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Structure of 19745-07-4

Chemical Structure| 19745-07-4

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Product Details of [ 19745-07-4 ]

CAS No. :19745-07-4
Formula : C4H2Cl2N2
M.W : 148.98
SMILES Code : C1=NC(=CN=C1Cl)Cl
MDL No. :MFCD04117886
Boiling Point : No data available
InChI Key :JVSDZAGCHKCSGR-UHFFFAOYSA-N
Pubchem ID :336224

Safety of [ 19745-07-4 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 19745-07-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 8
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 32.05
TPSA ?

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

25.78 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.49
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

1.58
Log Po/w (WLOGP)?

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

1.78
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.

0.4
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

2.34
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.52

Water Solubility

Log S (ESOL):?

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

-2.31
Solubility 0.723 mg/ml ; 0.00485 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.

-1.73
Solubility 2.76 mg/ml ; 0.0185 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

-2.87
Solubility 0.203 mg/ml ; 0.00136 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.

-6.09 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

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)

1.96

Application In Synthesis of [ 19745-07-4 ]

* 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 [ 19745-07-4 ]

[ 19745-07-4 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 19745-07-4 ]
  • [ 98-18-0 ]
  • 3-amino-benzenesulfonic acid-(5-chloro-pyrazin-2-ylamide) [ No CAS ]
  • 2
  • [ 19745-07-4 ]
  • [ 103343-37-9 ]
  • [ 123903-93-5 ]
  • 3
  • [ 19745-07-4 ]
  • [ 1435-55-8 ]
  • C44H52N6O4 [ No CAS ]
  • 4
  • [ 19745-07-4 ]
  • C4H7N2O3S(1-)*Na(1+) [ No CAS ]
  • 1-(5-Chloro-pyrazin-2-yl)-3-methanesulfonyl-imidazolidin-2-one [ No CAS ]
  • 5
  • [ 19745-07-4 ]
  • [ 136743-04-9 ]
  • 6
  • [ 89180-45-0 ]
  • [ 19745-07-4 ]
  • 8
  • [ 6863-76-9 ]
  • [ 14508-49-7 ]
  • [ 19745-07-4 ]
  • [ 4858-85-9 ]
  • [ 4774-14-5 ]
  • 10
  • 5-chloro-1<i>H</i>-pyrazin-2-one [ No CAS ]
  • [ 19745-07-4 ]
  • 11
  • [ 290-37-9 ]
  • [ 7732-18-5 ]
  • [ 7782-50-5 ]
  • [ 14508-49-7 ]
  • [ 19745-07-4 ]
  • [ 4858-85-9 ]
  • [ 4774-14-5 ]
  • 12
  • 5-(tributylstannanyl)nicotinic acid ethyl ester [ No CAS ]
  • [ 19745-07-4 ]
  • [ 405939-89-1 ]
  • 13
  • [ 19745-07-4 ]
  • [ 57260-71-6 ]
  • [ 426829-52-9 ]
  • 14
  • [ 19745-07-4 ]
  • [ 57260-71-6 ]
  • [ 479226-58-9 ]
YieldReaction ConditionsOperation in experiment
93% With potassium carbonate; In dimethyl sulfoxide; at 75℃; A solution of <strong>[19745-07-4]2,5-dichloropyrazine</strong> (1.03 g, 6.91 mmol) in DMSO (10 mL) was treated sequentially with K2C03(s) (2.867 g, 20.74 mmol) and tert-butyl piperazine-1-carboxylate (1.288 g, 6.9 14 mmol), then stirred overnight at 75 °C. After cooling to ambient temperature, the mixture was partitioned between EtOAc (10 mL) and water (20 mL). After phase separation, the organic extracts were concentrated in vacuo to provide the title compound (1.928 g, 93percent yield). MS (apci) m/z = 199.1 (M-Boc). ?HNIVIR(CDC13) 8.07 (m, 1H), 7.86 (m, 1H), 3.56 (s, 8H), 1.48 (s, 9H).
With potassium carbonate; In 1-methyl-pyrrolidin-2-one; at 100℃; for 1h; To an NMP (7.5 ml) solution of 1.51 g of <strong>[19745-07-4]2,5-dichloropyrazine</strong> were added 2.00 g of 1-(t-butoxycarbonyl)piperazine and 2.00 g of potassium carbonate, followed by 1 hour of stirring under heating at 100°C. The mixture was cooled to room temperature, and water was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with water and brine and then dried over anhydrous magnesium sulfate, and thereafter, the solvent was evaporated. The residue was purified by silica gel column chromatography (chloroform-methanol) to obtain 2.73 g of 2-chloro-5-(4-t-butoxycarbonylpiperazin-1-yl)pyrazine. Using this compound, 2-chloro-5-{4-[6-(3,4-dimethoxyphenyl)pyridine-2-carbonyl]piperazin-1-yl}pyrazine was obtained in a similar manner to Example 14 as colorless crystals.
  • 15
  • [ 19745-07-4 ]
  • [ 299441-13-7 ]
YieldReaction ConditionsOperation in experiment
