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Chemical Structure| 365996-30-1 Chemical Structure| 365996-30-1
Chemical Structure| 365996-30-1

tert-Butyl ((1S,2R)-2-aminocyclohexyl)carbamate

CAS No.: 365996-30-1

4.5 *For Research Use Only !

Cat. No.: A140823 Purity: 96%

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Product Details of [ 365996-30-1 ]

CAS No. :365996-30-1
Formula : C11H22N2O2
M.W : 214.30
SMILES Code : O=C(OC(C)(C)C)N[C@@H]1[C@H](N)CCCC1
MDL No. :MFCD09952105
InChI Key :AKVIZYGPJIWKOS-BDAKNGLRSA-N
Pubchem ID :1514389

Safety of [ 365996-30-1 ]

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

Calculated chemistry of [ 365996-30-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 15
Num. arom. heavy atoms 0
Fraction Csp3 0.91
Num. rotatable bonds 4
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 60.1
TPSA ?

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

64.35 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.54
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

1.32
Log Po/w (WLOGP)?

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

1.78
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.

1.15
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

0.64
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.49

Water Solubility

Log S (ESOL):?

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

-1.74
Solubility 3.93 mg/ml ; 0.0184 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-2.27
Solubility 1.14 mg/ml ; 0.00534 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

-1.69
Solubility 4.42 mg/ml ; 0.0206 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

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.

-6.67 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<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)

3.02

Application In Synthesis of [ 365996-30-1 ]

* 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 [ 365996-30-1 ]

[ 365996-30-1 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 121282-70-0 ]
  • [ 365996-30-1 ]
YieldReaction ConditionsOperation in experiment
5.24 g Reference Example 128 Triphenylphosphine (14.3 g) was added to a THF (190 ml) solution containing tert-butyl S,2S)-2-hydroxycyclohexyl) carbamate (10.0 g), followed by ice cooling. Diethyl azodicarboxylate (40% in toluene) (24.3 g) and DPPA (15.3 g) were added dropwise to the reaction solution, followed by stirring at room temperature for 1 hour. The reaction solution was left overnight. The solvent was distilled away under reduced pressure. Water was added and then a 20% sodium hydroxide aqueous solution was added. Then, the organic layers were collected. Water (30 ml) was added to the obtained organic layers, followed by heating to 60 C. A THF (40 ml) solution containing triphenylphosphine (14.3 g) was added dropwise, followed by reflux for 2.5 hours. The solvent was distilled away under ordinary pressure. Toluene was added and the pH was adjusted with 3M hydrochloric acid to pH=1 or less. Then, the resulting aqueous layers were collected, ethyl acetate was added, and the pH was adjusted with a 20% sodium hydroxide aqueous solution to pH 12. The organic layers were collected and dried over anhydrous sodium sulfate. Light yellow oily matter of tert-butyl ((1S,2R)-2-aminocyclohexyl)carbamate (5.24 g) was thus obtained.
  • 2
  • [ 3177-24-0 ]
  • [ 365996-30-1 ]
  • [ 1439909-36-0 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 45℃; for 0.333333h; 2,4-Dichloropyrimidine-5-carbonitrile (4.46 g, 25.6 mmol) was dissolved in 100 mL DMF. To it were added tert-butyl ((lS,2R)-2-aminocyclohexyl)carbamate (4.99 g, 23.3 mmol) and DIEA (6.1 mL, 35. 0 mmol). The mixture was stirred at 45°C for 20 m to afford two coupling product in about equal amount in quantitative yield. The mixture was concentrated in vacuo, diluted with EtOAc, washed with brine twice, dried, concentrated and subjected to flash column to separate tert-butyl ((lS,2R)-2-((4-chloro-5-cyanopyrimidin-2- yl)amino)cyclohexyl)carbamate.
  • 3
  • [ 1224944-51-7 ]
  • [ 365996-30-1 ]
  • methyl 5-[[(1R,2S)-2-(tert-butoxycarbonylamino)cyclohexyl]amino]pyrazolo[1,5-a]pyrimidine-3-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
46% at 90.0℃; for 0.5h;Sealed tube; Microwave irradiation; A microwave vial was charged with <strong>[1224944-51-7]methyl 5-chloropyrazolo[1,5-a]pyrimidine-3-carboxylate</strong> (500 mg, 2.36 mmol), tert-butyl N-[(1S,2R)-2-aminocyclohexyl]carbamate (506 mg, 2.36 mmol), and methanol (4.7 mL). The vial was sealed and stirred at 90 C for 30 min in the microwave, resulting in a suspension. The reaction mixture was concentrated in vacuo and the crude product was purified by column chromatography (0-100% isopropyl acetate/heptane) to afford methyl 5- [[(1R,2S)-2-(tert-butoxycarbonylamino)cyclohexyl]amino]pyrazolo[1,5-a]pyrimidine-3- carboxylate (420.2 mg, 1.08 mmol, 46% yield) as a white solid. MS: m/z = 390 (M+1).
  • 4
  • [ 1224944-51-7 ]
  • [ 365996-30-1 ]
  • 5-(((1R,2S)-2-((tert-butoxycarbonyl)amino)cyclohexyl)amino)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid [ No CAS ]
 

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