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Chemical Structure| 149423-70-1 Chemical Structure| 149423-70-1

Structure of 149423-70-1

Chemical Structure| 149423-70-1

Benzyl (cis-4-aminocyclohexyl)carbamate

CAS No.: 149423-70-1

4.5 *For Research Use Only !

Cat. No.: A247111 Purity: 95%

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Product Details of [ 149423-70-1 ]

CAS No. :149423-70-1
Formula : C14H20N2O2
M.W : 248.32
SMILES Code : O=C(OCC1=CC=CC=C1)N[C@H]2CC[C@@H](N)CC2
MDL No. :MFCD06657668
InChI Key :JQVBZZUMWRXDSQ-UHFFFAOYSA-N
Pubchem ID :18650082

Safety of [ 149423-70-1 ]

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

Computational Chemistry of [ 149423-70-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 18
Num. arom. heavy atoms 6
Fraction Csp3 0.5
Num. rotatable bonds 5
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 70.13
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

1.83
Log Po/w (WLOGP)?

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

2.03
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.

1.68
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

1.45
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.9

Water Solubility

Log S (ESOL):?

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

-2.45
Solubility 0.883 mg/ml ; 0.00356 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.

-2.8
Solubility 0.392 mg/ml ; 0.00158 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

-3.4
Solubility 0.1 mg/ml ; 0.000403 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.

-6.52 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)

3.01

Application In Synthesis of [ 149423-70-1 ]

* 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 [ 149423-70-1 ]

