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Structure of 49608-01-7

Chemical Structure| 49608-01-7

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Product Details of [ 49608-01-7 ]

CAS No. :49608-01-7
Formula : C8H8ClNO2
M.W : 185.61
SMILES Code : CCOC(=O)C1=CN=C(Cl)C=C1
MDL No. :MFCD00082739
InChI Key :ILDJJTQWIZLGPO-UHFFFAOYSA-N
Pubchem ID :2799611

Safety of [ 49608-01-7 ]

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

Computational Chemistry of [ 49608-01-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.25
Num. rotatable bonds 3
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 45.33
TPSA ?

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

39.19 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.18
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

2.28
Log Po/w (WLOGP)?

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

1.91
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.

1.25
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

2.16
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.96

Water Solubility

Log S (ESOL):?

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

-2.6
Solubility 0.467 mg/ml ; 0.00252 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.

-2.74
Solubility 0.338 mg/ml ; 0.00182 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

-3.12
Solubility 0.14 mg/ml ; 0.000753 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

Yes
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.

-5.81 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

1.0 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)

1.72

Application In Synthesis of [ 49608-01-7 ]

* 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 [ 49608-01-7 ]

[ 49608-01-7 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 25999-04-6 ]
  • [ 49608-01-7 ]
  • ethyl 6-[(morpholin-4-ylsulfonyl)amino]nicotinate [ No CAS ]
  • 2
  • [ 49608-01-7 ]
  • [ 21543-49-7 ]
YieldReaction ConditionsOperation in experiment
59% With sodium tetrahydroborate; In methanol; at 0 - 20℃; for 16h; To a solution of 19-2B (500 mg, 2.693 mmol) in MeOH (5 mL) was added sodium borohydride (153 mg, 4.04 mmol) portion wise at 0 C and stirred at RT for 16 hr. The reaction was quenched with saturated ammonium chloride and diluted with EtOAc (50 mL) washed with water (50 mL), brine (20 mL) and dried over Na2S04, and the organic phase was concentrated under reduced pressure to get crude compound. Obtained crude was purified using silica gel chromatography (30% EtOAc in hexanes) to afford 19-3B (230 mg, 1.60 mmol, 59% yield) as a pale yellow solid. MS (ESI): m/z 144.0 (M+l)+.
58% With sodium tetrahydroborate; In ethanol; at 20℃; for 41h; To a solution of ethyl 6-chloronicotinate (25.8 g, 0.139 mol) in ethanol was added sodium borohydride (10.5 g, 0.278 mol), followed by stirring under an atmosphere of nitrogen gas at room temperature. After 41 hours, the reaction mixture was concentrated and then the residue was diluted with a saturated aqueous ammonium chloride solution and ethyl acetate. The organic layer was washed with a saturated aqueous ammonium chloride solution, dried over anhydrous sodium sulfate and concentrated. The residue was subjected to silica gel column chromatography (elution solvent; hexane, hexane:ethyl acetate=4:1, 2:1, and 3:2), to give the title compound (11.7 g, 58%) as a pale yellow solid.1H NMR (400 MHz, DMSO-d6) δ ppm; 4.54 (2H, d, J=5.6Hz), 5.43 (1H, t, J = 5.6 Hz), 7.48 (1H, d, J = 8.4 Hz), 7.80 (1H, dd, J = 2.4, 8.4 Hz), 8.35 (1H, d, J = 2.4 Hz).
With lithium aluminium tetrahydride; In tetrahydrofuran; toluene; at -78 - 0℃; for 1h; EXAMPLE 2; Synthesis of N2- [ (lS)-I- (4-15- [l- (aminocarbonyl) cyclopropyl] pyridin-2-yl} phenyl)-2, 2,2-trifluoroethyl]- Nl- (1-cyanocyclopropyl)-4-fluoro-L-leucinamide; Step 1 : Preparation of (6-chloropyridin-3-yl) methanol; To a-78 C solution of ethyl 6-chloronicotinate (10 g) in 250 mL of THF was slowly added 126 mL of lithium aluminium hydride (1.5 M in toluene). The mixture was stirred at 0 C for 1 hour. Poured into saturated aqueous tartaric acid (200 mL) and extracted with ethyl acetate (2 X 200 mL). The combined extracts were washed with brine, dried with magnesium sulfate and the solvent removed in vacuo. The residue was purified by chromatography on Si02 using ethyl acetate and hexanes (1: 2 to 1: 1) to yield the title compound. 'H NMR (CD3COCD3) 8 8.35 (1H, s), 7.80 (1H, d), 7.40 (1H, d), 4. 68 (2H, d), 4.55 (1H, t).
  • 3
  • [ 845305-83-1 ]
  • [ 49608-01-7 ]
  • [ 845305-95-5 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; at 60℃; Step 1: Ethyl 6-{4-[(1-[(1, 1-DIMETHYLETHYL) oxy] CARBONYL}-4-PIPERIDINYL) OXY]-1- PIPERIDINYL}-3-PYRIDINECARBOXYLATE tert-Butyl 4- (4-piperidinyloxy)-1-piperidinecarboxylate (D4) (1. 7G), potassium carbonate (1.5g) and ethyl 6-chloro-3-pyridinecarboxylate (1.0 G) were heated at 60C under argon overnight. The reaction mixture was evaporated and redissolved in DCM (100 ML) and washed with saturated sodium hydrogen carbonate (3 x 50ml), dried (MgSO4) and evaporated to give a crude product which was chromatographed [silica gel, eluting with (10% NH3 in MeOH/DCM, 0-10%] to give the subtitle compound (1.43 g).
  • 4
  • [ 1196473-37-6 ]
  • [ 49608-01-7 ]
  • [ 1196473-56-9 ]
YieldReaction ConditionsOperation in experiment
To a solution of <strong>[1196473-37-6]3H-benzo[c][1,2]oxaborole-1,6-diol</strong> (1.2 g, 8.0 mmol) in anhydrous dioxane (100 mL) was slowly added KHMDS (48 mL, 0.5 M solution in toluene, 24.0 mmol) at 0° C. After stirring for 15 min at room temperature, 6-chloro-nicotinic acid ethyl ester (2.97 g, 16.0 mmol) was added slowly to the reaction mixture at 0° C. The resulting mixture was stirred at 80° C. for 22 h. The reaction quenched by adding cold brine at 0° C. and the mixture was acidified to pH 3 using diluted hydrochloric acid. The resulting mixture was extract with EtOAc. The extract was washed with brine, dried and concentrated to dryness. The residue was purified by chromatography on silica gel (DCM/methanol=40:1) to give 0.521 g of material. This material was purified by prep-TLC (silica gel, THF/hexanes/AcOH=2:4:trace) to give 0.261 g of purer material which was purified again by chromatography on silica gel (DCM/methanol=40:1) to give 0.109 g of pure product as a pale-yellow solid. Mp 84-85° C. 1H NMR (400 MHz, DMSO-d6) delta 9.23 (s, 1H), 8.68 (d, J=2.34 Hz, 1H), 8.31 (dd, J=8.50, 2.34 Hz, 1H), 7.41-7.54 (m, 2H), 7.30 (dd, J=8.20, 2.34 Hz, 1H), 7.15 (d, J=8.50 Hz, 1H), 5.02 (s, 2H), 4.32 (q, J=7.03 Hz, 2H), 1.31 (t, J=7.03 Hz, 3H). MS (ESI) m/z=300 [M+H]+.
 

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Technical Information

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