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Chemical Structure| 6936-47-6 Chemical Structure| 6936-47-6

Structure of 6936-47-6

Chemical Structure| 6936-47-6

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Product Details of [ 6936-47-6 ]

CAS No. :6936-47-6
Formula : C6H14ClNO
M.W : 151.63
SMILES Code : Cl[H].N[C@H]1CCCC[C@H]1O
English Name :cis-2-Aminocyclohexanol hydrochloride
MDL No. :MFCD00143981

Safety of [ 6936-47-6 ]

Computational Chemistry of [ 6936-47-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
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 39.68
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

0.74
Log Po/w (WLOGP)?

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

1.05
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.

0.57
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

0.39
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.55

Water Solubility

Log S (ESOL):?

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

-1.25
Solubility 8.6 mg/ml ; 0.0567 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.

-1.29
Solubility 7.77 mg/ml ; 0.0512 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

-0.1
Solubility 122.0 mg/ml ; 0.802 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.

-6.7 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)

1.97

Application In Synthesis of [ 6936-47-6 ]

* 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 [ 6936-47-6 ]

[ 6936-47-6 ] Synthesis Path-Downstream   1~14

  • 1
  • [ 1015480-67-7 ]
  • [ 200352-28-9 ]
  • [ 1015480-48-4 ]
YieldReaction ConditionsOperation in experiment
In 1-methyl-pyrrolidin-2-one at 140℃; for 0.166667h; Microwave oven; 1 Example 1: (^^^^-^-(S^-Dimethoxy-phenyO-pyrazololi.S-alpyrimidin-S-ylamino]- cyclohexanol:5-Chloro-3-(3,4-dimethoxy-phenyl)-pyrazolo[1 ,5-a]pyrimidine (C) ( 25 mg; 0.086 mmol) and (as amino starting material) cis-2-aminocyclohexanol HCI (ACROS, F26585) (125 mg; 1.09 mMol) are suspended in NMP (0.5 mL) and stirred at 1400C for 10 min at 300 W in an Emry Optimizer (microwave oven from Personal Chemistry AB, Uppsala, Sweden). The reaction mixture is treated with water (2 mL) and extracted with EtOAc (2 x 10 mL). The combined organic layers are washed with a saturated NaHCO3 solution, water, then brine, and then dried (Na2SO4), and concentrated under reduced pressure. Purification is done by chromatography on a 4 g Redisep Sg-100 column (Teledyne ISCO, Inc., Lincoln, Nebraska, USA) eluting with CH2CI2/CH3OH 95:5 (v/v)), to obtain the title compound as beige crystals: MS(ESI+):m/z= 369.1 (M+H)+; HPLC: tRet = 5.33 minutes (System 1).
  • 2
  • [ 832099-55-5 ]
  • [ 200352-28-9 ]
  • [ 837377-75-0 ]
YieldReaction ConditionsOperation in experiment
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In DMF (N,N-dimethyl-formamide) at 20℃; for 18h; 35 Example 35; 5-Fluoro-N-(1R,2S-2-hydroxy-acetyl-cyclohexyl)-2-(3-methylsulfanyl-phenoxy)- nicotinamide; 1- (3-DIMETHYLAMINOPROPYL)-3-ETHYLCARBODIIMIDE HYDROCHLORIDE (240mg, 1. 25MMOL) was added to a solution of 5-FLUORO-2- (3-METHYLSULFANYL-PHENOXY)-NICOTINIC acid (175mg, 0. 627MOL), (1S,2R)-2-amino-cyclohexan-1-ol hydrochloride (100mg, 0. 627MOL), 1-hydroxybenzotriazole (95mg, 0. 704MOL) and triethylamine (350, u1, 2. 51MMOL) in DIMETHYLFORMAMIDE (5ml) under nitrogen at room temperature. The reaction was stirred for 18h and partitioned between diethylether (60ml) and water (60ml). The organic phase was removed and washed with water (30ml), brine (30ml), dried over MGS04 and the solvent was removed under reduced pressure. The residue was purified by flash column chromatography on silica gel eluting with a solvent gradient of ethyl acetate: cyclohexane (10: 90 changing to 80 : 20, by volume) to give 5-FLUORO-N- (1R, 2S-2-HYDROXY-ACETYL-CYCLOHEXYL)-2- (3-METHYLSULFANYL- phenoxy) -nicotinamide (40mg) as an oil. 1H NMR (400MHZ, CD30D) : No.= 8.18-8. 22 (1H, dd), 8.08-8. 11 (1H, d), 7.31-7. 37 (1H, t), 7.13-7. 18 (1H, d), 7.12 (1H, s), 6.92-6. 98 (1H, d), 4.00-4. 08 (1H, m), 3.92-3. 98 (1 H, brs), 2.47 (3H, s), 1. 58-1. 80 (6H, 2xm), 1.35-1. 48 (2H, m) ppm. LRMS (ELECTROSPRAY) : m/z [2M+Na]+ 775, [M-H] + 375. Anal. Found C, 59.40 ; H, 5.62 ; N, 7.22. C19H21FN2O3S. 0. 4mol H20 requires C, 59.48 ; H, 5.73 ; N, 7. 30%.
