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Chemical Structure| 1184919-69-4 Chemical Structure| 1184919-69-4

Structure of 1184919-69-4

Chemical Structure| 1184919-69-4

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Product Details of [ 1184919-69-4 ]

CAS No. :1184919-69-4
Formula : C5H12ClNO
M.W : 137.61
SMILES Code : OC1CC(N)CC1.[H]Cl
MDL No. :MFCD16619116

Safety of [ 1184919-69-4 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 1184919-69-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 8
Num. arom. heavy atoms 0
Fraction Csp3 1.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 2.0
Molar Refractivity 34.87
TPSA ?

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

46.25 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.0
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

0.38
Log Po/w (WLOGP)?

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

0.66
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.

0.21
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

0.14
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.28

Water Solubility

Log S (ESOL):?

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

-0.93
Solubility 16.1 mg/ml ; 0.117 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.

-0.92
Solubility 16.7 mg/ml ; 0.121 mol/l
Class?

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

Very 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

0.2
Solubility 220.0 mg/ml ; 1.6 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.

-6.87 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

1.0
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)

1.84

Application In Synthesis of [ 1184919-69-4 ]

* 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.

  • Downstream synthetic route of [ 1184919-69-4 ]

[ 1184919-69-4 ] Synthesis Path-Downstream   1~15

  • 1
  • [ 930-30-3 ]
  • [ 1184919-69-4 ]
  • 2
  • [ 1029691-06-2 ]
  • [ 1184919-69-4 ]
  • 3
  • [ 1445796-28-0 ]
  • [ 1184919-69-4 ]
YieldReaction ConditionsOperation in experiment
82% With hydrogenchloride; In methanol; for 2.0h;Reflux; A mixture of compound 4 (8.0 g, 34 mmol) in MeOH (100 mL) was added concentrated HCl (10 mL), and heated to reflux for 2 h. The mixture was concentrated in vacuo. The residue was dissolved with water and washed with EA. The aqueous phase was concentrated in vacuo to give the desired product with HCl salt (2.8 g, 82 %). lH NMR (400 MHz, CDC13): delta ppm: 4.33 (bs, 1H), 3.66 (bs, 1H), 2.08 - 2.16 (m, 2H), 1.74 -1.90 (m, 4 H).
  • 4
  • [ 1184919-69-4 ]
  • [ 1445796-58-6 ]
  • [ 1445791-53-6 ]
YieldReaction ConditionsOperation in experiment
48% With triethylamine; In acetonitrile; at 20℃; for 2.0h; To a solution of Compound 6 (626 mg, 1.72 mmol) and Compound 5 (174 mg, 1.72 mmol) in MeCN (7 mL) was added Et3N (260 mg, 2.58 mmol) at rt, and the mixture was stirred at rt for 2 h. The solution was concentrated in vacuo. The organic phase was concentrated in vacuo to give the crude product, which was purified by prep- HPLC to give the desired product (355 mg, 48%). H NMR (MeOD-d4 400MHz): 8.47-8.45(m, 1H), 8.230-8.22 (m, 1H), 7.98-7.96 (m, 1H), 7.62-7.61 (m, 1H), 7.50-7.48 (m, 1H), 7.46-7.26(m, 1H), 4.13-4.10 (m, 1H), 3.72- 3.68 (m, 1H), 2.10-2.08 (m, 1H), 1.08-1.64 (m, 4H).1.64-1.43 (m, 1H). LCMS: 431.0 [M+l].
  • 5
  • [ 1184919-69-4 ]
  • [ 1005-56-7 ]
  • [ 1443928-57-1 ]
YieldReaction ConditionsOperation in experiment
