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Chemical Structure| 190792-72-4 Chemical Structure| 190792-72-4

Structure of 190792-72-4

Chemical Structure| 190792-72-4

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Product Details of [ 190792-72-4 ]

CAS No. :190792-72-4
Formula : C6H14ClNO
M.W : 151.63
SMILES Code : Cl.N[C@H]1CCCC[C@H]1O
English Name :(1R,2S)-2-Aminocyclohexanol hydrochloride
MDL No. :MFCD11618002
InChI Key :LKKCSUHCVGCGFA-RIHPBJNCSA-N
Pubchem ID :12228413

Safety of [ 190792-72-4 ]

Computational Chemistry of [ 190792-72-4 ] 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 [ 190792-72-4 ]

* 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 [ 190792-72-4 ]

[ 190792-72-4 ] Synthesis Path-Downstream   1~10

  • 1
  • [ 190848-36-3 ]
  • [ 190792-72-4 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; thionyl chloride 1) CHCl3, 0 deg C --> rt, 1 h, rt, 2 h; 2) reflux, 1 h; Yield given. Multistep reaction;
  • 2
  • [ 832099-55-5 ]
  • [ 190792-72-4 ]
  • [ 837377-71-6 ]
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; 32 Example 32; 5-Fluoro-N-(1S,2R-2-hydroxy-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. 627MMOL), (1R, 2S)-2-AMINO-CYCLOHEXAN-1-OL HYDROCHLORIDE (100mg, 0. 627MOL), 1-HYDROXYBENZOTRIAZOLE (95MG, 0. 704MOL) and triethylamine (350µl, 2. 51mmol) in DIMETHYLFORMAMIDE (5ML) under nitrogen at room temperature. The reaction was stirred for 18h and partitioned between DIETHYLETHER (60M1) and water (60ml). The organic phase was removed and washed with water (30MOI), 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- (1 S, 2R-2-HYDROXY-ACETYL-CYCLOHEXYL)-2- (3-METHYLSULFANYL- phenoxy) -nicotinamide (40mg) as an oil. 1H NMR (400MHZ, CDCI3) : (5= 8. 25-8.39 (2H, d + dd), 8.03-8. 05 (1H, d), 7.29-7. 38 (1H, t), 7.10-7. 18 (1H, d), 7.04 (1H, s), 6.92-6. 97 (1H, d), 4.17-4. 23 (1H, m), 3.98- 4.03 (1H, brs), 2.46 (3H, s), 2.04-2. 17 (1H, brs), 1.52-1. 80 (6H, 2xm), 1.38-1. 50 (2H, m) ppm. LRMS (electrospray) : M/Z [M+H] + 377, [M+NA] + 399, [M-H] + 375. Anal. Found C, 59.26 ; H, 5.57 ; N, 7.16. C19H21FN2O3S. 0. 4mol H20 requires C, 59.48 ; H, 5.73 ; N, 7.30%.
  • 3
  • [ 947274-13-7 ]
  • [ 190792-72-4 ]
  • [ 1084793-49-6 ]
YieldReaction ConditionsOperation in experiment
With triethylamine In N,N-dimethyl-formamide at 0 - 20℃; for 12h; 15 (IR, 2S) -2-Aminocyclohexanol hydrochloride (5.3 g) and triethylamine (15.1 ml) were dissolved in DMF (100 ml), and the solution was ice-cooled. Ethyl 3-bromo-2-isocyano-3- phenylacrylate (9.8 g) was added, and the mixture was stirred at room temperature for 12 hr. The reaction mixture was concentrated under reduced pressure, and partitioned between ethyl acetate and water. The organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, and the fraction eluted with ethyl acetate-methanol (9:1) was concentrated under reduced pressure to give the object compound (6.13 g) .1H-NMR (CDCl3) δ 1.10 (3H, t) , 1.21-1.37 (2H, m) , 1.38-1.52 (1H, m) , 1.60-1.79 (2H, m) , 1.80-1.97 (2H, m) , 2.22-2.37 (2H, m) , 3.76 (1H, dt), 4.04 (1H, br s) , 4.13 (2H, q) , 7.20-7.31 (2H, m) ,7.39-7.51 (3H, m) , 7.86 (1H, s)
