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Chemical Structure| 51068-78-1 Chemical Structure| 51068-78-1

Structure of 51068-78-1

Chemical Structure| 51068-78-1

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Product Details of [ 51068-78-1 ]

CAS No. :51068-78-1
Formula : C6H11NO3
M.W : 145.16
SMILES Code : O=C(N1CCOCC1)CO
MDL No. :MFCD08436413
InChI Key :PHCSTEJVICOGEJ-UHFFFAOYSA-N
Pubchem ID :6480484

Safety of [ 51068-78-1 ]

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

Computational Chemistry of [ 51068-78-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 0
Fraction Csp3 0.83
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 38.1
TPSA ?

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

49.77 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.33
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

-1.87
Log Po/w (WLOGP)?

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

-1.54
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.

-1.26
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

0.05
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.66

Water Solubility

Log S (ESOL):?

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

0.57
Solubility 539.0 mg/ml ; 3.72 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Highly soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

1.34
Solubility 3210.0 mg/ml ; 22.1 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

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

0.18
Solubility 219.0 mg/ml ; 1.51 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

Low
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.

-8.51 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)

1.47

Application In Synthesis of [ 51068-78-1 ]

* 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 [ 51068-78-1 ]

[ 51068-78-1 ] Synthesis Path-Downstream   1~13

  • 1
  • [ 51068-78-1 ]
  • [ 5542-60-9 ]
  • [ 93017-56-2 ]
  • 3
  • [ 1440-61-5 ]
  • [ 51068-78-1 ]
  • [ 74267-28-0 ]
  • 5
  • [ 533925-45-0 ]
  • [ 110-91-8 ]
  • [ 51068-78-1 ]
  • [ 4394-00-7 ]
  • 6
  • [ 110-91-8 ]
  • [ 96-35-5 ]
  • [ 51068-78-1 ]
YieldReaction ConditionsOperation in experiment
at 150℃; for 3h; EXAMPLE 172; 4-[7-(2-Morpholin-4-yl-2-oxo-ethoxy)-quinazolin-4-yl]-piperidine-1-carboxylic acid (4-pyrrolidin-1-yl-phenyl)-amide; a. 4-[7-(2-Morpholin-4-yl-2-oxo-ethoxy)-quinazolin-4-yl]-piperidine-1-carboxylic acid tert-butyl ester; A mixture of morpholine (107.4 mg, 1.23 mmol) and methyl glycolate (77.5 mg, 860 mumol) was stirred at 150° C. for 3 hr. The resulting homogeneous clear amber oil was taken up in toluene (2.x.2 mL) with repeated rotary evaporation to remove methanol. The residue was taken up in dry THF (860 muL) and KOtBu was added (113 mg, 1.01 mmol). The mixture was stirred at 100° C. for 5-10 min until a brown slurry formed with no visible chunks. The mixture was then allowed to cool to rt, 4-(7-fluoro-quinazolin-4-yl)-piperidine-1-carboxylic acid tert-butyl ester (302 mg, 912 mumol), as prepared in Example 65b, was added, and the resulting nearly homogeneous reddish-brown solution was stirred at rt for 1 hr, at which point the reaction solidified into a paste. The reaction was taken up in DCM (4 mL) and washed with 1M NaHCO3 (1.x.2 mL) and 1M NaH2PO4 (1.x.2 mL), and the organic layer was dried (Na2SO4) and concentrated. The residue was purified by silica flash chromatography (9:1 DCM/acetone-->8:2-->8:2 DCM/acetone/3percent DMEA eluent) to provide the title compound as a pale yellow oil (94.8 mg, 24percent over two steps). LC/MS (ESI): calcd mass 456.2, found 457.3 (MH)+.
  • 7
  • [ 51068-78-1 ]
  • [ 79574-71-3 ]
  • [ 1125674-22-7 ]
  • 8
  • [ 51068-78-1 ]
  • [ 916731-80-1 ]
  • [ 916733-39-6 ]
YieldReaction ConditionsOperation in experiment