26% With triethylamine; In dichloromethane; at 0 - 20℃; for 2.0h; Preparation of Intermediate A: Rac-3-aminopentanol hydrochloride (100 mg, 0.7267 mmol), dissolved in DCM (8 mL), was cooled to 0 C and then treated with triethylamine (140 pL, 1.018 mmol) followed by dropwise addition of o-phenylchlorothiocarbonate (1 10 pL, 0.7994 mmol). The reaction mixture was allowed to warm to rt over 2h and concentrated. The residue was purified by ISCO chromatography (EtOAc/hexanes) to give Intermediate A as yellow oil (45 mg, 26 %).
  • 6
  • [ 1184919-69-4 ]
  • [ 1443926-66-6 ]
  • 7
  • [ 40296-46-6 ]
  • [ 1184919-69-4 ]
  • ethyl 6-chloro-4-((3-hydroxycyclopentyl)amino)nicotinate [ No CAS ]
YieldReaction ConditionsOperation in experiment
69% With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl acetamide; at 100℃; for 4.0h; Step 1: To a solution of <strong>[1184919-69-4]3-aminocyclopentanol hydrochloride</strong> (1.05 g, 7.63 mmol) and ethyl 4,6-dichloronicotinate (1.679 g, 7.63 mmol) in DMA (10 mL) was added DIPEA (6.66 mL, 38.2 mmol), then reaction mixture was heated at 100 C. for 4 h. Water (50 mL) was added and the mixture was extracted with ethyl acetate (2×150 mL). The combined organic layers were washed with cold water (2×50 mL) and brine solution (40 mL) then dried over Na2SO4. The filtrate was concentrated and the product was purified using silica gel eluting 40% ethyl acetate in hexane to afford ethyl 6-chloro-4-((3-hydroxycyclopentyl)amino)nicotinate (1.5 g, 5.27 mmol, 69% yield), which was taken for the next step without chiral separation. 1H NMR (400 MHz, DMSO-d6) delta ppm 8.54 (br. s., 1H) 8.03-8.42 (m, 1H) 6.78 (d, J=9.54 Hz, 1H) 4.62-4.77 (m, 1H) 3.99-4.33 (m, 4H) 1.86-2.29 (m, 3H) 1.38-1.78 (m, 3H) 1.31 (td, J=7.03, 1.00 Hz, 3H); LCMS(M+H) 285.0.
With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl acetamide; at 100℃; for 4.0h; To a solution of <strong>[1184919-69-4]3-aminocyclopentanol hydrochloride</strong> (1.05 g, 7.63 mmol) and ethyl 4,6-dichloronicotinate (1.679 g, 7.63 mmol) in DMA (10 mL) was added DIPEA (6.66 mL, 38.2 mmol), then reaction mixture was heated at 100 C for 4 hr. Water(5OmL) was added and the mixture was extracted with ethyl acetate (2 x 150 mL). The combined organic layers were washed with cold water (2 x 50 mL) and brine solution (40 mL) then dried over Na2SO4. The filtrate was concentrated and the product was purified using silica gel eluting 40% ethyl acetate in hexane to afford ethyl 6-chloro-4-((3- hydroxycyclopentyl)amino)nicotinate (1.5 g, 5.27 mmol, 69% yield), which was taken forthe next step without chiral separation. ?H NMR (400 MHz, DMSO-d6) oe ppm 8.54 (br.s., 1 H) 8.03-8.42 (m, 1 H) 6.78 (d, J=9.54 Hz, 1 H) 4.62-4.77 (m, 1 H) 3.99-4.33 (m, 4H) 1.86-2.29 (m, 3 H) 1.38-1.78 (m, 3 H) 1.31 (td, J=7.03, 1.00 Hz, 3 H); LCMS(M+H)285.0.
  • 8
  • [ 40296-46-6 ]
  • [ 1184919-69-4 ]
  • ethyl 6-chloro-4-((3-fluorocyclopentyl)amino)nicotinate [ No CAS ]
  • 9
  • [ 1184919-69-4 ]
  • 4'-[(2S)-2-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]amino}-3-[3-fluoro-4-(2H-tetrazol-5-yl)phenyl]amino}propyl]-2-methylbiphenyl-4-carboxylic acid [ No CAS ]
  • tert-butyl [(trans-4-[(2S)-1-[3-fluoro-4-(2H-tetrazol-5-yl)phenyl]amino}-3-{4'-[(3-hydroxycyclopentyl)carbamoyl]-2'-methylbiphenyl-4-yl}-1-oxopropane-2-yl]carbamoyl}cyclohexyl)methyl]carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
