiment
225 g (77%)	With ammonium acetate; sodium cyanoborohydride; In hydrogenchloride; methanol; water;	Step-2 4-Amino-1-benzyloxycarbonyl-3,3-dimethylpiperidine <strong>[473838-66-3]1-Benzyloxycarbonyl-3,3-dimethyl-4-piperidone</strong> (290 g, 1.11 mol) was dissolved in methanol (1.5 L) and under stirring addition of ammonium acetate (600 g, 7.80 mol) was made at 30-35 C. The reaction mixture was stirred for 5 hrs. Sodium cyanoborohydride (35 g, 0.55 mol) was added portion wise to the suspension over 0.5 hrs by maintaining temperature between 0-10 C. The reaction mixture was stirred for 6-7 hrs. After completion of reaction, solvent was evaporated under reduced pressure and addition of 3.00 L water was made under stirring. The reaction mixture was stirred for 15 minutes. It was extracted with 1.5 L2 CHCl3. Combined organic extract was evaporated under vacuum. The residue was dissolved in 3 N HCl till pH 1 and was extracted with 500 ml2 dichloromethane. The aqueous layer was basified with 300 ml aqueous ammonia solution (23-25%) to pH 10-11 and then was extracted with 1.5 L*3 dichloromethane. Combined organic extract was washed with water and was dried over sodium sulfate. Evaporation of organic solvent afforded 225 g (77%) title compound. m/z (M+1) 263. NMR (CDCl3) D2O exchange: 0.80 (s, 3H); 0.98 (s, 3H); 1.40-1.78 (m, 2H); 2.50 (dt, 2H); 2.90 (m, 1H); 3.80 (t,1H); 4.18 (t, 1H), 5.18 (s,2H); 7.40 (s, 5H).

References: [1]Patent: US6878713,2005,B2 .

2
[ 473838-66-3 ]
[ 1616709-61-5 ]

Yield	Reaction Conditions	Operation in experiment
	With phenyltrimethylammonium tribromide; In dichloromethane; at 20℃; for 4h;	Benzyl 3,3-dimethyl-4-oxopiperidine-1-carboxylate (0.7 g, 2.7 mmol) in DCM (10 ml) was mixed with phenyltrimethylammoniuin tribromide (1.1 g, 3.0 mmol) and stirred at room temperature for 4 hours. Mixture was diluted with DCM, and washed with water and dried over anhydrous sodium sulfate. The crude mixture was concentrated, diethyl ether added, and the resulting precipitate filtered off. The solution was concentrated to afford the titled compound, and used in the next step without further purification.
	With phenyltrimethylammonium tribromide; In dichloromethane; at 20℃; for 4h;	Benzyl 3,3-dimethyl-4-oxopiperidine-l-carboxylate (0.7 g, 2.7 mmol) in DCM (10 ml) was mixed with phenyltrimethylammonium tribromide (1.1 g, 3.0 mmol) and stirred at room temperature for 4 hours. Mixture was diluted with DCM, and washed with water and dried over anhydrous sodium sulfate. The crude mixture was concentrated, diethyl ether added, and the resulting precipitate filtered off. The solution was concentrated to afford the titled compound, and used in the next step without further purification.
	With phenyltrimethylammonium tribromide; In tetrahydrofuran; at 15℃; for 1h;	Phenyltrimethylamine tribromide (1.44 g, 3.83 mmol, 1.00 eq) was added to a solution of <strong>[473838-66-3]benzyl 3,3-dimethyl-4-oxopiperidine-1-carboxylate</strong> (1.10 g, 4.21 mmol, 1.10 eq) in THF (10.00 mL). The mixture was stirred at 15 C for 1 hour. The mixture was quenched by adding water (10 mL) and then extracted with ethyl acetate (20 mL). The combined organic layers were washed with brine (10 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure to deliver the crude benzyl 5-bromo-3,3-dimethyl-4-oxopiperidine-1-carboxylate (1.40 g, crude) as a yellow oil which was used directly in the next step.

References: [1]Patent: WO2014/101120,2014,A1 .Location in patent: Paragraph 0215.
[2]Patent: WO2014/105666,2014,A1 .Location in patent: Paragraph 0220.
[3]Patent: WO2014/101373,2014,A1 .Location in patent: Page/Page column 108.
[4]Patent: EP3252059,2017,A1 .Location in patent: Paragraph 0530; 0537; 0538.

3
[ 473838-66-3 ]
benzyl 2,7,7-trimethyl-6,7-dihydrooxazolo[5,4-c]pyridine-5(4H)-carboxylate [ No CAS ]

References: [1]Patent: WO2014/101120,2014,A1 .

