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Chemical Structure| 851785-21-2 Chemical Structure| 851785-21-2

Structure of 851785-21-2

Chemical Structure| 851785-21-2

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Product Details of [ 851785-21-2 ]

CAS No. :851785-21-2
Formula : C11H16ClNO4S
M.W : 293.77
SMILES Code : O=C(OC)[C@@H](N)CC1=CC=CC(S(=O)(C)=O)=C1.[H]Cl
MDL No. :MFCD29037384
InChI Key :VUUYKOLKOIYVCR-PPHPATTJSA-N
Pubchem ID :91933723

Safety of [ 851785-21-2 ]

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

Computational Chemistry of [ 851785-21-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 18
Num. arom. heavy atoms 6
Fraction Csp3 0.36
Num. rotatable bonds 5
Num. H-bond acceptors 5.0
Num. H-bond donors 1.0
Molar Refractivity 69.88
TPSA ?

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

94.84 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

1.24
Log Po/w (WLOGP)?

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

2.02
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.

1.21
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

0.77
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.05

Water Solubility

Log S (ESOL):?

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

-2.36
Solubility 1.28 mg/ml ; 0.00437 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.

-2.83
Solubility 0.435 mg/ml ; 0.00148 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

-2.88
Solubility 0.383 mg/ml ; 0.0013 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

No
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.

-7.21 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<0.0
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)

2.61

Application In Synthesis of [ 851785-21-2 ]

* 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 [ 851785-21-2 ]

