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Structure of 99799-09-4

Chemical Structure| 99799-09-4

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Product Details of [ 99799-09-4 ]

CAS No. :99799-09-4
Formula : C8H14O3
M.W : 158.20
SMILES Code : O=C(O)CC1CCC(O)CC1
MDL No. :MFCD13659403
InChI Key :ALTAAUJNHYWOGS-UHFFFAOYSA-N
Pubchem ID :12702257

Safety of [ 99799-09-4 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319
Precautionary Statements:P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313

Computational Chemistry of [ 99799-09-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 0
Fraction Csp3 0.88
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 41.39
TPSA ?

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

57.53 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.35
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

0.57
Log Po/w (WLOGP)?

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

1.01
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.

0.69
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

0.74
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.87

Water Solubility

Log S (ESOL):?

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

-1.05
Solubility 14.2 mg/ml ; 0.0896 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.

-1.35
Solubility 7.05 mg/ml ; 0.0446 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

-0.28
Solubility 83.6 mg/ml ; 0.528 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.

-6.86 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.

0.56

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)

2.25

Application In Synthesis of [ 99799-09-4 ]

* 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 [ 99799-09-4 ]

[ 99799-09-4 ] Synthesis Path-Downstream   1~13

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  • [ 102942-99-4 ]
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  • [ 554411-25-5 ]
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  • [ 798533-31-0 ]
YieldReaction ConditionsOperation in experiment
25% EXAMPLE 50 (trans)-2-(4-Hydroxy-cyclohexyl)-N-[4-methoxy-7-(tetrahydro-pyran-4-yl)-benzothiazol-2-yl]-acetamide Using 4-methoxy-7-(tetrahydro-pyran-4-yl)-benzothiazol-2-ylamine and <strong>[99799-09-4](4-hydroxy-cyclohexyl)-acetic acid</strong>, the title compound was prepared in the same manner as described for N-[4-methoxy-7-(tetrahydro-pyran-4-yl)-benzothiazol-2-yl]-2-(tetrahydro-pyran-4-yl)-acetamide and obtained as white crystals (25% yield). Mp 120-145 C., MS: m/e=405(M+H+).
  • 8
  • [ 14199-15-6 ]
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  • 9
  • [ 99183-13-8 ]
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YieldReaction ConditionsOperation in experiment
150 mg With potassium hydroxide; In methanol; water; at 60.0℃; for 6.0h; A mixture of potassium hydroxide (326 mg) and methyl 2-(4-hydroxycyclohexyl)acetate (D8, 500 mg) in methanol (20 mL) and water (20 mL) was stirred at 60C for 6 hours. After cooling to RT, the reaction mixture was concentrated and acidified with HC1 solution (2 M) to adjust the pH valute to 1, and then extracted with EA (50 mL). The organic layer was dried over Na2 SO4, filtered and concentrated in vacuo to afford the title compound (150 mg) as white solid. MS (ESI): C8H,403requires 158; found 159 [M+HJ.
3 g With water; potassium hydroxide; In methanol; at 80.0℃; for 6.0h; Description 32-(4-Hydroxycyclohexyl)acetic acid (D3) The mixture of potassium hydroxide (2.61 g) and methyl 2-(4-hydroxycyclohexyl)acetate (D2, 4 g) was dissloved in MeOH (30 mL) and water (30 mL). The reaction mixture was stirred for 6 hours at 80C. The reaction mixture was concentrated and acidified with 2 M HC1 (aq.) to pH = 1, then extrated with DCM (2x50 mL). The organic layer was dried with anhydrous sodium sulfate.Filtered, the filtrate was concentrated to afford the title compound (3 g) as yellow solid. MS (ESI):C8H1403 requires 158; found 157 [IVI-H].