  • 4
  • [ 796600-15-2 ]
  • (1R,2S)-2-aminocyclohexanol hydrochloride [ No CAS ]
  • [ 1430231-28-9 ]
YieldReaction ConditionsOperation in experiment
68% With sodium hydrogencarbonate; In water; dimethyl sulfoxide; at 130℃; for 48h; Example 282-Chloro-4-[[(lS,2R)-2-hydroxycyclohexyl] amino] -3 -methyl-benzonitrileA solution of 2-chloro-4-fluoro-3 -methyl-benzonitrile (500 mg, 2.95 mmol), (1R,2S)- 2-aminocyclohexanol hydrochloride (671 mg, 4.42 mmol, Small Molecules, Inc.) and sodium bicarbonate (991 mg, 11.8 mmol) in DMSO (14.7 mL), and water (2.1 mL) is heated at 130 C for 48 h. After cooling to room temperature, the mixture is diluted with 1 N HCl and extracted twice with EtOAc. The organic layers are combined, dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting residue is purified using radialchromatography, eluting with 2% methanol/dichloromethane to furnish the title compound as an off-white solid (527 mg, 68%). LC-ES/MS m/z 265.2 (M+l).
  • 5
  • [ 1610679-57-6 ]
  • [ 190792-72-4 ]
  • [ 1610679-85-0 ]
YieldReaction ConditionsOperation in experiment
97% With N-ethyl-N,N-diisopropylamine at 20℃; for 24h; General Method C (nucleophilic substitutions of amines) To a solution of pyrazolo[l,5-a]pyrimidin-5-chlorine derivative (1 equiv) or 2- (methylsulfonyl)-8-arylpyrazolo[ 1,5-al [1,3 ,5ltriazin-4-amine (1.0 equiv) in THF, dioxane, DME, DMF or NMP was added amines or amine-HC1 (1-2 equiv) and DIPEA (1-3 equiv). The resulting mixture was stirred at rt for 24 h or more generally the reaction was heated in amicrowave reactor, an oil bath or a reaction block at temperatures from 35-130 °C for 2- 12 h. Solvent was removed in vacuo and the crude product was purified by flash chromatography.
97% With N-ethyl-N,N-diisopropylamine
  • 6
  • [ 1414772-61-4 ]
  • [ 190792-72-4 ]
  • [ 1610454-09-5 ]
YieldReaction ConditionsOperation in experiment
10% With N-ethyl-N,N-diisopropylamine In butan-1-ol at 150℃; for 72h; 5 (1R,2S)-2-[3-(1-Benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]amino}cyclohexanol 150 mg (0.56 mmol) 3-(1-benzofur-2-yl)-6-chloroimidazo[1,2-b]pyridazine and 168.7 mg (1.11 mmol) (1R,2S)-2-aminocyclohexanol hydrochloride (1:1) and 0.48 mL (2.78 mmol) N-ethyl-N-isopropylpropan-2-amine in 5.0 mL butan-1-ol were stirred 72 h at150°C. The solvent was removed. The residue was purified by HPLC to yield 19 mg (10%) product. LC-MS (Method 2): Rt = 1.08 min; MS (ESIpos) m/z = 349 [M+H]+. 1H-NMR (600 MHz ,DMSO-d6), δ [ppm]= 1.40-1.52 (2H), 1.63-1.87 (6H), 3.88-3.94 (1H), 4.13-4.17 (1H), 4.70-4.74 (1H), 6.95-7.02 (2H), 7.27-7.31 (1H), 7.32-7.36 (1H), 7.52-7.54 (1H), 7.62-7.66 (1H), 7.68-7.72 (1H), 7.80-7.84 (1H), 7.93 (1H).