[ 851785-21-2 ] Synthesis Path-Downstream   1~8

  • 1
  • [ 851785-21-2 ]
  • [ 4659-45-4 ]
  • C18H17Cl2NO5S [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In dichloromethane; at 0 - 20℃; for 12.0h; EXAMPLE 16 [0322] This example describes the synthesis of which was prepared according to the procedure below. [0323] To a solution of 0.2 mmol of compound 8.4 (Example 8c or 8e) in 1 mmol of Et3N and 5 mL of dry CH2C12 was added 0.22 mmol of 2,6- dichlorobenzoyl chloride at 0C, the resulting mixture was stirred at room temperature for 12 hours. The solvent was removed and the residue was dried in vacuo. Subsequently, the residue was treated with 0. 8 mmol of LiOH-H20 in 2 mL of THF and 0.5 mL of H20. After stirring at room temperature for 30 minutes, the reaction mixture was added 1.0 mL of 1. ON aq. HC1. The organic solvent was removed, and the residue was diluted with 10 mL of brine. The mixture was extracted with EtOAc and the extract was dried with anhydrous Na2SO4. The solvent was removed and the residue was dried in vacuo to give the desired compound in 65% yield. 1H NMR (400 MHz, CD30D) 6 7.92 (s, 1 H), 7. 82 (d, J=6. 85 Hz, 1 H), 7.71 (d, J=6. 85 Hz, 1 H), 7.56 (t, J=7. 83 Hz, 1 H), 7.34 (m, 3 H), 5. 08 (dd, J=9. 78, 4.89 Hz, 1 H), 3.45 (dd, J=14. 67,4. 89 Hz, 1 H), 3.14 (dd, J=14. 67,9. 78 Hz, 1 H), 3.08 (s, 3 H) ppm; ESI-MS (m/z) : (M+H+) 416.00.
  • 2
  • C17H14Cl2N2O3 [ No CAS ]
  • [ 851785-21-2 ]
  • C28H27Cl2N3O6S [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; HATU; In DMF (N,N-dimethyl-formamide); at 20℃; for 14.0h; k) 1 equivalent of compound 18.10, 1 equivalent compound 8.4 (Example 8c or 8e), and 3 equivalents of DIEA were dissolved in DMF. 1.1 equivalent of HATU was added. The reaction was stirred at room temperature for 14 hours. The reaction mixture was diluted with ethyl acetate and washed with water, brine. The combined organics were dried with MgS04, filtered, and concentrated. The residue was then purified on silica gel column chromatography (gradient elution using ethyl acetate and hexanes) to provide pure intermediate ester. The ester was dissolved in methanol followed by addition of 2 equivalents of 1M LiOH (aq). Upon completion, the excess solvents were removed under reduced pressure and the resulting acid was then purified by reverse phase HPLC to give pure compound 18.
  • 3
  • C16H13Cl3O3 [ No CAS ]
  • [ 851785-21-2 ]
  • C27H26Cl3NO6S [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; HATU; In DMF (N,N-dimethyl-formamide); at 20℃; for 14.0h; f) 1 equivalent of compound 20.5, 1 equivalent of compound 8.4 (Example 8c or 8e), and 3 equivalents of DIEA were dissolved in DMF. 1.1 equivalent of HATU was added. The reaction was stirred at room temperature for 14 hours. The reaction mixture was diluted with ethyl acetate and washed with water, brine. The combined organics were dried with MgS04, filtered, and concentrated. The residue was then purified on silica gel column chromatography (gradient elution using ethyl acetate and hexanes) to provide pure compound 20.6.
  • 4
  • [ 851785-26-7 ]
  • [ 851785-21-2 ]
YieldReaction ConditionsOperation in experiment
98% With hydrogen;palladium on activated charcoal; In methanol; The compound 8.9 was hydrogenated (Pd/C, MeOH,) with a hydrogen balloon to afford compound 8.4 (yield 98%). ESI-MS (m/z) : (M+H+) 258.
  • 5
  • [ 67-56-1 ]
  • (S)-2-amino-3-(3-(methylsulfonyl)phenyl)propanoic acid [ No CAS ]
  • [ 851785-21-2 ]
YieldReaction ConditionsOperation in experiment
95% With thionyl chloride; at 0 - 20℃; 20 g of (S)-2-amino-3-(3-(methylsulfonyl)phenyl)propanoic acid was charged in 100 ml Methanol and reaction mass cooled to 0-5C. Thionyl chloride (12 g) was added drop wise below 10C and reaction mass was stirred at room temperature. After completion of reaction, solvents were distilled under vacuum followed by addition of isopropyl ether (100 ml) and filtered the solid to get 23 g of methyl (S)-2-amino-3-(3- (methylsulfonyl)phenyl)propanoate hydrochloride (Yield-95%)
  • 6
  • [ 851784-82-2 ]
  • [ 851785-21-2 ]
  • [ 851785-70-1 ]
YieldReaction ConditionsOperation in experiment
91.8% 2-(ieri-butoxycarbonyl)-5,7-dichloro- l,2,3,4-tetrahydroisoquinoline-6-carboxylic acid (20 g), HATU (27.5 g) was charged in DMF (60 ml) and diisopropyl ethylamine (22,2 g) was added. Reaction mass was cooled to 0-5C and added methyl (S)-2-amino-3-(3- (m.ethylsuIfonyl)phenyl)propanoate hydrochloride (17.6g) lot wise at 0-5C. Temperature of reaction mass was raised to room temperature. Stirred and reaction monitored by TLC. After completion of reaction, Water (100 ml) and MDC (100 ml) was added. Stirred and separated the layers. Organic layer washed with brine and 10% sodium carbonate solution. Organic layer distilled and charged 1 N HC1 (100 ml) to the residue. After complete hydrolysis pH of reaction mass was adjusted to 5.0-5.5 using sodium hydroxide solution. Reaction mass was filtered and solid so obtained was dried to get (S)-2-(5 ,7-dichloro- 1 ,2,3 ,4- tetrahydroisoquinoline-6-carb^ acid (25 g, (0185) 91.8% yield).
  • 7
  • [ 851784-82-2 ]
  • [ 851785-21-2 ]
  • tert-butyl (S)-5,7-dichloro-6-((1-methoxy-3-(3-(methylsulfonyl)phenyl)-1-oxopropan-2-yl)carbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
2-(ieri-butoxycarbonyl)-5,7-dichloro- l,2,3,4-tetrahydroisoquinoline-6-carboxylic acid (20.0g) was added to 50.0 ml of DMF followed by addition of DIPEA (37.2 g), HATU (27.4g) and stirred the reaction mass for 30 min at room temperature. Charged methyl (S)-2- amino-3-(3-(methylsulfonyl)phenyl)propanoate hydrochloride (17.6g) and stirred the reaction mass at 100C for 1-2 hrs. After completion of reaction, cooled the reaction mass to 30-35C, charged the reaction mass to the mixture of ethyl acetate (200ml) and water (200 ml) and stirred for 15-30 min at 30-35C. Separated the ethyl acetate and washed with acidic water (200ml water + 18ml of cone. HC1) followed by washing with water. Distilled the ethyl acetate at 40-45C to get tert-butyl (S)-5,7-dichloro-6-((l-methoxy-3-(3- (xnethylsulfonyl)phenyl)- l-oxopropan-2-yl)carbamoyl)-3,4-dihydro isoquinoline-2( lH)- carboxylate (40g, crude).
  • 8
  • [ 851785-21-2 ]
  • methyl (2S)-2-(2,6-dichloro-4-((((3-hydroxyphenyl)(methyl)phosphoryl)methyl)amino)benzamido)-3-(3-(methylsulfonyl)phenyl)propanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; Step D: methyl (2S)-2-(2,6-dichloro-4-((((3-hydroxyphenyl)(methyl)phosphoryl)methyl)amino)benzamido)-3-(3-(methylsulfonyl)phenyl)propanoate (Compound 29.4) Compound 11.4 was dissolved in DMF and <strong>[851785-21-2]methyl (2s)-2-amino-3-(3-(methylsulfonyl)phenyl)propionate hydrochloride</strong> (2 eq) was added, followed by DIPEA (10 eq) and HATU (2.5 eq). After stirring at normal temperature for 4 hours, 10 ml of dilute hydrochloric acid solution was added, and extracted with EA three times, and the organic phases were combined and spun-dried. Purification was made by reverse phase, and spun-dried under reduced pressure at 45 C. to obtain the target product.
 

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