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Chemical Structure| 99839-16-4 Chemical Structure| 99839-16-4

Structure of 99839-16-4

Chemical Structure| 99839-16-4

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Product Details of [ 99839-16-4 ]

CAS No. :99839-16-4
Formula : C6H9NOS
M.W : 143.21
SMILES Code : CC1=C(C)N=C(CO)S1
MDL No. :MFCD12198452
InChI Key :NNZZUYMCPDVPQA-UHFFFAOYSA-N
Pubchem ID :20402108

Safety of [ 99839-16-4 ]

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

Computational Chemistry of [ 99839-16-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 5
Fraction Csp3 0.5
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 38.17
TPSA ?

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

61.36 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.61
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

0.9
Log Po/w (WLOGP)?

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

1.1
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.

-0.09
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

2.75
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.25

Water Solubility

Log S (ESOL):?

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

-1.64
Solubility 3.28 mg/ml ; 0.0229 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.

-1.77
Solubility 2.41 mg/ml ; 0.0168 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

-1.87
Solubility 1.91 mg/ml ; 0.0134 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.

-6.53 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)

2.47

Application In Synthesis of [ 99839-16-4 ]

* 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 [ 99839-16-4 ]

[ 99839-16-4 ] Synthesis Path-Downstream   1~16

  • 1
  • [ 3581-91-7 ]
  • [ 591-51-5 ]
  • [ 99839-16-4 ]
  • 2
  • [ 29947-24-8 ]
  • [ 99839-16-4 ]
  • 4
  • [ 99839-16-4 ]
  • [ 533885-39-1 ]
  • 5
  • [ 533885-39-1 ]
  • [ 99839-16-4 ]
  • 6
  • [ 40516-65-2 ]
  • [ 4091-39-8 ]
  • [ 99839-16-4 ]
  • 8
  • [ 99839-16-4 ]
  • [ 1203605-21-3 ]
  • [ 1203604-45-8 ]
YieldReaction ConditionsOperation in experiment
38% Under argon, sodium hydride (60%, 3.1 mg, 0.08 mmol) was added to a solution of (4,5-dimethyl-1,3-thiazol-2-yl)methanol (16.2 mg, 0.11 mmol) in anhydrous THF (1 mL). The reaction mixture was stirred at room temperature for 20 minutes, then 3-chloro-5-(2,6-dimethoxyphenyl)-1,2,4-triazine (10 mg, 0.04 mmol, prepared as in example 41) was added and the resulting mixture was stirred overnight at 70C. An aqueous ammonium chloride solution was added and the mixture was extracted with diethyl ether and ethyl acetate. The combined organic extracts were dried over sodium sulfate, filtered and evaporated. Purification by preparative TLC (silica gel, dichloromethane/methanol 95/5) afforded 5-(2,6-dimethoxyphenyl)-3-[(4,5-dimethyl-1,3-thiazol-2-yl)methoxy]-1,2,4-triazine (5.4 mg, 38%) as a pale yellow oil. ESI-MS m/z 359 (M+H)+. 1H NMR (CDCl3), δ (ppm): 8.99 (s, 1H), 7.40 (t, J = 8.4 Hz, 1H), 6.64 (d, J = 8.4 Hz, 2H), 5.80 (s, 2H), 3.76 (s, 6H), 2.36 (s, 6H).
  • 9
  • [ 99839-16-4 ]
  • [ 124-63-0 ]
  • [ 1465782-82-4 ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In dichloromethane; at 0 - 20℃; for 1h; Step 3: Methanesulfonic acid 4,5-dimethyl-thiazol-2-ylmethyl ester To a stirred solution of (4,5-dimethyl-thiazol-2-yl)-methanol (200 mg, 1.4 mmol) and Et3N (478 mg, 4.2 mmol) in DCM (20 mL) was added MsCl (424 mL, 4.2 mmol) in dropwise at 0 C. After the additional, the mixture was stirred for 1 hour at room temperature. The reaction mixture was quenched by water (15 mL), extracted with DCM (3 x 10 mL). The combined organic phase was dried over Na2S04, filtered and concentrated in vacuum to give the crude product methanesulfonic acid 4,5-dimethyl-thiazol-2-ylmethyl eesstteerr (250 mg, 100% yield): lR NMR (400 MHz, CDC13) δ 5.21 (s, 2H), 3.67 (s, 3H), 2.88 (s, 6H).