  • 7
  • [ 1610679-66-7 ]
  • [ 190792-72-4 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
79% With N-ethyl-N,N-diisopropylamine In 1-methyl-pyrrolidin-2-one at 130℃; for 3h; Sealed tube; Microwave irradiation; tert-butyl ( 3-bromo-5-( f(lS, 2R)-2-hvdroxycvclohexyl)amino)pyrazolo[l .5-a Jpyrimidin- 7-yl) ( yclopropylmethyQcarbamate To a solution of using tert-butyl (3-bromo-5-chloropyrazolo[l,5- a]pyrimidin-7-yl)(cyclopropylmethyl)carbamate (9.0 g, 22.5 mmol) in NMP (90 mL) was added (lR,2S)-2- aminocyclohexanol HCl (4.08 g, 27.0 mmol), and DIPEA (3.47 g, 25.1 mmol). The reaction was divided and sealed into six microwave vials. Each vial was microwaved for 3 h at 130 °C. Water and EtO Ac were added to separate the phases and the aqueous phase was extracted with EtO Ac. The combined organic extracts were dried over Na2S04, filtered and concentrated. The crude product was purified by flash chromatography (gradient: EtO Ac/hex 0-50%) using three columns in parallel to give the title compound as a beige solid (8.51 g, 79%). i NMR (400 MHz, CDCl3) δ ppm 7.80 (s, 1H), 6.08 (s, 1H), 5.33-5.19 (m, 1H), 4.26-4.14 (m, 1H), 4.13-4.06 (m, 1H), 3.61 (d, J = 7.3 Hz, 2H), 2.51 (br. s, 1H), 1.89-1.62 (m, 8H), 1.55-1.45 (m, 2H), 1.40 (s, 9H), 1.06-0.95 (m, 1H), 0.47-0.38 (m, 2H), 0.17-0.07 (m, 2H); MS ESI [M + H]+ 408.3, calcd for [C2iH3oBrN503 + H]+ 480.2.
79% With N-ethyl-N,N-diisopropylamine
  • 8
  • [ 500860-54-8 ]
  • [ 190792-72-4 ]
  • [ 2060003-68-9 ]
YieldReaction ConditionsOperation in experiment
43% With N-ethyl-N,N-diisopropylamine In butan-1-ol at 110℃; for 100h; 78.a (a) (1 R,2S)-2-(6-Chloro-4, 8-bis(methylamino)pyrimido[5 ,4-dj pyrimidin-2-ylamino) cyclohexanol (130) A mixture of 2,6-dichloro-N,N ‘ -dimethyl-pyrimido [5 ,4-dj pyrimidine-4, 8- diamine (88) (250 mg, 0.96 mmol), (1R,2S)-2-aminocyclohexanol hydrochloride (146 mg, 0.96 mmol) and N,N-diisopropylethylamine (319 tL, 1.92 mmol) in n-butanol (4 mL) washeated at 110°C for lOOh. The mixture was cooled, and a saturated NaHCO3 solution (20 mL) was added. The resulting suspension was extracted with EtOAc (3 x 3OmL). The combined organic extracts were washed with a brine solution (50 mL) and dried over solide anhydrous Na2SO4. The solvent was removed and the residue was purified by flash column chromatography using gradient elution from PE / EtOAc (9/1) to PE / EtOAc (1/99) to afford (1 R,2S)-2-(6-chloro-4,8-bis(methylamino)pyrimido[5,4-djpyrimidin-2-ylamrno)cyclohexanol (130)(140 mg, 43% yield). 300 MHz ‘H NMR (CDC13, ppm): 6.63-6.52 (2H, m) 5.20 (1H, d, J7.1 Hz) 4.19-4.08 (1H, m) 4.06-3.98 (1H, m) 3.3-3.0 (1H, br s) 3.14 (3H, d, J=5.2 Hz) 3.05(3H, d, J=5.1 Hz) 1.84-1.57 (6H, m) 1.57-1.36 (2H, m). ESI-MS (m/z): 338, 340 [M+Hf’.