4
[ 473838-66-3 ]
[ 1616709-63-7 ]

References: [1]Patent: WO2014/101120,2014,A1 .

5
[ 473838-66-3 ]
7-methoxy-2-(2-(2,7,7-trimethyl-6,7-dihydro-oxazolo[5,4-c]pyridin-5(4H)-yl)ethyl)-[1,2,4]triazolo[1,5-c]quinazolin-5-amine trifluoroacetate [ No CAS ]

References: [1]Patent: WO2014/101120,2014,A1 .

6
[ 19099-93-5 ]
[ 74-88-4 ]
[ 473838-66-3 ]

Yield	Reaction Conditions	Operation in experiment
38.86%	With sodium hydride; In tetrahydrofuran; at 30℃; for 16h;Inert atmosphere;	At 0C, to a solution of benzyl 4-oxopiperidine-1-carboxylate (2.00 g, 8.57 mmol, 1.00 equivalent) in tetrahydrofuran(25 mL) were added sodium hydride (719.88 mg, 18.00 mmol, 2.10 equivalents) and potassium iodide (3.80g, 26.74 mmol, 3.12 equivalents) in one portion. The mixture was stirred at 30C for 16 hours. LC/MS showed completionof the reaction. The reaction mixture was added a solution of ammonium chloride (50 mL) thereto and then subjectedto extraction using ethyl acetate (50 mL32). The organic phase was concentrated and dried. The obtained residue waspurified by preparative TLC plate (petroleum ether: ethyl acetate = 6: 1) to give the title compound (870.00 mg, 3.33mmol, 38.86% yield) as a transparent oil. 1H NMR (400 MHz, Methanol-d4) delta 7.38-7.33 (m, 5H), 5.19 (s, 2H), 3.81-3.77(t, J = 6.4 Hz, 2H), 3.50-3.46 (m, 2H), 2.50 (s, 2H), 1.11-1.04 (m, 6H). LC/MS (ESI) m/z: 284.1 (M+1).
	With sodium hydride; In tetrahydrofuran; at 0℃; for 2h;	Step A: Benzyl 3,3-dimethyl-4-oxopiperidine-l -carboxylate [0214] Benzyl 4-oxopiperidine-l-carboxylate (5g, 21 mmol) in THF (50 ml) was cooled to 0 C. Sodium hydride (1.1 g, 43 mmol), then iodomethane (3.0 ml, 47 mmol) was added slowly. Mixture was stirred at 0 C for 2 hours, then slowly warm up to room temperature and stirred overnight. Saturated aq. NC1 solution was added and the product was extracted with EtOAc. The extract was washed with brine, dried over anhydrous sodium sulfate, and concentrated. The crude product thus obtained was purified by column chromatography on a 100 gram-size silica gel column, eluting with gradient EtOAc/hexane to afford the titled product as colorless oil.
	With sodium hydride; In tetrahydrofuran; at 0 - 20℃;	Benzyl 4-oxopiperidine-1-carboxylate (5g, 21 mmol) in THF (50 ml) was cooled to 0C. Sodium hydride (1.1 g, 43 mrnol), then iodomethane (3.0 ml, 47 mrnol) was added slowly. Mixture was stirred at 0C for 2 hours, then slowly warm up to room temperature and stirred overnight. Saturated aq. NH4C1 solution was added and the product was extracted with EtOAc. The extract was washed with brine, dried over anhydrous sodium sulfate, and concentrated. The crude product thus obtained was purified by column chromatography on a 100 grain-size silica gel column, eluting with gradient EtOAc/hexane to afford the titled product as colorless oil.

With sodium hydride; In tetrahydrofuran; at 0 - 20℃;

Benzyl 4-oxopiperidine-l-carboxylate (5g, 21 mmol) in THF (50 ml) was cooled to 0C. Sodium hydride (1.1 g, 43 mmol), then iodomethane (3.0 ml, 47 mmol) was added slowly. Mixture was stirred at 0C for 2 hours, then slowly warm up to room temperature and stirred overnight. Saturated aq. NH4C1 solution was added and the product was extracted with EtOAc. The extract was washed with brine, dried over anhydrous sodium sulfate, and concentrated. The crude product thus obtained was purified by column chromatography on a 100 gram-size silica gel column, eluting with gradient EtOAc/hexane to afford the titled product as colorless oil.

References: [1]Patent: EP3269715,2018,A1 .Location in patent: Paragraph 0061; 0376; 0378; 0379.
[2]Patent: WO2014/101120,2014,A1 .Location in patent: Paragraph 0214.
[3]Patent: WO2014/105666,2014,A1 .Location in patent: Paragraph 0219.
[4]Patent: WO2014/101373,2014,A1 .Location in patent: Page/Page column 108.

