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Structure of 1268810-09-8

Chemical Structure| 1268810-09-8

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Product Details of [ 1268810-09-8 ]

CAS No. :1268810-09-8
Formula : C10H15NO2
M.W : 181.23
SMILES Code : O=C(OC(C)(C)C)NC1(C#C)CC1
MDL No. :MFCD22548363
InChI Key :QVGLHHJMUIIWAA-UHFFFAOYSA-N
Pubchem ID :72218569

Safety of [ 1268810-09-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338

Computational Chemistry of [ 1268810-09-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 0
Fraction Csp3 0.7
Num. rotatable bonds 4
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 50.78
TPSA ?

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

38.33 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.51
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

1.39
Log Po/w (WLOGP)?

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

1.69
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.

1.61
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

1.56
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.75

Water Solubility

Log S (ESOL):?

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

-1.58
Solubility 4.82 mg/ml ; 0.0266 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.

-1.8
Solubility 2.88 mg/ml ; 0.0159 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

-1.73
Solubility 3.36 mg/ml ; 0.0185 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.

-6.42 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)

2.56

Application In Synthesis of [ 1268810-09-8 ]

* 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 [ 1268810-09-8 ]

[ 1268810-09-8 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 558-13-4 ]
  • tert-butyl (1-(2,2-dibromovinyl)cyclopropyl)carbamate [ No CAS ]
  • [ 107259-06-3 ]
  • [ 1268810-09-8 ]
YieldReaction ConditionsOperation in experiment
Three 250mL flask was added triphenylphosphine (45. 4g, 0 · 17mol, 4eq) and DCM (255g), the reaction solution was cooled down to0~5 C, was added CBr4 (28. 6g, 0. 086mol, 2eq), the red color of the solution no mention, 20min after the solid precipitation.Four batches Compound 2Α (8g, 0. 043πο1, leq), heat obvious, 0 C reaction 0. 5h. The solid was removed by filtration, and concentrated,Brush silica gel, the eluent was concentrated to give a pale yellow solid 13. 7g.[0047] 4 NMR (400MHz, CDC13):... Δ = 6. 687 (s, 1H), 1 453 (s, 9H), 1 288 (m, 2H), 1 253 (m,2H) ppm; ESI / MS: m / z = 342 (Μ + Η) +.[0048] The light yellow solid (270mL) was added in THF, cooled to -78 C, dropping 2. 5Mn-BuLi / hexane solutionLiquid (53mL, 0 130mol, 3eq.), - 78 C reaction 30min, was slowly warmed to -40 C, the reaction 30min. Slowly at -40 CDropwise addition of water (lmL), was slowly warmed to room temperature and extracted with ethyl acetate (100mL * 2), dried and concentrated to give a solid. N-heptylDioxane (20g) was added to the solid, stirred 30min, filtered and dried to afford Compound 3A as a white solid (6. 6g, yield:84%, purity: 94.1%)
  • 2
  • C10H15Cl2NO2 [ No CAS ]
  • [ 107259-06-3 ]
  • [ 76-03-9 ]
  • [ 1268810-09-8 ]
YieldReaction ConditionsOperation in experiment
77% three flask was added compound 24 (28,0.0111111,169) and 01 ^ (201 ^), added dropwise at room temperatureTCA (2 · 6g, 0 · 016mol, 1 · 5eq), at room temperature was added in three portions sodium trichloroacetate (3g, 0 · 015mol, 1 · 6eq),Room temperature 4h. Cooled to 0 C, was added dropwise acetic anhydride (2. 2g, 0. 022mol, 2eq), was slowly warmed to room temperature, room temperaturelh. Acetic acid (25mL), cooled to 0 C, was added zinc dust (1.48,0.02 111,269), warmed to 55~60 (:, transShould lh. Slow cooling to room temperature, water (200 mL), filtered, MTBE extract (50mL * 2), the combined organic phases with saturated common saltWashed with water (30mL * l), the organic phase was concentrated, brush silica, eluant was concentrated to give a pale yellow solid 2. 