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Chemical Structure| 7252-83-7 Chemical Structure| 7252-83-7

Structure of 7252-83-7

Chemical Structure| 7252-83-7

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Product Details of [ 7252-83-7 ]

CAS No. :7252-83-7
Formula : C4H9BrO2
M.W : 169.02
SMILES Code : COC(OC)CBr
MDL No. :MFCD00000213
InChI Key :FUSFWUFSEJXMRQ-UHFFFAOYSA-N
Pubchem ID :81672

Safety of [ 7252-83-7 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H225-H315-H319
Precautionary Statements:P501-P240-P210-P233-P243-P241-P242-P264-P280-P370+P378-P337+P313-P305+P351+P338-P362+P364-P303+P361+P353-P332+P313-P403+P235
Class:3
UN#:1993
Packing Group:

Computational Chemistry of [ 7252-83-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 7
Num. arom. heavy atoms 0
Fraction Csp3 1.0
Num. rotatable bonds 3
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 31.38
TPSA ?

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

18.46 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.99
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

0.85
Log Po/w (WLOGP)?

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

1.0
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.

0.83
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

0.81
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.1

Water Solubility

Log S (ESOL):?

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

-1.23
Solubility 10.1 mg/ml ; 0.0595 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.

-0.82
Solubility 25.5 mg/ml ; 0.151 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

-1.43
Solubility 6.22 mg/ml ; 0.0368 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.

-6.73 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

2.0
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

2.0 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)

2.42

Application In Synthesis of [ 7252-83-7 ]

* 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 [ 7252-83-7 ]