[ 149423-70-1 ] Synthesis Path-Downstream   1~13

  • 1
  • [ 634-47-9 ]
  • [ 149423-70-1 ]
  • cis-[4-(4-methyl-quinolin-2-ylamino)-cyclohexyl]-carbamic acid benzyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
53% With IEA; In isopropyl alcohol; at 170.0℃; for 5.0h; To a solution of <strong>[149423-70-1]cis-(4-amino-cyclohexyl)-carbamic acid benzyl ester</strong> (0.5 g, 0.0020 mol) in 1 ml_ 2-propanol was added 2-chloro-4-methyl-quinoline (0.43 g, 0.0024 mol) and IEA (526 uL, 0.0030 mol). The mixture was heated in a microwave synthesizer at 170 C for 5 hours. The reaction was repeated 7 more times (4 g total material) and the reaction mixtures were pooled. The solvent was evaporated and the material subjected to chromatography (2-4 % 2M NH3 in MeOH / CH2Cl2) to yield cis-[4-(4-methyl-quinolin-2-ylamino)-cyclohexyl]-carbamic acid benzyl ester (3.3 g, 53%) as a colorless oil. ESI MS m/e 390.2 M + H+; 1H NMR (400 MHz, DMSO-d6) delta 7.71 (d, J = 8 Hz, 1 H), 7.46-7.39 (m, 2 H), 7.37-7.19 (m, 7 H), 6.68 (m, 2 H), 5.01 (s, 2 H), 4.07 (m, 1 H), 3.46 (m, 1 H), 2.44 (s, 3 H), 1.79-1.71 (m, 2 H), 1.70-1.59 (m, 6 H).
  • 2
  • [ 509143-03-7 ]
  • [ 149423-70-1 ]
YieldReaction ConditionsOperation in experiment
97% With trifluoroacetic acid; In dichloromethane; at 20.0℃; for 4.0h; Step B: Synthesis of cis-(4-amino-cyclohexyl)-carbamic acid benzyl ester. To a solution of cis-(4-tert-butoxycarbonylamino-cyclohexyl)-carbamic acid benzyl ester (6.2 g, 0.018 mol) in 40 mL CH2Cl2 was added TFA (2.7 mL, 0.36 mol). The solution was stirred at room temperature for 4 hours. The excess solvent was evaporated off and the resulting oil was dissolved in 30 mL CH2Cl2. The organic layer was extracted with 30 mL of a dilute NaOH (aq) / NaHCO3 (aq) solution. The aqueous layer was back extracted twice with CH2Cl2 and the organic layers combined, dried over MgSO4, and concentrated to yield cis-(4-amino-cyclohexyl)-carbamic acid benzyl ester (4.3 g, 97%) as a colorless oil. The oil was carried forward without further purification. ESI MS m/e 249.2 M + H+.
  • 3
  • [ 149423-70-1 ]
  • [ 2927-71-1 ]
  • [ 1192712-34-7 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 20.0℃; for 20.0h; To a mixture of 2,4-dichloro-5-fluoropyrimidine (226 mg, 1.35 mmol) and benzyl (ls,4s)-4-aminocyclohexylcarbamate (335 mg, 1.35 mmol) in CH3CN (6 mL), DIEA (0.600 mL, 3.45 mmol) was added. The mixture was stirred at room temperature for 20 h. Water and EtOAc were added. The organic phase was separated, washed with IN HCl, dried over Na2SO4, concentrated in vacuo to give benzyl (ls,4s)-4-(2-chloro-5-fluoropyrimidin-4- ylamino)cyclohexylcarbamate (511 mg).
  • 4
  • [ 36082-50-5 ]
  • [ 149423-70-1 ]
  • [ 1192712-36-9 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 20.0℃; for 20.0h; To a mixture of 2,4-dichloro-5-bromopyrimidine (244 mg, 1.07 mmol) and benzyl (ls,4s)-4-aminocyclohexylcarbamate (266 mg, 1.07 mmol) in CH3CN (5 mL), DIEA (0.373 <n="192"/>mL, 2.14 mmol) was added. The mixture was stirred at room temperature for 20 h. Water and EtOAc were added. The organic phase was separated, washed with IN HCl, then with 5% NaHCCbeta, dried over Na2SO4, concentrated in vacuo to give benzyl (ls,4s)-4-(5-bromo-2- chloropyrimidin-4-ylamino)cyclohexylcarbamate
  • 5
  • [ 149423-69-8 ]
  • [ 149423-70-1 ]
YieldReaction ConditionsOperation in experiment
With water; triphenylphosphine; In tetrahydrofuran; at 70.0℃; for 20.0h; To a solution of benzyl (ls,4s)-4-azidocyclohexylcarbamate (0.410 g, 1.50 mmol) in THF (8 mL) and H2O (0.100 mL, 5.56 mmol) at room temperature, Ph3P (0.590 g, 2.25 mmol) was added. The solution was stirred at 7O0C for 20 h. EtOAc and IN HCl were added. The aqueous phase was separated, washed with EtOAc. It was then basified with 5N NaOH to pH 12. The free amine product was extracted with EtOAc. The EtOAc solution was dried over Na2SO4, and concentrated in vacuo to give benzyl (ls,4s)-4-aminocyclohexylcarbamate (0.270 g).
  • 6
  • [ 149423-70-1 ]
  • [ 247570-24-7 ]
  • 7
  • [ 149423-70-1 ]
  • [ 1439908-80-1 ]
  • 8
  • [ 149423-70-1 ]
  • [ 1439908-81-2 ]
  • 9
  • [ 149423-70-1 ]
  • [ 1439908-82-3 ]
  • 10
  • [ 149423-70-1 ]
  • C22H30N6O3 [ No CAS ]
  • 11
  • [ 149423-70-1 ]
  • [ 1439907-37-5 ]
  • 12
  • [ 149423-70-1 ]
  • [ 24424-99-5 ]
  • [ 509143-03-7 ]
YieldReaction ConditionsOperation in experiment
2.47 g In dichloromethane; for 1.0h; Amine D1.1 (Prepared as described in Bauer, Shawn M.; Jia, Zhaozhong J.; Song, Yonghong; Xu, Qing; Mehrotra, Mukund; Rose, Jack W.; Huang, Wolin; Venkataramani, Chandrasekar; Pandey, Anjali. PCT mt. Appi. (2009), W02009145856A1.) (1.92 g, 7.7 mmol) was diluted with dichioromethane (30 mL) affording an opaque solution. To this was added di-tbutyl dicarbonate (2.0 g, 9.3 mmol) in two portions. The resulting solution was then stirred for approximately 1 hr at which time the reaction was determined to be complete by UPLC. The reaction mixture was then concentrated and dried in vacuo overnight affording 2.47 g of the diprotected diamine as a light pink syrup. MS found for C11H21N202 as (M - Boc+2H) 249.2 and (M+Na)+ = 371.4.
  • 13
  • [ 50-00-0 ]
  • [ 149423-70-1 ]
  • (±)-cis-(4-dimethylaminocyclohexyl)carbamic acid benzyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
With formic acid; In water; for 4.0h;Reflux; A solution of (±)-cis-1-N-cbz-1 ,4-cyclohexyldiamine (500 mg, 2.0 mmol, 1 eq.) in formaldehyde (36.5% in H20, 15 mL) and formic acid (0.25 mL, 6.6 mmol, 3.3 eq.) was heated at reflux for 4 hours. The mixture was allowed to cool to r.t. and poured into a sat. NaHC03 soln. (50 mL). The mixture was extracted with AcOEt (3 x 30 mL). The comb. org. phases were dried over MgS04 and concentrated in vacuo. The residue was purified by prep. HPLC (column: Waters X-Bridge, 30x75 mm, 10 muetaiota, UV/MS, basic conditions) to give (±)-cis-(4-dimethylamino-cyclohexyl)-carbamic acid benzyl ester as a white solid. LC-MS 3: tR = 0.82 min; [M+H]+ = 277.0
 

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