4g.2. 4g solid was added to the three 100mL flask was added THF (30mL), cooled to -30 C, was added dropwise 1. 6M AButyl lithium / diethyl ether solution (18mL, 0. 03mol, 3eq), low temperature reaction lh, slowly warmed to room temperature. Aqueous solution of ammonium chloride(100 mL), extracted with ethyl acetate (50mL * 2), and the combined organic phase was concentrated to give a solid, n-heptane (10g) was added to the solid,Stirred for 30min, filtered and dried to afford Compound 3A as a white solid (1. 5g, Yield: 77%, purity: 952%)
  • 3
  • [ 56-23-5 ]
  • C10H15Cl2NO2 [ No CAS ]
  • [ 107259-06-3 ]
  • [ 1268810-09-8 ]
YieldReaction ConditionsOperation in experiment
74% 250mL three neck flask was added triphenylphosphine (11. 3g, 0. 044mol, 4eq) and DCM (255g), the reaction solutionCooled to 0~5 C, was added CC14 (11. 4g, 0 · 022mol, 2eq), stirred for 30min. Compound was added in four batches2Α (2g, 0. 01 lmo 1,1 eq), heat obvious, 0 C reaction 0. 5h. Filtered to remove solids, and concentrated, brush silica gel, eluent concentrationCondensing pale yellow solid 2. 5g. ESI / MS: m / z = 253 (M + H) +.[0078] (50mL) of the pale yellow solid was added THF, cooled to -78 C, was added dropwise 2. 5Μ n-BuLi / hexane solution(13mL, 0 · 033mol, 3eq), - 78. . The reaction 30min, slowly warmed to -40. . The reaction 30min. -40. . Slowly droppedWater (50 mL), was slowly warmed to room temperature and extracted with ethyl acetate (50mL * 2), dried and concentrated to give a solid. N-Heptane (10g)Was added to the solid, stirred for 30min, filtered and dried to afford Compound 3A as a white solid (1. 45g, yield: 74%, pureDegree: 95 · 1%)
  • 4
  • [ 507-25-5 ]
  • C10H15I2NO2 [ No CAS ]
  • [ 107259-06-3 ]
  • [ 1268810-09-8 ]
YieldReaction ConditionsOperation in experiment
250mL three neck flask was added triphenylphosphine (11. 3g, 0 · 044mol, 4eq) and DCM (255g), the reactionWas cooled to 0~5 C, was added CI4 (11. 4g, 0. 022mol, 2eq), stirred for 30min. Four batches Compound 2Α (2g, 0. 01 lmo 1,1 eq), heat obvious, 0 C reaction 0. 5h. Filtered to remove solids, and concentrated, brush silica gel, eluent concentrationReduced to give a yellow solid 4. 3g. ESI / MS: m / z = 436 (M + H) +.[0073] (50mL) of the pale yellow solid was added THF, cooled to -78 C, was added dropwise 2. 5Μ n-BuLi / hexane solution(13mL, 0 · 033mol, 3eq), - 78. . The reaction 30min, slowly warmed to -40. . The reaction 30min. -40. . Slowly droppedWater (50 mL), was slowly warmed to room temperature and extracted with ethyl acetate (50mL * 2), dried and concentrated to give a solid. N-Heptane (10g)Was added to the solid, stirred for 30min, filtered and dried to afford Compound 3A as a white solid (1. 55g, yield: 79%, pureDegree: 94 · 6%)
  • 6
  • [ 90965-06-3 ]
  • [ 107259-06-3 ]
  • [ 1268810-09-8 ]
YieldReaction ConditionsOperation in experiment
Dimethyl (1-diazo-2-oxopropyl)phosphonate (443 mL) was dissolved in MeCN (0222) (25 mL) and potassium carbonate (767 mg) was added. The suspension was stirred at room temperature for 10 minutes, then the freshly prepared aldehyde 14 (428 mg) in MeOH (9 mL) was added. Stirring was continued overnight. The solvents were removed in vacuo and the residue was dissolved in 1 :1 mixture of Et20/water. The layers were separated and the organic layer was washed with water and brine, and dried (Na2S04). The yellowish oil was purified by FCC (1 :2 EtOAc/heptane) to give product 15 as a pale white solid. 1H NMR (300 MHz, CDCIs) d = 5.00 (s, 1 H), 2.13 (s, 1 H), 1.46 (s, 9H), 1.23 - 1.16 (m, 2H), 1.12 - 1.01 (m, 2H). 13C NMR (75 MHz, CDCIs) d = 155.47, 85.80, 80.34, 66.75, 28.49, 23.72, 18.13.
 

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