Home Cart Sign in  
Chemical Structure| 623564-42-1 Chemical Structure| 623564-42-1

Structure of 623564-42-1

Chemical Structure| 623564-42-1

*Storage: {[sel_prStorage]}

*Shipping: {[sel_prShipping]}

,{[proInfo.pro_purity]}

4.5 *For Research Use Only !

{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]} Purity: {[proInfo.pro_purity]}

Change View

Size Price VIP Price

US Stock

Global Stock

In Stock
{[ item.pr_size ]} Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}

US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days

  • {[ item.pr_size ]}

In Stock

- +

Please Login or Create an Account to: See VIP prices and availability

US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks

  • 1-2 Day Shipping
  • High Quality
  • Technical Support
Product Citations

Alternative Products

Product Details of [ 623564-42-1 ]

CAS No. :623564-42-1
Formula : C7H8N2O2
M.W : 152.15
SMILES Code : O=CC1=CN2C(COCC2)=N1
MDL No. :MFCD11865212
InChI Key :BQGZMWAWDNEWGS-UHFFFAOYSA-N
Pubchem ID :21941356

Safety of [ 623564-42-1 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H317-H319
Precautionary Statements:P280-P305+P351+P338

Computational Chemistry of [ 623564-42-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 5
Fraction Csp3 0.43
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 37.62
TPSA ?

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

44.12 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.98
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

-0.8
Log Po/w (WLOGP)?

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

0.07
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.

-1.15
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

0.91
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.0

Water Solubility

Log S (ESOL):?

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

-0.55
Solubility 42.9 mg/ml ; 0.282 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.

0.35
Solubility 343.0 mg/ml ; 2.25 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

-0.91
Solubility 18.6 mg/ml ; 0.122 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

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.

-7.8 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)

2.29

Application In Synthesis of [ 623564-42-1 ]

* 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.

  • Upstream synthesis route of [ 623564-42-1 ]
  • Downstream synthetic route of [ 623564-42-1 ]