[ 7252-83-7 ] Synthesis Path-Downstream   1~13

  • 1
  • [ 7252-83-7 ]
  • [ 14847-51-9 ]
  • [ 799766-12-4 ]
YieldReaction ConditionsOperation in experiment
36% With sodium ethanolate; In ethanol;Heating / reflux; To a solution of anhydrous ethanol (40 ml), sodium ethoxide (31.7 ml 21% wt. , 86. 94 mmol) and <strong>[14847-51-9]2-bromo-5-methylphenol</strong> (Gewali, Mohan B.; Ronald, Bruce P. J. Org. CHEM. 1980, 45, 2224-2229) (16.25 g, 86.94 mmol) was added 2-BROM-1, 1- dimethoxy ethane (16.17 g, 95.64 mmol). The solution was heated to reflux overnight, reduced under vacuum and partitioned between water and ether. The aqueous layer was extracted with ether and the organics were passed through a silica plug and concentrated to afford 8.71 g (36%) of desired product as a pale yellow oil : H NMR (400 MHz, DMSO-d6): 8 2.19 (3H, s), 3.33 (6H, s), 3.96 (2H, d, J = 5. 1 Hz), 4.64 (1H, t, J = 5.1 Hz), 6.98 (1H, d, J = 8.5 Hz), 7.08 (1H, dd, J = 8.4 Hz, 1.5 Hz), 7.35 (1H, D, J = 1.7 Hz).
  • 2
  • [ 5345-47-1 ]
  • [ 7252-83-7 ]
  • [ 133427-08-4 ]
YieldReaction ConditionsOperation in experiment
In acetonitrile; at 150℃; for 2h;microwave irradiation;Product distribution / selectivity; Example 1.3: Preparation of (4-(2,4-Difluorophenethyl)piperazin-l-yl)(imidazo[l,2- alpha]pyridin-8-yl)methanone (Compound 3).Step A: Preparation of Imidazo[l,2-alpha]pyridine-8-carboxylic Acid.To a mixture of 2-aminonicotinic acid (0.6906 g, 5.00 mmol) in acetonitrile (20 mL) was added bromoacetaldehyde dimethyl acetal (0.591 mL, 5.00 mmol). The resulting slurry was heated at 150 0C under microwave irradiation for 2 h. The resulting precipitate was filtered off and washed with acetonitrile and hexane to afford the title compound (0.924 g) as a grey solid.
0.924 g In acetonitrile; at 150℃; for 2h;Microwave irradiation; To a mixture of 2-aminonicotinic acid (0.69 g, 5.00 mmol) in CH3CN (20 mL) was added bromoacetaldehyde dimethyl acetal (0.59 mL, 5.00 mmol). The resulting slurry was heated to 150 C under microwave irradiation for 2 h. The resulting precipitate was filtered off and washed with CH3CN and hexane to afford H-imidazo[1,2-alpha]pyridine-8-carboxylic acid (0.924 g) as a grey solid.
  • 3
  • [ 6964-21-2 ]
  • [ 7252-83-7 ]
  • [ 691876-20-7 ]
YieldReaction ConditionsOperation in experiment
27% A solution of 3-thienylacetic acid (2.544 g, 17.89 mmol) in dry tetrahydrofuran (100 mL) was cooled with an ICE/SALT bath TO-10 C and the solution of lithium HEXAMETHYLSILAZANE (40 ML, 1M, in THF) was added drop-wise, over a period of 30 minutes. After additional stirring at cold for 30 minutes, the neat 2, 2-DIMETHOXY-1-BROMOETHANE was added via syringe. The cooling bath was removed and the stirring at room temperature was continued for another 3 hrs. The reaction mixture was poured onto water (100 mL), the non-acidic components were extracted with diethyl ether (2 x 50 mL). The pH of the aqueous solution was set to 3, (HCI, 2 N) and the crude acid was extracted into diethyl ether (3 x 50 mL). The combined organic extracts were dried with anhydrous sodium sulfate, and the solvent was evaporated to dryness to leave 1.12 g (27 %) of the crude acid, used in the next step without additional purification. This racemic acid could be resolved into its respective enantiomers using (R)-AND/OR (S) -a- PHENYLETHYLAMINE salts via crystallization from ethyl acetate. The acid, which ultimately led to the more active enantiomer of the racemate shown under Example 30, was obtained by crystallizations using the salts derived form the (S)-AMINE
  • 4
  • [ 7252-83-7 ]
  • [ 51746-85-1 ]
  • [ 439106-42-0 ]
  • [ 1207070-57-2 ]
  • 5
  • [ 7252-83-7 ]
  • [ 1005-38-5 ]
  • [ 872059-27-3 ]
YieldReaction ConditionsOperation in experiment
