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Chemical Structure| 2095772-93-1 Chemical Structure| 2095772-93-1

Structure of 2095772-93-1

Chemical Structure| 2095772-93-1

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Product Details of [ 2095772-93-1 ]

CAS No. :2095772-93-1
Formula : C9H14ClNO
M.W : 187.67
SMILES Code : CC1=CC([C@H](N)CO)=CC=C1.[H]Cl
English Name :(S)-2-Amino-2-(m-tolyl)ethanol hydrochloride
MDL No. :MFCD12758125
InChI Key :IHNWJJLKSBXLRI-SBSPUUFOSA-N
Pubchem ID :122404766

Safety of [ 2095772-93-1 ]

Computational Chemistry of [ 2095772-93-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.33
Num. rotatable bonds 2
Num. H-bond acceptors 2.0
Num. H-bond donors 2.0
Molar Refractivity 52.02
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

1.3
Log Po/w (WLOGP)?

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

1.46
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.

1.56
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

1.16

Water Solubility

Log S (ESOL):?

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

-2.06
Solubility 1.63 mg/ml ; 0.0087 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.

-1.87
Solubility 2.52 mg/ml ; 0.0134 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

-2.29
Solubility 0.971 mg/ml ; 0.00518 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

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)

1.54

Application In Synthesis of [ 2095772-93-1 ]

* 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 [ 2095772-93-1 ]

[ 2095772-93-1 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 2095725-66-7 ]
  • [ 2095772-93-1 ]
  • [ 2095719-79-0 ]
YieldReaction ConditionsOperation in experiment
27.4% With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine In N,N-dimethyl-formamide at 20℃; 672 Example 672: (2R)-2-[6-(5-chloro-2-[(2S)-1-hydroxypropan-2-yl]amino}pyrimidin-4-yl)-4- fluoro-1 -oxo-2,3-dihydro-1 H-isoindol-2-yl]-N-[(1S)-2-hydroxy-1-(3- methylphenyl)ethyl]propanamide Example 672: (2R)-2-[6-(5-chloro-2-[(2S)-1-hydroxypropan-2-yl]amino}pyrimidin-4-yl)-4- fluoro-1 -oxo-2,3-dihydro-1 H-isoindol-2-yl]-N-[(1S)-2-hydroxy-1-(3- methylphenyl)ethyl]propanamide (3606) A stirred solution of (S)-2-amino-2-(m-tolyl)ethanol, HCI (32 mg, 0.171 mmol), (R)-2-(6-(5- chloro-2-(((S)-1-hydroxypropan-2-yl)amino)pyrimidin-4-yl)-4-fluoro-1-oxoisoindolin-2- yl)propanoic acid (91 mg, 0.140 mmol) and triethylamine (78 μΙ, 0.561 mmol) in DMF (2 ml) was treated with TBTU (50 mg, 0.156 mmol) and stirred at room temperature overnight. The mixture was diluted with ethyl acetate (10 ml), was washed successively with 1 M KHSO4 (5 ml), NaHCC (5 ml), brine (2x 5 ml), water (4x 5 ml), then dried (MgSCU) and evaporated. The residue was purified on a 12 g graceresolv silica cartridge, using a gradient of 0 to 5% of ethanol in ethyl acetate as a eluent to give a colourless glass which was further purified by reversed phase preparative HPLC ( Waters XSelect CSH C18 OBD, 130A, 5 pm, 19 mm X 50 mm column, using a gradient of 20 to 50% of acetonitrile in water with 0.1 % formic acid in both at 28 ml/min as eluent). The clean fractions were pooled and concentrated to remove most of the acetonitrile. The residue was freeze-dried to the title compound (21 mg, 27.4 %) as a fluffy white solid. 1 H NMR (DMSO-d6, 400 MHz) δ 8.56 (1 H, d), 8.45 (1 H, s), 7.97 - 7.88 (1 H, m), 7.83 (1 H, d), 7.34 (1 H, s), 7.20 (1 H, t), 7.13 - 7.00 (3H, m), 4.98 (1 H, q), 4.89 (1 H, t), 4.85 - 4.76 (2H, m), 4.74 - 4.67 (2H, m), 4.05 - 3.90 (1 H, m), 3.59 - 3.41 (3H, m), 2.29 (3H, s), 1.44 (3H, d), 1.13 (3H, d). (One proton was not observed and overlapped with water peak). LCMS: [M+H]+ = 542.
  • 2
  • [ 2095665-46-4 ]
  • [ 2095772-93-1 ]
  • [ 2095719-90-5 ]
YieldReaction ConditionsOperation in experiment
68% Stage #1: (2R)-2-(6-{5-chloro-2-[(oxan-4-yl)amino]pyrimidin-4-yl}-1-oxo-2,3-dihyro-1H-isoindol-2-yl)propanoic acid; (2S)-2-amino-2-(3-methylphenyl)ethan-1-ol hydrochloride With triethylamine In N,N-dimethyl-formamide for 0.25h; Stage #2: With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate In N,N-dimethyl-formamide at 20℃; for 2h; 683.B Example 683: (2R)-2-(6-{5-chloro-2-[(oxan-4-yl)amino]pyrimidin-4-yl}-1-oxo-2,3-dihydro- 1 H-isoindol-2-yl)-N-[(1 S)-2-hydroxy-1 -(3-methylphenyl)ethyl]propanamide Method B: triethylamine (2.060 mL, 14.78 mmol) was added to a suspension of (R)-2-(6-(5- chloro-2-((oxan-4-yl)amino)pyrimidin-4-yl)-1-oxoisoindolin-2-yl)propanoic acid (1.54 g, 3.69 mmol) and (S)-2-amino-2-(m-tolyl)ethanol hydrochloride (0.763 g, 4.06 mmol) in DMF (15 mL, 194 mmol). After 15 minutes, TBTU (1.305 g, 4.06 mmol) was added and the mixture was stirred for 2 h at room temperature. The reaction was diluted with EtOAc (30 mL) and water (100 mL). The phases were separated and the aqueous phase was extracted with EtOAc (2x30 mL). The combined organic extracts were washed with NH4CI (100 mL), NaHC03 (100 mL), brine (2x100 mL), dried (MgS04) and concentrated. The crude product was purified by chromatography (S1O2, 40 g column, 0-7% MeOH in DCM) to afford the product as a colourless gum. The gum was triturated with diethyl ether (100 mL) to give the title compound (1.409 g, 68.0 %) as a white solid. 1 H NMR (DMSO, 400 MHz) δ 8.56 (1 H, d), 8.45 (1 H, s), 8.08 - 8.02 (1 H, m), 7.98 (1 H, dd), 7.75 (1 H, d), 7.63 (1 H, s), 7.21 (1 H, t), 7.13 - 6.96 (3H, m), 5.01 (1 H, q), 4.93 - 4.84 (1 H, m), 4.83 - 4.72 (2H, m), 4.60 (1 H, d), 4.01 - 3.80 (3H, m), 3.59 - 3.50 (2H, m), 3.43 - 3.36 (2H, m), 2.30 (3H, s), 1.90 - 1.79 (2H, m), 1.60 - 1.46 (2H, m), 1.43 (3H, d). LCMS: [M+H]+ = 550
 

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