Home Cart Sign in  
Chemical Structure| 912444-89-4 Chemical Structure| 912444-89-4

Structure of 912444-89-4

Chemical Structure| 912444-89-4

*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 [ 912444-89-4 ]

CAS No. :912444-89-4
Formula : C14H23NO4
M.W : 269.34
SMILES Code : O=C(N1CCC(C(OCC)=O)=CCC1)OC(C)(C)C
MDL No. :MFCD11114566
InChI Key :OQQBVXIIESRTAD-UHFFFAOYSA-N
Pubchem ID :25194565

Safety of [ 912444-89-4 ]

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

Computational Chemistry of [ 912444-89-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 19
Num. arom. heavy atoms 0
Fraction Csp3 0.71
Num. rotatable bonds 6
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 76.63
TPSA ?

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

55.84 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

3.49
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

2.2
Log Po/w (WLOGP)?

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

2.13
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.

1.75
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

1.68
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.25

Water Solubility

Log S (ESOL):?

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

-2.5
Solubility 0.852 mg/ml ; 0.00316 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.

-3.01
Solubility 0.265 mg/ml ; 0.000985 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

-2.02
Solubility 2.6 mg/ml ; 0.00964 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

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

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.

-6.38 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

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<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)

3.34

Application In Synthesis of [ 912444-89-4 ]

* 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 [ 912444-89-4 ]

[ 912444-89-4 ] Synthesis Path-Upstream   1~4

  • 1
  • [ 912444-88-3 ]
  • [ 912444-89-4 ]
YieldReaction ConditionsOperation in experiment
95% With 1,8-diazabicyclo[5.4.0]undec-7-ene In benzene at 60℃; for 1 h; EXAMPLE 42D; 1-tert-butyl 4-ethyl 2,3,6,7-tetrahydro-1H-azepine-1,4-dicarboxylate A solution of example 42C (0.77 g, 2.1 mmol) in 30 mL of benzene was treated with DBU (0.9 ml ) at 60° C. for 1 hour. After cooling, the reaction mixture was concentrated and the residue was purified by flash column chromatography (30percent EtOAc in hexane) to give the title product (540 mg, 95percent yield). MS (DCI/NH3) m/z 270 (M+H)+.
3.31 g With 1,8-diazabicyclo[5.4.0]undec-7-ene In toluene at 60℃; A solution of 1-(tert-butyl) 4-ethyl 5-((methylsulfonyl)oxy)azepane-1,4-dicarboxylate (5.0 g, 13.7 mmol)and DBU (10 mL) in toluene (50 mL) was heated to 60° C.and stirred overnight. Upon completion of the reaction, thereaction mixture was quenched with water (70 mL) andextracted with EtOAc (100 mLx3). The combined organicphase was dried over Na2S04 and concentrated underreduced pressure. The residue was purified by silica-gelcolunm chromatography to afford 3.31 g of 1-(tert-butyl)4-ethyl 2,3,6,7 -tetrahydro-1H-azepine-1 ,4-dicarboxylate asa yellow oil. LC-MS (ESI+ ): m/z 292 [M+Nat.
56.8 g With 1,8-diazabicyclo[5.4.0]undec-7-ene In tetrahydrofuran To a solution of 1-tert-butyl 4-ethyl 5-oxoazepane-1,4-dicarboxylate (13) (94.5 g, 0.331 mol) in MeOH (1.3 L), NaBH4 (3.74 g, 0,099 mol) was added portionwise at 0 °C and the mixture was stirred at the same temperature for additional 1 h. The resulting solution was concentrated under vacuum. The residue was diluted with H2O (700 mL) and extracted with EtOAc (3300 mL). The combined organic extracts were washed with H2O (200 mL), brine (200 mL), dried over anhydrous Na2SO4 and evaporated under reduced pressure to give 80.1 g of crude product, that was used in the next step without further purification. To a solution of the crude 1-tert-butyl 4-ethyl 5-hydroxyazepane-1,4-dicarboxylate (80.1 g) in CH2Cl2 (1.1 L), NEt3 (117 mL, 0.834 mol) was added at 0 °C. Methanesulfonyl chloride (36.5 mL, 0.474 mol) was added dropwise while the temperature was maintained below 5 °C and the solution was stirred at rt for 4 h. The resulting mixture was treated with 10percent aq NaHCO3 (500 mL), organic phase was separated, and the aqueous phase was extracted with CH2Cl2 (3300 mL). The combined organic layers were dried over anhydrous Na2SO4 and evaporated under reduced pressure to give 95.3 g of crude product, which was used in the next step without further purification. S4 To a solution of obtained crude 1-tert-butyl 4-ethyl 5-((methylsulfonyl)oxy)azepane-1,4-dicarboxylate (95.3 g) in THF (2.1 L), DBU (54.6 mL, 0.365 mol) was added in one portion and the reaction mixture was stirred overnight. The resulting solution was diluted with EtOAc (500 mL), washed with brine (4500 mL), dried over anhydrous Na2SO4 and evaporated under reduced pressure to give the title product. Yield: 56.8 g (64 percent); colorless oil. The compound existed as ca. 1:1 mixture of rotamers.
References: [1] Patent: US2006/229289, 2006, A1, . Location in patent: Page/Page column 22.
[2] Angewandte Chemie - International Edition, 2013, vol. 52, # 23, p. 6072 - 6075[3] Angew. Chem., 2013, vol. 125, # 23, p. 6188 - 6191.
[4] Patent: US2018/258065, 2018, A1, . Location in patent: Paragraph 0149.
[5] Tetrahedron Letters, 2018, vol. 59, # 52, p. 4611 - 4615.
  • 2
  • [ 912444-87-2 ]
  • [ 912444-89-4 ]
YieldReaction ConditionsOperation in experiment
66% With methanesulfonyl chloride; 1,8-diazabicyclo[5.4.0]undec-7-ene In toluene at 110℃; for 2 h; Example 18C
1-tert-butyl 4-ethyl 2,3,6,7-tetrahydro-1H-azepine-1,4-dicarboxylate
To a solution of EXAMPLE 18B (21 g, 73 mmol), DBU (22 g, 146 mmol) in toluene (200 mL) was added dropwise MsCl (14.56 g, 128 mmol).
After the dropwise addition was completed, the mixture was stirred at 110° C. for 2 h, and cooled to room temperature, and then water (200 mL) was added to quench.
The aqueous layer was extracted with EtOAc (200 mL*2).
The combined organic layers were washed with water, brine, dried over Na2SO4, filtered and evaporated.
The residue was purified by column chromatograph on silica gel to provide the title compound (13 g, yield: 66percent). LCMS (ESI) m/z: 270 (M+1).
References: [1] Patent: US2017/29430, 2017, A1, . Location in patent: Paragraph 0322.
[2] Angewandte Chemie - International Edition, 2013, vol. 52, # 23, p. 6072 - 6075[3] Angew. Chem., 2013, vol. 125, # 23, p. 6188 - 6191.
[4] Patent: US2018/258065, 2018, A1, .
[5] Tetrahedron Letters, 2018, vol. 59, # 52, p. 4611 - 4615.
  • 3
  • [ 141642-82-2 ]
  • [ 912444-89-4 ]
References: [1] Angewandte Chemie - International Edition, 2013, vol. 52, # 23, p. 6072 - 6075[2] Angew. Chem., 2013, vol. 125, # 23, p. 6188 - 6191.
[3] Patent: US2017/29430, 2017, A1, .
[4] Patent: US2018/258065, 2018, A1, .
[5] Tetrahedron Letters, 2018, vol. 59, # 52, p. 4611 - 4615.
  • 4
  • [ 79099-07-3 ]
  • [ 912444-89-4 ]
References: [1] Patent: US2018/258065, 2018, A1, .
[2] Tetrahedron Letters, 2018, vol. 59, # 52, p. 4611 - 4615.
 