66% In 1,4-dioxane; water; for 24h;Reflux; Example 9A; 7-Chloro-5-(methylthio)imidazo[1,2-c]pyrimidine 75 g (427 mmol) of 4-amino-6-chloro-2-(methylthio)pyrimidine are dissolved in 3000 ml of dioxane and 750 ml of water. 101.05 g (597.81 mmol) of bromoacetaldehyde dimethyl acetal are added, and the mixture is heated under reflux for 24 h. After the reaction is complete, the dioxane is removed in vacuo and the aqueous suspension is suspended in THF, filtered with suction and washed with some THF. Drying of the solid at 40° C. under high vacuum results in 56.5 g (66percent of theory) of the product.MS (ES+): m/z=200 (M+H)+.1H-NMR (400 MHz, DMSO-d6): delta=8.12 (s, 1H), 7.97 (s, 1H), 7.77 (s, 1H), 2.80 (s, 3H).
  • 6
  • [ 7252-83-7 ]
  • [ 33332-28-4 ]
  • [ 63744-41-2 ]
YieldReaction ConditionsOperation in experiment
25.31% With hydrogen bromide; sodium hydrogencarbonate; In isopropyl alcohol;Reflux; Example 186Preparation of 1-Benzothiazol-6-yl-3-imidazo[1,2-a]pyrazin-5-yl-imidazolidin-2-one (186A) Synthesis of Intermediate 5-Chloro-imidazo[1,2-a]pyrazine (I-186a) NaHCO3 (4.215 g, 50.1736 mmol) and IPA (40 mL) were added to a mixture of 2-bromo-1,1-dimethoxy-ethane (6.37 mL, 10.8066 mmol), 40percent HBr (475 mL, 2.3157 mmol) and 2 drops of water previously refluxed for 1 hr. The reaction mixture was stirred for 5 mins and filtered. To the filtrate was added 6-chloro-pyrazin-2-ylamine (1 g, 7.7190 mmol) and the resulting mixture was refluxed for overnight. The reaction was monitored by TLC (50percent ethylacetate in hexane). The reaction mixture was neutralized with Na2CO3 and partitioned between ethylacetate and water. The organic layer was washed with water, brine, dried over Na2SO4 and concentrated. Purification by column chromatography on silica gel (1-2percent MeOH in CHCl3) afforded 300 mg of the product (25.31percent yield).1H NMR (400 MHz, CDCl3): delta 9.05 (s, 1H), 7.98 (s, 1H), 7.92-7.85 (m, 2H).LCMS: 97.85percent, m/z=154.0 (M+1)
25.31% NaI KX); (4.215g, 50.1736miotanol) and IPA (4OmL) were added to a mixture of 2- 0 brorno- 1.1 -dhneihoxs -ethane (6.37ml... I O.8066mmol), 40percent HBr (475mL. 2.3157mmol ) and 2 drops of water previously reUuxed tor I hr. The reaction mixture was stirred for 5mins and filtered. To the filtrate was added 6-chloro-pyra/in-2-ylamine (I g, 7.7190miotanol) and the resulting mixture was reflux ed for overnight. The reaction was monitored by TLC (50percent ethylacetate in hexane). The reaction mixture was neutrali/od 5 with Na2(X).; and partitioned between ethylacetate and water. The organic layer was washed with water, brine, dried over Na>SO; and concentrated. Purification by column ehromatograph) on silica gel ( 1-2percent McOH in CHC I4) afforded 30(.)mg of the product (25.31percent yield >.1H NMR (400 MIIz, CDCIj): 6 9.05 (s, I M). 7.98 (v IH), 7 92 -7.85 (m. 211).IX MS: 97.85percent. m// 154.0 (M .bul. 1)
  • 7
  • [ 7252-83-7 ]
  • [ 93247-78-0 ]
  • [ 1262419-74-8 ]
YieldReaction ConditionsOperation in experiment
59% Step A: To a stirred solution of methyl lH-indole-7-carboxylate (2.0 g,1 1.4 mmol) in DMF (10 ml) was added sodium hydride (800 mg, 20 mmol) in portions. The mixture was stirred at room temperature for 1 h, then potassium iodide (160 mg, 0.9 mmol) and 2-bromo-l ,l-dimethoxyethane (3.4 ml, 28.5 mmol) were added. The mixture was heated to 80 0C for 15 h. After cooling to room temperature, the reaction was quenched with saturated aqueous ammonium chloride, extracted with ethyl acetate (3chi), washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by column chromatography (silica gel, 70:30 hexanes/ethyl acetate) to afford methyl l-(2,2-dimethoxyethyl)-lH-indole-7-carboxylate (1.77 g, 59percent) as a semitransparent liquid: 1H NMR (500 MHz, CDCl3) delta 7.77 (dd, J = 4.5, 1.0 Hz, I H), 7.66 (dd, J= 4.3, 1.0 Hz, IH), 7.19 (d, J= 1.5 Hz, I H), 7.10 (t, J= 8.0 Hz, I H), 6.57 (d, J = 1.8 Hz, IH), 4.54-4.52 (dd, J= 5.0, 4.5 Hz, IH), 4.48 (d, J= 2.5 Hz, 2H), 3.96 (s, 3H), 3.31 (s, 6H).
  • 8
  • [ 7252-83-7 ]
  • [ 1196473-37-6 ]
  • [ 1268390-26-6 ]
  • 9
  • [ 7252-83-7 ]
  • [ 93247-78-0 ]
  • [ 1262419-75-9 ]
  • 10