[ 623564-42-1 ] Synthesis Path-Upstream   1~5

  • 1
  • [ 623564-41-0 ]
  • [ 623564-42-1 ]
  • [ 623564-43-2 ]
YieldReaction ConditionsOperation in experiment
36.3%
Stage #1: With toluene-4-sulfonic acid; isopropyl alcohol In cyclohexane at 80℃;
Stage #2: With sodium methylate In methanol; ethanol at 20℃; for 2 h;
Stage #3: With triethylamine In chloroform for 2 h; Heating / reflux
Step 5: 5,6-Dihydro-8H-imidazo[2,1-c][1,4]oxazine-2-carbaldehyde (9) and 56- dihvdro-8H-imidazof2, 1-clf1, 410xazine-3-carbaldehYde; The mixture of 2-bromo-3-hydroxypropenal (4.1 g), p-toluenesulfonic acid monohydrate (52 mg) and 2-propanol (5.2 mL) in cyclohexane (42 mL) was azeotroped until the vapor temperature rose to 80°C. The reaction mixture was concentrated under reduce pressure. The residue was dissolved in dry ethanol (50 mL). A mixture of the dry ethanol (200 mL) solution of 3-iminomorpholin hydrochloride (3.4 g) and 28percent methanol solution of sodium methylat (4.8 g) was added at room temperature. The reaction mixture was stirred at room temperature for 2 h, and then the reaction solvent was removed in vacuo. The residue was dissolved in chloroform (125 mL) and triethylamine (3.5 mL) was added, then the reaction mixture was heated to reflux for 2 h. The reaction mixture was cooled to room temperature and then concentrated under reduce pressure. The residue was dissolved in dichloromethane (300 mL) and washed with 50percent K2CO3 aqueous solution (2 x 100 mL). The organic layer was dried (MgS04) and filtered. The filtrate was concentrated under reduce pressure. The residue was applied to silica gel column chromatography and eluted with CHCI3-acetone (4: 1) to obtain the title (pale orange solid, 1.4 g, 36.3percent) and the other regio isomer. (pale orange solid, 609 mg, 16. 1percent). Desired product :'H NMR (CDCI3) 8 4.08-4. 15 (m, 4H), 4.88 (s, 2H), 7.58 (s, 1H), 9.85 (s, 1H). The unwanted regio isomer :'H NMR (CDCI3) 8 4.06 (t, 2H, J = 5.2 Hz), 4.40 (t, 2H, J = 5. 2 Hz), 4.90 (s, 2H), 7.75 (s, 1H), 9.72 (s, 1H).
References: [1] Patent: WO2003/93279, 2003, A1, . Location in patent: Page/Page column 65-66.
  • 2
  • [ 623564-41-0 ]
  • [ 19263-02-6 ]
  • [ 623564-42-1 ]
  • [ 623564-43-2 ]
YieldReaction ConditionsOperation in experiment
36.3%
Stage #1: With toluene-4-sulfonic acid In cyclohexane; isopropyl alcohol at 80℃;
Stage #2: With sodium methylate In methanol; ethanol at 20℃; for 2 h;
Stage #3: With triethylamine In chloroform for 2 h; Heating / reflux
Step 5: 5. 6-Dihvdro-8H-imidazor2. 1-c1r1. 41oxazine-2-carbaldehyde (9) and 5, 6- dihydro-8H-imidazor2, 1-c1r1, 41Oxazine-3-carbaldehvde The mixture of 2-bromo-3-hydroxypropenal (4.1 g), p-toluenesulfonic acid monohydrate (52 mg) and 2-propanol (5.2 mL) in cyclohexane (42 mL) was azeotroped until the vapor temperature rose to 80°C. The reaction mixture was concentrated under reduce pressure. The residue was dissolved in dry ethanol (50 mL). A mixture of the dry ethanol (200 mL) solution of 3-iminomorpholin hydrochloride (3.4 g) and 28percent methanol solution of sodium methylat (4.8 g) was added at room temperature. The reaction mixture was stirred at room temperature for 2 h, and then the reason solvent was removed in vacuo. The residue was dissolved in chloroform (125 mL) and triethylamine (3.5 mL) was added, then the reaction mixture was heated to reflux for 2 h. The reaction mixture was cooled to room temperature and then concentrated under reduce pressure. The residue was dissolved in dichloromethane (300 mL) and washed with 50percent K2CO3 aqueous solution (2 x 100 mL). The organic layer was dried (MgS04) and filtered. The filtrate was concentrated under reduce pressure. The residue was applied to silica gel column chromatography and eluted with CHCI3-acetone (4: 1) to obtain the title (pale orange solid, 1.4 g, 36.3percent) and the other regio isomer. (pale orange solid, 609 mg, 16. 1percent). Desired product : 1H NMR (CDCI3) 5 4.08-4. 15 (m, 4H), 4.88 (s, 2H), 7.58 (s, 1H), 9.85 (s, 1H). The unwanted regio isomer :'H NMR (CDCI3) 8 4.06 (t, 2H, J = 5.2 Hz), 4.40 (t, 2H, J = 5. 2 Hz), 4.90 (s, 2H), 7.75 (s, 1H), 9.72 (s, 1H).
References: [1] Patent: WO2003/93277, 2003, A1, . Location in patent: Page/Page column 93-94.
  • 3
  • [ 623564-41-0 ]
  • [ 623564-42-1 ]
  • [ 623564-43-2 ]
References: [1] Patent: US2006/276445, 2006, A1, . Location in patent: Page/Page column 17-18.
  • 4
  • [ 623564-41-0 ]
  • [ 155272-73-4 ]
  • [ 623564-42-1 ]
  • [ 623564-43-2 ]
References: [1] Patent: WO2007/16134, 2007, A1, . Location in patent: Page/Page column 37; 38.
  • 5
  • [ 747408-16-8 ]
  • [ 155272-73-4 ]
  • [ 623564-42-1 ]
  • [ 623564-43-2 ]
YieldReaction ConditionsOperation in experiment
25%
Stage #1: at 30 - 35℃; for 2 - 2.5 h;
Stage #2: With potassium carbonate In acetonitrile at 70℃; for 0.25 - 0.5 h;
Example 8Preparation of 5,6-Dihydro-8H-imidazo[2,1-c][1,4]oxazine-2-carbaldehyde (1); Crude morpholin-3-ylideneamine (2) (159.0 g, estimated 60percent to 75percent purity, 1.59 mol) and acetonitrile (1336 mL) were added to a 5-L, four-neck flask equipped with mechanical stirrer, thermocouple, condenser and nitrogen inlet, and the mixture was stirred under nitrogen. 2-bromo-3-isopropoxy-propenal (3) (230 g, 1.19 mol) was dissolved in 690 mL acetonitrile, transferred to a 1-L dropping funnel, and slowly added to the flask over 1 hour to 1.5 hours while the temperature gradually rose to 30° C. to 35° C. The dark mixture was stirred and an HPLC of a sample was taken after 15 to 30 minutes to confirm intermediate formation. After stirring for about 1 hour, solid potassium carbonate (325 mesh) (178.8 g, 1.27 mol, 1.07 equiv.) was added, and the reaction was heated to about 70° C. An HPLC of a sample was taken after 15 to 30 minutes to confirm reaction completion. The stirring mixture was then allowed to cool to 20-30° C. The slurry of solid potassium carbonate (K2CO3) was filtered at room temperature and the solids collected washed with 400 mL acetonitrile. The mother liquors (weighing about 2 kg) were concentrated under reduced pressure (45° C. to 48° C.) to about 335 g of a dark viscous liquid. The concentrate was then partitioned between methylene chloride (DCM) (700 mL) and water (350 mL). The aqueous layer was extracted three times with 200 mL DCM (3.x.200 mL). The combined organic layers were filtered through silica gel (70 g) and the silica gel was washed with 400 mL DCM. The combined filtrates were concentrated until crystallization began. Then t-butyl methyl ether (TBME) was added and the TBME mixture was evaporated, yielding a final weight of about 312 g of slurry of Compound 1. This process was repeated until minimal methylene chloride remained in the orange slurry, as judged by no visible increase in crystallization or no visible decrease in the viscosity of the residual oil, which contained DCM and the regioisomer 16. The amount of methylene chloride may also be determined by NMR, for example. The slurry was filtered, washed with TBME, and dried at room temperature to afford about 60 g of yellow to orange colored product, yielding about 25percent of 5,6-dihydro-8H-imidazo[2,1-c][1,4]oxazine-2-carbaldehyde (Compound 1).Compound 1: Mass spectrometry (M+H): 130.21 amu. 1H NMR (CDCl3) δ 4.08-4.15 (m, 4H), 4.88 (s, 2H), 7.58 (s, 1H), 9.85 (s, 1H). The unwanted regioisomer (16): 1H NMR (CDCl3) δ4.06 (t, 2H, J=5.2 Hz), 4.40 (t, 2H, J=5.2 Hz), 4.90 (s, 2H), 7.75 (s, 1H), 9.72 (s, 1H).
References: [1] Patent: US2009/18332, 2009, A1, . Location in patent: Page/Page column 4; 13-14.
[2] Patent: US2009/18332, 2009, A1, . Location in patent: Page/Page column 14.
[3] Patent: US2009/18332, 2009, A1, . Location in patent: Page/Page column 14.
[4] Patent: US2009/18332, 2009, A1, . Location in patent: Page/Page column 14.
[5] Patent: US2009/18332, 2009, A1, . Location in patent: Page/Page column 14.
[6] Patent: US2009/18332, 2009, A1, . Location in patent: Page/Page column 14.
[7] Patent: US2009/18332, 2009, A1, . Location in patent: Page/Page column 14.
[8] Patent: US2009/18332, 2009, A1, . Location in patent: Page/Page column 14.
[9] Patent: US2009/18332, 2009, A1, . Location in patent: Page/Page column 14.
 