Historical Records

Technical Information

Categories

Related Functional Groups of
[ 912444-89-4 ]

Amides

Chemical Structure| 184368-74-9

A376718 [184368-74-9]

1-tert-Butyl 4-methyl 5,6-dihydropyridine-1,4(2H)-dicarboxylate

Similarity: 0.93

Chemical Structure| 135716-08-4

A108709 [135716-08-4]

tert-Butyl 4-(2-ethoxy-2-oxoethylidene)piperidine-1-carboxylate

Similarity: 0.88

Chemical Structure| 170838-26-3

A361622 [170838-26-3]

2-(1-(tert-Butoxycarbonyl)piperidin-4-yl)benzoic acid

Similarity: 0.82

Chemical Structure| 206111-40-2

A141172 [206111-40-2]

1-tert-Butyl 4-ethyl 3-hydroxy-5,6-dihydropyridine-1,4(2H)-dicarboxylate

Similarity: 0.82

Chemical Structure| 80221-26-7

A146329 [80221-26-7]

Ethyl N-Cbz-4-piperidineacetate

Similarity: 0.80

Esters

Chemical Structure| 184368-74-9

A376718 [184368-74-9]

1-tert-Butyl 4-methyl 5,6-dihydropyridine-1,4(2H)-dicarboxylate

Similarity: 0.93

Chemical Structure| 135716-08-4

A108709 [135716-08-4]

tert-Butyl 4-(2-ethoxy-2-oxoethylidene)piperidine-1-carboxylate

Similarity: 0.88

Chemical Structure| 206111-40-2

A141172 [206111-40-2]

1-tert-Butyl 4-ethyl 3-hydroxy-5,6-dihydropyridine-1,4(2H)-dicarboxylate

Similarity: 0.82

Chemical Structure| 80221-26-7

A146329 [80221-26-7]

Ethyl N-Cbz-4-piperidineacetate

Similarity: 0.80

Chemical Structure| 160809-38-1

A571747 [160809-38-1]

Ethyl N-Cbz-piperidine-4-carboxylate

Similarity: 0.78

Related Parent Nucleus of
[ 912444-89-4 ]

Other Aliphatic Heterocycles

Chemical Structure| 912444-90-7

A157798 [912444-90-7]

1-tert-Butyl 4-ethyl azepane-1,4-dicarboxylate

Similarity: 0.75

Chemical Structure| 130753-13-8

A179822 [130753-13-8]

Benzyl 3-oxo-8-azabicyclo[3.2.1]octane-8-carboxylate

Similarity: 0.68

Chemical Structure| 442877-23-8

A399827 [442877-23-8]

rel-(3AR,5r,6aS)-2-(tert-butoxycarbonyl)octahydrocyclopenta[c]pyrrole-5-carboxylic acid

Similarity: 0.68

Chemical Structure|

[]

Similarity: 0.67

Chemical Structure| 134575-14-7

A431602 [134575-14-7]

rel-Benzyl (1R,5S,6r)-6-(hydroxymethyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate

Similarity: 0.67