  • [ 7252-83-7 ]
  • [ 1458-01-1 ]
  • methyl 5-amino-8-chloroimidazo[1,2-a]pyrazine-6-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
22% In acetonitrile; at 120℃; for 0.666667h;Microwave irradiation; A solution of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (1.2 g, 5.92 mmol, 1.00 equiv) and 2-bromo-1,1-dimethoxyethane (2 g, 11.83 mmol, 2.00 equiv) in acetonitrile (20 mL) was irradiated with microwave for 40 min at 120° C. After completion the resulting solution was concentrated under vacuum and the residue was purified by a silica gel column eluting with dichloromethane/methanol (10:1) to give the title compound (300 mg, 22percent) as a yellow solid. LC-MS (ES, m/z): 227 [M+H]+.
22% In acetonitrile; at 120℃; for 0.666667h;Microwave irradiation; A solution of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (1.2 g, 5.92 mmol, 1.00 equiv) and 2-bromo-1,1-dimethoxyethane (2 g, 11.83 mmol, 2.00 equiv) in acetonitrile (20 mL) wasirradiated with microwave for 40 mm at 120 °C. After completion the resulting solution was concentrated under vacuum and the residue was purified by a silica gel column eluting with dichloromethane/methanol (10:1) to give the title compound (300 mg, 22percent) as a yellow solid. LC-MS (ES, mlz): 227 [M+H].
  • 11
  • [ 7252-83-7 ]
  • [ 4522-35-4 ]
  • 1-(2,2-dimethoxyethyl)-3-iodopyrazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
71.4% With sodium hydride; In mineral oil; at 150℃; for 1h;Microwave irradiation; To a solution of <strong>[4522-35-4]3-iodo-1H-pyrazole</strong> (500 mg, 2.578 mmol) in DMF i10 ml) was addedsodium hydride (1.5 eq., 3 867 mmci, 60% dispersicn n mneral oil, 154.7 mg) and thesuspension allowed to stir or 30 mins until the gas evolution had subsoed. Bromoacetaldehyde dimethyl acetal (1.5 eq. 3.867 mmol, 649.6 mg, 0.4.54 ml) was then added dropwise and the mixtu e heated at 150 C n the microwave for an hour. The mixture was concentrated in vacuo in order to remove as much DMF possible.EtOAc and water were then added to the mixture and the organic layer separated. The aqueous layer was washed twice with. EtOAc and organics combined, dried over MgSO4 and concentrated in vacuo. The product was purified by column chromatography, MeOH/DOM (0-1 %)to give a light orange solid; (519.2 mg, 1.841 mmcl, 71.4 %?,. 1H NMR (500 MHz, CDCI3) 6 7.28 (d, J 2.3, 1 H), 6.40 (d, J 2.3, 1 H),4.62 Ct, J 5.4, 1 H), 4.20 (d, J = 5.4, 2H?j, 3.37 (?d, J = 2.4. 6H 13C NMR (126 MHz, CDCl31 6 132.61 (OH), 9:14.84 (OH), 103.29 (OH2), 94.49 (C). 55.20 (2x OH3, 54 55 (OH); MS (ES ±ve) (M+HY 304.6 (+Na).
  • 12
  • [ 7252-83-7 ]
  • [ 349-58-6 ]
  • 1-(2,2-dimethoxyethoxy)-3,5-bis(trifluoromethyl)benzene [ No CAS ]
  • 13
  • [ 7252-83-7 ]
  • (2S)-2-[(1-but-2-ynoyl)pyrrolidin-2-yl]-4-[4-[(N-pyridin-2-yl)carbamoyl]phenyl]-5-cyanoimidazole [ No CAS ]
  • [ 1420477-60-6 ]
YieldReaction ConditionsOperation in experiment
89.2% To a 250 ml four-necked flask equipped with a stirring, thermometer, and reflux condenser was added 80 g of N, N-dimethylformamide and 8.5 g (0.02 mol) of (S) -2- (1) prepared in Example 7 -But-2-ynylpyrrolidin-2-yl) -4- [4- (pyridin-2-yl) carbamoyl] phenyl-5-cyanoimidazole (VI),3.0 g (0.022 mol) of potassium carbonate, 4.4 g (0.026 mol) of 2-bromoacetaldehyde dimethyl acetal,Stir the reaction at 60 to 65 C for 5 hours, then cool to 20 to 25 C, add 2.7 g (0.05 mol) of ammonium chloride, 8.0 g (0.08 mol) of 17 wt% ammonia water, stir the reaction at 70 to 75 C for 5 hours, and cool to 20 At 25 C, the obtained reaction mixture was added to 200 g of ice water, filtered, and the filter cake was washed twice with water, 20 g each time, and 20 g isopropanol once, and dried to obtain 8.3 g of acortinib. Yield It was 89.2%, and the liquid purity was 99.5%.
 

Historical Records

Technical Information

Categories

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[ 7252-83-7 ]

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