  • 3
  • [ 76-83-5 ]
  • [ 200352-28-9 ]
  • [ 1236423-06-5 ]
YieldReaction ConditionsOperation in experiment
With triethylamine In hexane; dichloromethane; ethyl acetate 2.A Step A: Step A: Cis-2-triphenylmethylaminocyclohexanol A mixture of cis-2-aminocyclohexanol hydrochloride (4.88 g; 32 mmol) (William S. Johnson and Elliot N. Schubert, J.A.C.S., Vol. 72, pp. 2187-2190 (1950), triphenylmethylchloride (10.7 g; 38.4 mmol) and triethylamine (16 ml; 115 mmol) in 250 ml methylene chloride are refluxed for 3 hrs. then stirred at room temperature overnight. The mixture is poured into H2 O and extracted with CH2 Cl2 (200 ml), dried (Na2 SO4) concentrated in vacuo and flash chromatographed using 9:1 7:1; hexane:EtOAc to obtain cis-2-triphenylmethylaminocyclohexanol which is used directly in the next step.
  • 4
  • [ CAS Unavailable ]
  • [ 200352-28-9 ]
  • [ 1188926-05-7 ]
YieldReaction ConditionsOperation in experiment
Stage #1: cis-2-amino-cyclohexanol hydrochloride With sodium hydroxide In tetrahydrofuran; water at 20℃; for 1h; Stage #2: C15H7Cl2F6NO2 In tetrahydrofuran; water at 20℃; for 1h; 4B.B.b 5-(4-Chloro-phenyl)-6-(2,2,2-trifluoro-ethoxy)-2-trifluoromethyl-nicotinic acid (1.5 g, 3.75 mmol) was dissolved in a mixture of THF (15 ml) and DMF (11.4 μl). To this solution was added with stirring oxalyl chloride (0.52 ml, 6.0 mmol), whereby at room temperature after 1 h the corresponding acid chloride was formed. (1R,2S)-2-Hydroxy-cyclohexyl-ammonium; chloride (608.9 mg, 4.02 mmol) was dissolved in a mixture of THF (6 ml) and water (6 ml). This solution was treated with NaOH 32% (1.74 ml, 18.8 mmol) and stirred at room temperature for 1 h. To this solution was added the above produced acid chloride and stirred at room temperature for 1 h. The reaction mixture was poured onto water (120 ml) and the formed precipitation filtered. The brown crystals were dissolved under reflux in ethanol (12 ml), cooled to room temperature, treated with water (10 ml) yielding after filtration and drying the title compound (1.62 g) as light grey crystals; MS (ISP) 497.1 (M+H)+.
  • 5
  • [ 1189191-18-1 ]
  • [ 200352-28-9 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; water for 1h; Reflux; 4B.B.e (3aR,7aS)-2-Methyl-3a,4,5,6,7,7a-hexahydro-benzooxazol-3-ium; chloride (33 g, 159.7 mmol) were dissolved in a mixture of water (330 ml) and HCl (25%, 229 ml). The solution was heated to reflux for 1 h, cooled to room temperature, filtrated over speedex and the solvent evaporated. The residue was dissolved under reflux in ethanol (150 ml), filtered and the filtrate treated with TBME (300 ml). The formed crystals were filtered and dried to yield the title compound (14.2 g) as white crystals; MS (ISP) 116.1 (M+H)+.
  • 6
  • [ 34619-03-9 ]
  • [ 200352-28-9 ]
  • [ 291533-28-3 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate In tetrahydrofuran; water at 0 - 20℃; Inert atmosphere;
  • 7
  • [ CAS Unavailable ]
  • [ 200352-28-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: (R)-2,2'-diphenyl-3,3'-biphenanthryl-4,4'-diyl phosphate; phenyl trimethylsilyl selenide / toluene / 1 h / 0 °C / Inert atmosphere 2: Phenylselenyl bromide; silver trifluoromethanesulfonate / dichloromethane / 24 h / 20 °C / Inert atmosphere 3: hydrogenchloride / water / 24 h / Reflux; Inert atmosphere
Multi-step reaction with 3 steps 1: (R)-2,2'-diphenyl-3,3'-biphenanthryl-4,4'-diyl phosphate / toluene / 96 h / 20 °C / Inert atmosphere 2: Phenylselenyl bromide; silver trifluoromethanesulfonate / dichloromethane / 24 h / 20 °C / Inert atmosphere 3: hydrogenchloride / water / 24 h / Reflux; Inert atmosphere
  • 8
  • [ 1334404-90-8 ]
  • [ 200352-28-9 ]
YieldReaction ConditionsOperation in experiment
100% With hydrogenchloride In water for 24h; Reflux; Inert atmosphere;
  • 9
  • [ 796600-15-2 ]