7
[ 473838-66-3 ]
[ 1616709-59-1 ]

References: [1]Patent: WO2014/105666,2014,A1 .

8
[ 473838-66-3 ]
7-methoxy-2-(2-(2,7,7-trimethyl-6,7-dihydrooxazolo[5,4-c]pyridin-5(4H)-yl)ethyl)-[1,2,4]triazolo[1,5-c]quinazolin-5-amine trifluoroacetate [ No CAS ]

References: [1]Patent: WO2014/101373,2014,A1 .

9
[ 324769-06-4 ]
[ 473838-66-3 ]

References: [1]Patent: WO2017/189386,2017,A1 .
[2]Patent: WO2018/136887,2018,A1 .

10
[ 648921-37-3 ]
[ 501-53-1 ]
[ 473838-66-3 ]

Yield	Reaction Conditions	Operation in experiment
78.5%	With sodium hydrogencarbonate; In tetrahydrofuran; water; at 0 - 15℃; for 12h;	Sodium bicarbonate (1.28 g, 15.28 mmol, 2.50 eq) and CbzCl (1.25 g, 7.33 mmol, 1.20 eq) was added to a mixed solution of 3,3-dimethylpiperidin-4-one; hydrochloride (1.00 g, 6.11 mmol, 1.00 eq) in tetrahydrofuran (5.00 mL) and water (5.00 mL) at 0 C. The mixture was stirred at 15 C for 12 hours. The reaction mixture was extracted with ethyl acetate (20 mL). The combined organic layers were washed with brine (10 mL * 2), dried over sodium sulfate, filtered and concentrated under reduced pressure to deliver benzyl 3,3-dimethyl-4-oxopiperidine-1-carboxylate (1.60 g, 4.81 mmol, 78.66% yield, 78.5% purity) as a colorless oil. 1H NMR (400MHz, CDCl3) delta 7.35-7.25 (m, 6H), 5.11 (s, 2H), 3.72 (t, J = 6.3 Hz, 2H), 3.42 (br. s., 2H), 2.44 (br. s., 2H), 1.02 (br. s., 6H).
	With triethylamine; In dichloromethane; at 0 - 20℃; for 16h;	Preparation of 1-66: A solution of 1-65 (4.20 g, 33.07 mmol) in CH2C12 (80 mL) was charged with benzyl chloroformate (6.70 g, 39.68 mmol) followed by triethyl amine (5.00 g, 49 mmol) over 20 min at 0C. The reaction mixture was stirred at RT for 16 h. The organic layer was washed with saturated NaHCC solution (50 mL), water (100 mL) and brine (50 mL). The organic layer was concentrated under reduced pressure to afford 1-66 as a liquid. MS (MM) m/z 262.1 [M + H]+.
5.80 g	With potassium carbonate; In tetrahydrofuran; water; at 0 - 25℃;	To a solution of 3,3-dimethylpiperidin-4-one hydrochloride (3.6 g, 22.0 mmol, 22.0 mL) in THF (22 mL) was added K2C03 (3 M, 14.6 mL) dissolved in H20 (15 mL). Then the mixture was cooled to 0 C and benzyl chloroformate (4.13 g, 24.2 mmol) was added dropwise. The reaction was stirred at 25 C for 2 h. The residue was poured into water (50 mL), extracted with EtOAc (50 mLx2). The combined organic layer was concentrated as a yellow liquid to afford benzyl 3,3- dimethyl-4-oxo-piperidine-l-carboxylate (5.80 g, 21.09 mmol, 96 % yield). MS (ES+) Ci5Hi9N03 requires: 261, found: 262 [M+H]+. 1H MR (400 MHz, MeOH-d4) delta: 7.42 - 7.35 (m, 5H), 5.19 (s, 2H), 3.78 (s, 2H), 3.53 (s, 2H), 2.50 (t, J= 6.5, 2H), 1.06 (s, 6H).

References: [1]Patent: EP3252059,2017,A1 .Location in patent: Paragraph 0530; 0535; 0536.
[2]Patent: WO2017/189386,2017,A1 .Location in patent: Page/Page column 44.
[3]Patent: WO2018/136887,2018,A1 .Location in patent: Page/Page column 154; 155.

11
[ 473838-66-3 ]
8-{6-chloroimidazo[1,5-a]pyridin-8-yl}-6,6-dimethyl-1,3,8-triazaspiro[4.5]decane-2,4-dione [ No CAS ]