15% With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 30℃; for 48.0h; A solution of 150 mg (0:21 mmol) of 4'-[(2S)-2-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]amino}-3-[3-fluoro-4-(2H-tetrazol-5-yl)phenyl]amino}propyl]-2-methylbiphenyl-4-carboxylic acid 59 mg (0:43 mmol) of 3-aminocyclopentanolhydrochloride in 2.0 ml of dimethylformamide was treated with 0:11 ml (0.64 mmol) Nu, Nu-diisopropylethylamine and 163 mg (0:43 mmol) of N - [(dimethylamino) (3 / i- [l, 2,3] triazolo [4,5-b]pyridin-3-yloxy) methylidene] -N-methylmethanaminium hexafluorophosphate were added. It was stirred at 30 C for 48 h. The reaction mixture was chromatographically separated via HPLC(Method 11). The product-containing fractions were combined and lyophilized. This gave 29 mg(15% d. Th.) Of the title compound.
  • 10
  • [ 1184919-69-4 ]
  • 3-(6-bromo-3-aminoquinolin-4-yl)aminocyclopentanol [ No CAS ]
  • 11
  • [ 1184919-69-4 ]
  • 8-bromo-1-(3-hydroxycyclopentyl)-1H-imidazo[4,5-c]quinolin-2(3H)-one [ No CAS ]
  • 12
  • [ 1184919-69-4 ]
  • 8-bromo-3-methyl-1-(3-hydroxycyclopentyl)-1H-imidazo[4,5-c]quinolin-2(3H)-one [ No CAS ]
  • 13
  • [ 1184919-69-4 ]
  • 1-(3-hydroxycyclopentyl)-3-methyl-8-(6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)-1H-imidazo[ 4,5-c]quinolin-2(3H)-one [ No CAS ]
  • 14
  • [ 723281-72-9 ]
  • [ 1184919-69-4 ]
  • 3-(6-bromo-3-nitroquinolin-4-yl)aminocyclopentanol [ No CAS ]
YieldReaction ConditionsOperation in experiment
100% With triethylamine; In dichloromethane; at 20℃; for 2.5h; (XIX) Scheme XIX Intermediate 432: 3-(6-bromo-3-nitroquinolin-4-yl)aminocyclopentanol 1.69 g (5.9 mmol) of Compound 3 and 1.226 g (8.9 mmol) of <strong>[1184919-69-4]3-aminocyclopentanol hydrochloride</strong> (a mixture of cis and trans isomers) were dissolved in 20 ml of dichloromethane, added with 3.3 ml (23.6 mmol) of triethylamine, stirred at room temperature for 2.5 h to precipitate out solids, filtered, washed with a small amount of dichloromethane, and pumped to dryness to afford a yellow solid (2.154 g). Yield: 100%. LC-MS: 351.8, 353.8 [M+1]+, tR = 1.822 min.
  • 15
  • [ 1184919-69-4 ]
  • 2-(5-amino-2-(furan-2-yl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-7-yl)-2-phenylpropanoic acid [ No CAS ]
  • 2-(5-amino-2-(furan-2-yl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-7-yl)-N-(3-hydroxycyclopentyl)-2-phenylpropanamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
38% With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 20℃; for 2.0h; A mixture of 2- (5-amino-2- (furan-2-yl) -7H-pyrazolo [4, 3-e] [1, 2, 4] triazolo [1, 5-c] pyrimidin-7-yl) -2-phenylpropanoic acid (50 mg, 0.13 mmol) , <strong>[1184919-69-4]3-aminocyclopentan-1-ol hydrochloride</strong> (21 mg, 0.15 mmol) , HATU (57 mg, 0.15 mmol) and DIPEA (34 mg, 0.26 mmol) in DMF (5 mL) was stirred at rt for 2 hrs. The solution was added with water (5 mL) , extracted with ethyl acetate (10 mL) and washed with brine (10 mL) . The organic layer was dried, concentrated and purified by preparative TLC (EtOAc) to get the desired product (23 mg, 38%) . 1H NMR (400 MHz, DMSO-d6) delta 8.21 (d, J=12.0Hz, 1H) , 7.97 (br. s, 2H) , 7.95 (s, 1H) , 7.43-7.39 (m, 1H) , 7.32-7.24 (m, 4H) , 7.18-7.12 (m, 2H) , 6.74 (d, J=4.0Hz, 1H) , 4.47 (d, J=4.0Hz, 1H) , 4.18 (br. s, 1H) , 4.00 (s, 1H) , 2.27 (s, 3H) , 1.92-1.73 (m, 2H) , 1.67-1.59 (m, 2H) , 1.40-1.37 (m, 2H) ppm. MS: M/e 473 (M+1) +
 

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