EXAMPLE 172; 4-[7-(2-Morpholin-4-yl-2-oxo-ethoxy)-quinazolin-4-yl]-piperidine-1-carboxylic acid (4-pyrrolidin-1-yl-phenyl)-amide; a. 4-[7-(2-Morpholin-4-yl-2-oxo-ethoxy)-quinazolin-4-yl]-piperidine-1-carboxylic acid tert-butyl ester; A mixture of morpholine (107.4 mg, 1.23 mmol) and methyl glycolate (77.5 mg, 860 mumol) was stirred at 150° C. for 3 hr. The resulting homogeneous clear amber oil was taken up in toluene (2.x.2 mL) with repeated rotary evaporation to remove methanol. The residue was taken up in dry THF (860 muL) and KOtBu was added (113 mg, 1.01 mmol). The mixture was stirred at 100° C. for 5-10 min until a brown slurry formed with no visible chunks. The mixture was then allowed to cool to rt, 4-(7-fluoro-quinazolin-4-yl)-piperidine-1-carboxylic acid tert-butyl ester (302 mg, 912 mumol), as prepared in Example 65b, was added, and the resulting nearly homogeneous reddish-brown solution was stirred at rt for 1 hr, at which point the reaction solidified into a paste. The reaction was taken up in DCM (4 mL) and washed with 1M NaHCO3 (1.x.2 mL) and 1M NaH2PO4 (1.x.2 mL), and the organic layer was dried (Na2SO4) and concentrated. The residue was purified by silica flash chromatography (9:1 DCM/acetone-->8:2-->8:2 DCM/acetone/3percent DMEA eluent) to provide the title compound as a pale yellow oil (94.8 mg, 24percent over two steps). LC/MS (ESI): calcd mass 456.2, found 457.3 (MH)+.
  • 9
  • [ 6342-79-6 ]
  • [ 622-40-2 ]
  • [ 51068-78-1 ]
  • [ 107-21-1 ]
YieldReaction ConditionsOperation in experiment
With hydrogen;Cu/Al2O3/SiO2; In methanol; at 170℃; under 41254.1 Torr; for 16.5h;Autoclave; HydrogenationThe hydrogenation experiments were performed in a multi-autoclave unit containing four 60 ml batch autoclaves, all equipped with common electrical heating and with individual gas entrainment impellers, manometers and temperature indication . The hydrogenation catalysts were activated in-situ (typical conditions : 230 0C, 10 - 20 bar H2 for 4 hrs ) . The substrates, dissolved in ca . 20 ml solvent , were introduced into the autoclaves by injection. Then, the autoclaves were pressurized with Hz, stirred at 800 rpm and heated to ca. 170 0C. After the reaction, the liquid reactor contents were analyzed by GC-MS. Table 2 shows the reaction conditions and analytical results from the different experiments. Table 23 This specie was qualitatively observed by NMR analysis and/or GC-MS.4 GC-MS peak area percentage (Anpercent) = (peak area n) x 100 / (sum of substrate, 2-hydroxyacetamide, MEG, HOCH2CH2NR2, R2NCH2CH2NR2 and all polyamine peak areas) .5 MEG peak corrected for overlaying methyl glycolate peak (10percent peak area reduction) . n.d. = not determined
  • 11
  • [ 51068-78-1 ]
  • [ 1615254-09-5 ]
  • (S)-tert-butyl (1-(5-(2-morpholino-2-oxoethoxy)-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)ethyl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 288h; Example Id, Preparation of Compound of Formula (Id) A. Preparation of a Compound of Formula (1) in which n is l Rl is 2-{morpholin- 4-yl)-2-oxoethoxy, m is 0, R5 is hydrogen, and R3 is methyl To a solution of (S)-tert~bu.tyl ( 1 -(5-fluoro-4-oxo-3 -phenyl-3 ,4~dihydroquiiiazolra~2~ yt)echyl}carbamate (500 mg, 1 JO mmol) in DMF (2 mL) was added 2-hydroxy-l~ (morpholin-4-yi)ethan-l-one (283 mg, 1.95 mmol) and freshly ground K2CO3 (198 mg, 1.43 mmol). The mixture was heated to 80°C and allowed to stir for 12 days. The reaction was adsorbed directly onto isolute and purified on 1SCG (40 g silica, 0 - 100percent EtOAc/hexane) to give (S)-tert-butyl il-(5-(2~mc>^holmo-2-oxoetiii0xy)^ 2-yl)ethyl)carbamate.
  • 12
  • [ 51068-78-1 ]
  • [ 1446358-48-0 ]
  • C23H20F2N6O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% With lithium hexamethyldisilazane; In tetrahydrofuran; at 23℃; for 5h; Compound 1-11A solution of 2-hydroxy-l-morpholinoethanone (18 mg, 3 equiv.) in THF was treated with LiHMDS (0.120 mL, 3 equiv.) at 23 °C, followed closely with Inter mediate-2 (15 mg, 1 equiv.). The mixture was stirred at 23 °C for 5 h, then partitioned between a 1 : 1 mixture of ethyl acetate and saturated aqueous ammonium chloride solution. The layers were separated, and the aqueous layer was extracted with ethyl acetate (x3). The organic portions were combined and washed with brine. The mixture was dried over MgS04, filtered, and concentrated in vacuo. The crude material was purified via silica gel chromatography utilizing a 0-80percent ethyl acetate/hexanes gradient to deliver the desired compound (14.7 mg, 75percent) as a white solid. 1H-NMR (500 MHz, CDCls) delta 8.47 (d, 1 H), 8.45 (d, 1 H), 7.30 (s, 1 H), 7.23-7.18 (m, 1 H), 7.03 (ddd, 1 H), 6.98 (td, 1 H), 6.85 (td, 1 H), 6.57 (d, 1 H), 5.96 (s, 2 H), 5.21 (s, 2 H), 3.78-3.63 (m, 4 H), 3.63-3.55 (m, 4 H).
  • 13
  • [ 51068-78-1 ]
  • [ 824-94-2 ]
  • C14H19NO4 [ No CAS ]
 

Historical Records

Technical Information

Categories

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[ 51068-78-1 ]

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