  • 9
  • [ 2162986-17-4 ]
  • [ 190792-72-4 ]
  • [ 2162982-89-8 ]
YieldReaction ConditionsOperation in experiment
49 mg With dmap; N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 14h; 103 6-(4-Chlorophenyl)-2-(3-fluorophenyl)-N-(cis-2-hydroxycyclohexyl)-3-oxo-2,3- dihydropyridazine-4-carboxamide A solution of 75 mg intermediate 17, 66 mg cis-2-amino-cyclohexanol hydrochloride (1 :1 ), 165 mg HATU, 0.1 1 mL ethyldiisopropylamine and 1 .3 mg 4-dimethylaminopyridine in 2 mL of DMF was stirred at room temperature for 14 hours. Then the reaction mixture was filtered and subjected to RP-HPLC (Instrument: Waters Autopurification MS SingleQuad; Column: Waters XBrigde C18 5μ 100x30mm; eluent A: water + 0.1 vol % formic acid (99%), eluent B: acetonitrile; gradient: 0-5.5 min 5-100% B; flow 70 mL/min; temperature: 25 °C; DAD scan: 210-400 nm) to yield 49 mg 6-(4-chlorophenyl)-2-(3-fluorophenyl)-N-(cis-2-hydroxycyclohexyl)- 3-0X0-2, 3-dihydropyridazine-4-carboxamide. 1H NMR (400 MHz, DMSO-d6) δ ppm = 1.33 (m, 2 H), 1.46 - 1 .71 (m, 6 H), 3.77 (m, 1 H), 3.87 - 3.96 (m, 1 H), 4.87 (d, 1 H), 7.39 (tdd, 1 H), 7.51 - 7.66 (m, 5 H), 7.95 - 8.03 (m, 2 H), 8.66 (s, 1 H), 9.64 (d, 1 H).
  • 10
  • [ 2162986-36-7 ]
  • [ 190792-72-4 ]
  • [ 2162982-92-3 ]
YieldReaction ConditionsOperation in experiment
41 mg With dmap; N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 14h; 106 2-(3-Fluorophenyl)-N-(cis-2-hydroxycyclohexyl)-6-(4-methoxyphenyl)-3-oxo-2,3- dihydropyridazine-4-carboxamide A solution of 100 mg intermediate 2-(3-fluorophenyl)-6-(4-methoxyphenyl)-3-oxo-2,3- dihydropyridazine-4-carboxylic acid, 82 mg cis-2-amino-cyclohexanol hydrochloride (1 :1 ), 201 mg HATU, 0.14 mL ethyldiisopropylamine and 1 .6 mg 4-dimethylaminopyridine in 2 mL of DMF was stirred at room temperature for 14 hours. Then the reaction mixture was filtered and subjected to RP-HPLC (Instrument: Waters Autopurification MS SingleQuad; Column: Waters XBrigde C18 5μ 100x30mm; eluent A: water + 0.1 vol % formic acid (99%), eluent B: acetonitrile; gradient: 0-5.5 min 5-100% B; flow 70 mL/min; temperature: 25 °C; DAD scan: 210-400 nm) to yield 41 mg 2-(3-fluorophenyl)-N-(cis-2-hydroxycyclohexyl)-6-(4- methoxyphenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide. 1H NMR (400 MHz, DMSO-d6) δ ppm = 1.32 (m, 2 H), 1.48 - 1 .70 (m, 6 H), 3.77 (m, 1 H), 3.82 (s, 3 H), 3.91 (m, 1 H), 4.86 (d, 1 H), 7.04 - 7.1 1 (m, 2 H), 7.34 - 7.42 (m, 1 H), 7.50 - 7.56 (m, 1 H), 7.56 - 7.66 (m, 2 H), 7.87 - 7.93 (m, 2 H), 8.62 (s, 1 H), 9.69 (d, 1 H).
 

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