  • 10
  • [ 74531-15-0 ]
  • [ 99839-16-4 ]
YieldReaction ConditionsOperation in experiment
2 g With methanol; sodium tetrahydroborate; at 40℃; Step 2: (4,5-Dimethyl-thiazol-2-yl)-methanol To a solution of 4,5-Dimethyl-thiazole (2.6 g, 18.4 mmol) in MeOH (40 mL) was added NaBH4 (1.4 g, 36.8 mmol) in portions while the temperature was below 40 C, and the mixture was stirred overnight. After TLC showed the start material was disappeared, the solvent was removed in vacuo. The residue was partitioned between water and ethyl acetate. The organic layer was washed with water and brine, dried over Na2S04j filtered and concentrated in vacuo to give the crude product, which was purified by column chromatography to give the pure product (4,5-dimethyl-thiazol-2-yl)-methanol (2 g, 77% yield): lR NMR (400 MHz, CDC13) δ 4.76 (s, 2H), 2.25-2.21 (m, 6H); ES-LCMS m/z 144.0 (M+H).
  • 11
  • [ 99839-16-4 ]
  • [ 1465782-34-6 ]
  • 12
  • [ 99839-16-4 ]
  • [ 1465783-05-4 ]
  • 13
  • [ 99839-16-4 ]
  • [ 1465782-35-7 ]
  • 14
  • [ 3581-91-7 ]
  • [ 99839-16-4 ]
  • 15
  • [ 99839-16-4 ]
  • (S)-isopropyl 2-(6-(bromomethyl)-4-(4,4-dimethylpiperidin-1-yl)-5-(4-(4-fluorophenethoxy)phenyl)-2-methylpyridin-3-yl)-2-(tert-butoxy)acetate [ No CAS ]
  • (S)-2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-6-(((4,5-dimethylthiazol-2-yl)methoxy)methyl)-5-(4-(4-fluorophenethoxy)phenyl)-2-methylpyridin-3-yl)acetic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
35.5% To a solution of<strong>[99839-16-4](4,5-dimethylthiazol-2-yl)methanol</strong> (20.95 mg, 0.146 mmol) in THF (1) at 0 C was added NaH (5.85 mg, 0.146 mmol) and the resulting mixture was stirred for 10 mi (S)-Isopropyl 2-(6-(bromomethyl)-4-(4,4-dimethylpiperidin-1-yl)-5-(4-(4- fluorophenethoxy)phenyl)-2-methylpyridin-3 -yl)-2-(tert-butoxy)acetate (50 mg, 0.073 mmol) in THF (0.5 mL) was then added and the mixture was stirred for 4 h. At this pointLCMS indicated completion of reaction. Mixture was then concentrated and treated with iON NaOH (0.073 mL, 0.731 mmol) in ethanol (1 mL) at 80 C for 4 h. Mixture was then cooled and purified by prep HPLC to afford (S)-2-(tert-butoxy)-2-(4-(4,4- dimethylpiperidin- 1 -yl)-6-(((4, 5 -dimethylthiazol-2-yl)methoxy)methyl)-5 -(4-(4- fluorophenethoxy)phenyl)-2-methylpyridin-3 -yl)acetic acid (18.3 mg, 0.026 mmol, 35.5% yield). ‘H NMR (500MHz, DMSO-d6) ö 7.43 - 7.32 (m, 2H), 7.23 (d, J=8.4 Hz, 1H),7.14 (t, J=8.8 Hz, 2H), 7.09 -6.98 (m, 2H), 6.94 (d, J=8.1 Hz, 1H), 5.82 (br. s., 1H), 4.54-4.35 (m, 2H), 4.30-4.15 (m, 3H), 4.12 (d, J=9.9 Hz, 1H), 3.05 (t, J=6.6 Hz, 2H), 2.85 -2.77 (m, 1H), 2.48 (s, 3H), 2.26 (s, 3H), 2.17 (s, 3H), 1.97- 1.87 (m, 1H), 1.50 (br. s.,1H), 1.38- 1.23 (m, 1H), 1.19(d,J12.iHz, 1H), 1.12(s,9H), 1.02(d,J11.7Hz, 1H),0.85 (br. s., 3H), 0.61 (br. s., 3H). LCMS (M+H) = 704.2.
  • 16
  • [ 99839-16-4 ]
  • 7-(tert-butyl)-2-(((4,5-dimethylthiazol-2-yl)methyl)thio)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-amine [ No CAS ]
 

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Technical Information

Categories

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[ 99839-16-4 ]

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