  • cis-2-amino-cyclohexanol hydrochloride [ No CAS ]
  • [ 1430231-24-5 ]
YieldReaction ConditionsOperation in experiment
29% With N-ethyl-N,N-diisopropylamine; at 180 - 190℃; for 6h;Microwave irradiation; Example 242-Chloro-4-[[(lR,2S)-2-hydroxycyclohexyl]amino]-3-methyl-benzonitrileA mixture of <strong>[796600-15-2]2-chloro-4-fluoro-3-methyl-benzonitrile</strong> (500 mg, 2.95 mmol), diisopropylethylamine (1.29 mL, 7.37 mmol), and (lS,2R)-2-aminocyclohexanol hydrochloride (670 mg, 4.42 mmol, Acros) is microwaved using a CEM microwave at 190 C for 2 h and 180 C for 4 h. The mixture is diluted with dichloromethane and washed with 1 N HCl. The aqueous layer is extracted again with dichloromethane. The combined organic phases are dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting residue is purified using radial chromatography, eluting with 2%methanol/dichloromethane. The isolated product is recrystallized with ether and hexane to yield the title compound as a white solid (231 mg, 29%). LC-ES/MS m/z 265.0 (M+1).The compounds in Table 8 below are prepared by essentially following the procedure described in Example 24, using the appropriate chiral amino-alcohol (commercially available) and <strong>[796600-15-2]2-chloro-4-fluoro-3-methyl-benzonitrile</strong>.
  • 10
  • [ 200352-28-9 ]
  • [ 10027-87-9 ]
YieldReaction ConditionsOperation in experiment
300 mg With dmap; sodium azide; trifluoromethylsulfonic anhydride In dichloromethane at 20℃; 7 Sodium azide (2.43 g, 18.7 mmol) was dissolved in 7.6 mL water and stirred in ice bath. To it were added 8 mL DCM and then Tf20 (1.28 mL, 7.6 mmol).The mixture was stirred for 3 h in ice bath. The DCM phase was separated, and the aqueous phase was extracted with DCM twice. The combined DCM phase was washed with sat. NaHC03 and water, dried over MgS04. (lS,2R)-2-Aminocyclohexanol hydrochloride (302 mg, 2.0 mmol) was dissolved in 5 mL dry DCM and stirred at RT. To it were added DMAP (1.07 g, 8.8 mmol) and then the above- prepared TfN3/T)CM solution dropwise. The mixture was stirred for overnight. It was concentrated in vacuo and subjected to flash column to isolate (lS,2R)-2-azidocyclohexanol (300 mg, a clear oil). Proton NMR: (CDC13) δ 3.74 (1H, m), 3.59 (1H, m), 2.72 (1H, s), 1.83 (1H, m), 1.69-1.48 (5H, m), 1.27 (2H, m) ppm.
  • 11
  • [ 1018782-76-7 ]
  • [ 200352-28-9 ]
  • [ 1493777-56-2 ]
YieldReaction ConditionsOperation in experiment
95% Stage #1: 5-(4-chlorophenyl)-6-(cyclopropylmethoxy)-3-pyridinecarboxylic acid With 1-chloro-1-(dimethylamino)-2-methyl-1-propene In dichloromethane at 20℃; for 0.5h; Inert atmosphere; Stage #2: cis-2-amino-cyclohexanol hydrochloride With N-ethyl-N,N-diisopropylamine In dichloromethane; N,N-dimethyl-formamide at 20℃; for 1h; Inert atmosphere;
  • 12
  • [ 500860-54-8 ]
  • [ 200352-28-9 ]
  • [ 2060003-74-7 ]
YieldReaction ConditionsOperation in experiment
68% In butan-1-ol 80.a (a) (1 S,2R)-2-(6-Chloro-4, 8-bis(methylamino)pyrimido[5 ,4-dj pyrimidin-2-ylamino) cyclohexanol (134) 2,6-Dichloro-N,N’ -dimethyl-pyrimido [5 ,4-djpyrimidine-4, 8-diamine (88) (250 mg, 0.96 mmol) and (1S,2R)-2-aminocyclohexanol hydrochloride were reacted in n-butanol to afford (1 S,2R)-2-(6-chloro-4, 8-bis(methylamino)pyrimido [5 ,4-dj pyrimidin-2-ylamino) cyclohexanol (134) (221 mg, 68% yield). 300 MHz ‘H NMR (CDC13, ppm): 6.64-6.50 (2H, m) 5.20 (1H, d, J=7.3 Hz) 4.19-4.09 (1H, m) 4.05-3.98 (1H, m) 3.3-3.0 (1H, br s) 3.14 (3H,d, J=5.2 Hz) 3.05 (3H, d, J5.1 Hz) 1.84-1.36 (8H, m). ESI-MS (m/z): 338, 340 [M+Hf’.
  • 13
  • [ 108-24-7 ]
  • [ 200352-28-9 ]
  • [ 18421-16-4 ]
YieldReaction ConditionsOperation in experiment
100% Stage #1: cis-2-amino-cyclohexanol hydrochloride With sodium carbonate In acetone at 0℃; Stage #2: acetic anhydride In acetone at 0 - 20℃; for 3h;
  • 14
  • [ 200352-28-9 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: sodium carbonate / acetone / 0 °C 1.2: 3 h / 0 - 20 °C 2.1: Dess-Martin periodane / dichloromethane / 3 h / 20 °C
 

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