Historical Records

Technical Information

Categories

Related Functional Groups of
[ 623564-42-1 ]

Aldehydes

Chemical Structure| 623564-43-2

A267189 [623564-43-2]

6,8-Dihydro-5H-imidazo[2,1-c][1,4]oxazine-3-carbaldehyde

Similarity: 0.87

Chemical Structure| 68282-52-0

A278253 [68282-52-0]

2,4-Dimethyl-1H-imidazole-5-carbaldehyde

Similarity: 0.67

Chemical Structure| 17289-26-8

A331805 [17289-26-8]

1-Methyl-1H-imidazole-4-carbaldehyde

Similarity: 0.63

Chemical Structure| 202348-55-8

A749163 [202348-55-8]

6-Methylimidazo[1,2-a]pyridine-2-carbaldehyde

Similarity: 0.63

Chemical Structure| 6188-43-8

A131677 [6188-43-8]

Imidazo[1,2-a]pyridine-3-carbaldehyde

Similarity: 0.60

Related Parent Nucleus of
[ 623564-42-1 ]

Other Aromatic Heterocycles

Chemical Structure| 623564-43-2

A267189 [623564-43-2]

6,8-Dihydro-5H-imidazo[2,1-c][1,4]oxazine-3-carbaldehyde

Similarity: 0.87

Chemical Structure| 91476-81-2

A103908 [91476-81-2]

Methyl 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine-2-carboxylate

Similarity: 0.73

Chemical Structure| 1883347-31-6

A228629 [1883347-31-6]

Methyl 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine-2-carboxylate hydrobromide

Similarity: 0.73

Chemical Structure| 77112-53-9

A297640 [77112-53-9]

Imidazo[1,2-a]pyrazine-2-carboxylic acid

Similarity: 0.70

Chemical Structure| 788819-82-9

A128970 [788819-82-9]

Imidazo[1,2-a]pyrazine-6-carboxylic acid

Similarity: 0.69