  • 10
  • [ 99799-09-4 ]
  • (S)-(4-(3-amino-5-chloro-2-methylbenzyl)-2-methylpiperazin-1-yl)(cyclopentyl)methanone [ No CAS ]
  • N-(5-chloro-3-(((S)-4-(cyclopentanecarbonyl)-3-methylpiperazin-1-yl)methyl)-2-methylphenyl)-2-((1s,4R)-4-hydroxycyclohexyl)acetamide [ No CAS ]
  • N-(5-chloro-3-(((S)-4-(cyclopentanecarbonyl)-3-methylpiperazin-1-yl)methyl)-2-methylphenyl)-2-((1r,4S)-4-hydroxycyclohexyl)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
48 mg; 18 mg With HATU; In N,N-dimethyl-formamide; at 20.0℃; for 6.0h; Examples 61&62N-(5-chloro-3-(((S)-4-(cyclopentanecarbonyl)-3-methylpiperazin-1-yl)methyl)-2-methylphenyl)-2-((ls,4R)-4-hydroxycyclohexyl)acetamide & N-(5-chloro-3-(((S)-4-(cyclopentanecarbonyl)-3-methylpiperazin-1-yl)methyl)-2-methylphenyl)-2-((lr,4S)-4- hydroxycyclohexyl)acetamide (E61 & E62) 2-(4-Hydroxycyclohexyl)acetic acid (D3, 150 mg) and HATU (361 mg) were added to the (S)-(4-(3-amino-5-chloro-2-methylbenzyl)-2-methylpiperazin-1 -yl)(cyclopentyl)methanone (D157, 332mg) solution in DMF (20 mL), the reaction mixture was continued to stir for 6 hours at RT. Water(20 mL) was added and extracted with EtOAc (50 mL), the organic layer was dried over Na2SO4.Filtered, the filtrated was concentrated and the residue was purified by preparative HPLC to affordthe two compounds (48 mg and 18 mg) as white solid. Isomer 1: ?H NMR (500 MHz, DMSO-d6):9.35 (s, 111), 7.38 (s, 1H), 7.15 (s, 1H), 4.54 (brs, 0.5H), 4.47 (d, J= 4.4 Hz, 1H), 4.19 (d, J 10.1 Hz, 1H), 3.75 (d, J= 12.9 Hz, 0.511), 3.45-3.36 (m, 2ff), 3.36-3.33 (m, 1ff), 3.17 (t, J 12.1 Hz, 0.5H), 2.97-2.86 (m, 1H), 2.81-2.68 (m, 1.511), 2.60 (d, J= 9.5 Hz, 111), 2.21 (d, J= 6.9 Hz, 2H),2.16 (s, 3H), 2.14-1.45 (m, 15H), 1.29-0.95 (m, 7H). MS (ESI): C27H.40C1N3O3 requires 489; found490 [M+H]. Isomer 2: ?H NMR (500 MHz, DMSO-d6): 9.37 (s, 1H), 7.38 (d, J= 1.6 Hz, 1H),7.15 (s, 1H), 4.54 (brs, 0.511), 4.30 (d, J- 3.2 Hz, 1H), 4.20 (d, J= 8.5 Hz, 1H), 3.79-3.70 (m,1.5H), 3.46-3.36 (m, 211), 3.18 (t, J 11.7 Hz, 0.5H), 2.91 (quin, J=? 7.4 Hz, 1H), 2.81-2.68 (m,1.5H), 2.65-2.57 (m, 1H), 2.26 (d,J 7.3 Hz, 2H), 2.17 (s, 311), 2.13-1.38 (m, 19H), 1.27-1.05 (m,311). MS (ESI): C27H40C1N3O3 requires 489; found 490 {M+Hj.
  • 11
  • [ 99799-09-4 ]
  • (S)-4-(3-amino-5-chloro-2-methylbenzyl)-2-methylpiperazine-1-carboxylic acid tert-butyl ester [ No CAS ]
  • (S)-tertbutyl 4-(5-chloro-3-(2-(4-hydroxycyclohexyl)acetamido)-2-methylbenzyl)-2-methylpiperazine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With HATU; In N,N-dimethyl-formamide; at 20.0℃; for 18.0h; Description 204(S)-tert-butyl 4-(5-chloro-3-(5-fluoro-6-methylnicotinamido)-2-methylbenzyl)-2-methylpiperazine-1-carboxylate (D204)NHF N.0A solution of (S)-tert-butyl 4-(3 -amino-5-chloro-2-methylbenzyl)-2-methylpiperazine-1 -carboxylate (D159, 913 mg), 5-fluoro-6-methylnicotinic acid (Dl 13, 400 mg), HATU (980 mg)and DIPEA (0.45 0 mL) in DCM (100 mL) was stirred at RT for 18 hours. The mixture wasconcentrated under vacuum to afford the title compound (1.2 g) as red oil which was used directlyfor next step without further purification.
  • 12
  • [ 99799-09-4 ]
  • (S)-N-(5-chloro-2-methyl-3-((3-methylpiperazin-1-yl)methyl)phenyl)-2-(4-hydroxycyclohexyl)acetamide dihydrochloride [ No CAS ]
  • 13
  • [ 99799-09-4 ]
  • (S)-N-(5-chloro-3-((4-(2-cyclopropylacetyl)-3-methylpiperazin-1-yl)methyl)-2-methylphenyl)-2-(4-hydroxycyclohexyl)acetamide [ No CAS ]
  • (S)-N-(5-chloro-3-((4-(2-cyclopropylacetyl)-3-methylpiperazin-1-yl)methyl)-2-methylphenyl)-2-(4-hydroxycyclohexyl)acetamide [ No CAS ]
 

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Technical Information

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