With hydrazine; In ethanol; at 20 - 80℃; for 2.75h; [Referential Example 11] 1-(5-Methoxy-2-pyrazinyl)-5-(2-pyridyl)-1H-pyrazole-3-carboxylic acid; [Show Image] [Show Image] 1) 5-Chloro-2-hydrazinopyrazine; A solution of 5-chloro-2-hydroxpyrazine (1.84 g) synthesized from aminopyrazine by the method of Palamidessi et al. (J.Org.Chem., vol.29, pp 2491-2492, 1964) in phosphorus oxychloride (28ml) was placed in a sealed tube, and the solution was stirred at an outer temperature of 130°C for 6 hours. After cooling with air, ice cold water and dichloromethane were added to the reaction liquid, then the phases were separated. The organic layer was dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated under reduced pressure. Hydrazine monohydrate (1.39 ml) was added to a solution of the residue in ethanol (14 ml), and the mixture was stirred at room temperature for 150 minutes and for another 15 minutes at 80°C. After cooling with air, the reaction liquid was evaporated under reduced pressure, and to the residue was added water and a mixed solvent of chloroform and methanol (1:10), then the phases were separated. The organic layer was dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated under reduced pressure to give 5-chloro-2-hydrazinopyrazine(0.325 g, 16percent) as a solid. 1H-NMR (400 MHz, DMSO-d6)delta: 4.32 (2H, br s), 7.92 (1H, s), 7.99 (1H, s), 8.13 (1H, s). EI-MSm/z: 144 (M+).
1.6 g With hydrazine hydrate; In ethanol; at 80℃; for 16h;Inert atmosphere; A mixture of A-63 (10.00 g, 67.12 mmol) in EtOH (80 mL) was stirred under N2 at 80 C for 16 hours. The mixture was concentrated to give the crude product, which was triturated from H20 (20 mL) to give A-64 (1.60 g, 11.07 mmol) as a solid. 1H NMR (400MHz, CDCI3) _ = 8.10 - 8.01 (m, 2H), 6.03 (br s, 1H), 3.85 (br s, 2H).
  • 16
  • [ 33332-29-5 ]
  • [ 19745-07-4 ]
YieldReaction ConditionsOperation in experiment
15% With hydrogenchloride; sodium nitrite; In water; at -10 - 20℃; for 4h; Step 2: Synthesis of 2,5-dichloropyrazine To a stirred solution of 5-chloropyrazin-2-amine (1 g, 7.751 mmol) in conc. HCl (10 mL) was added aq. solution sodium nitrite (1.1 g, 15.89 mmol) at -10° C. over a period of 1 h, stirred for 1 h 0° C. and then at RT for 2 h. Progress of reaction was monitored by TLC. After reaction completion reaction mass neutralised with 50percent NaOH solution and extracted with DCM. The organic layer was dried over sodium sulphate and concentrated under reduced pressure. Crude was purified by silica gel (100-200 mesh) column chromatography using 2percent ethyl acetate in hexane as eluent to yield 2,5-dichloropyrazine (0.59 g, 15percent) as colourless oil. MS: 184.1 [M-1]
With tert.-butylnitrite; copper(l) chloride; copper dichloride; In acetonitrile; at -10 - 65℃; for 3h; Step 2: Preparation of 2,5-dichloropyrazine; 5-Chloropyrazin-2-amine (5.0 g, 38.6 mmol) was dissolved in acetonitrile (77 ml) under a balloon of N2. The copper(I) chloride (5.7 g, 57.9 mmol) and copper(ET) chloride (7.8 g, 57.9 mmol) were added and the slurry cooled to -1O 0C with an ice:acetone bath. t-Butyl nitrite (9.15g, 89 mmol, 90percent) was added dropwise and the solution allowed to warm to RT. The solution was stirred for 30 minutes until rapid gas evolution ceased. The mixture was heated to 65 0C for 2.5 hours. The mixture was cooled to RT and filtered through a 1.5 inch pad of celilte packed into a 465 ml frit. The pad was washed with DCM (200 ml x 4), the wash fractions containing the desired material combined, filtered, and concentrated in vacuo. <n="55"/>The residue was purified by chromatography on silica gel with 2percent etheI.euro.pentane to yield the title compound.
With hydrogenchloride; sodium nitrite; In water; at 0 - 20℃; for 3h; Step 2: 2,5-Dichloropyrazine; 5-Chloro-2-pyrazinamine (product of E1, step 1) (2.41g, 18.6mmole) was dissolved in concentrated hydrochloric acid (24ml), cooled in an ice-acetone bath and treated with a solution of sodium nitrite (2.63g, 38.1 mmole) in water (1 8ml) dropwise over a period of 1 hour. The mixture was cooled in an ice-water bath and left to stir for 1 hour. The mixture was allowed to warm to room temperature over 1 hour, neutralised by addition of sodium hydroxide solution (2M) and extracted with dichloromethane ( x 4). The dichloromethane layers were combined, dried under magnesium sulfate and evaporated in vacuo. The resulting residue was purified by column chromatography (1: 9 ethyl acetate: pentane) to afford the title compound (0.33g). 1H NMR (CDCl3) 8.40 (2H, s).
With hydrogenchloride; sodium nitrite; In water; at 0 - 20℃; for 3h;ice-acetone bath; 5-CHLORO-2-PYRAZINAMINE (D47, Step 1) (2.41 g, 18.6 MMOL) was dissolved in concentrated hydrochloric acid (24 ML), cooled in an ice-acetone bath and treated with a solution of sodium nitrite (2.63 g, 38.1 MMOL) in water (18 ML) dropwise over a period of 1 hour. The mixture was cooled in an ice-water bath and left to stir for 1 hour. The mixture was allowed to warm to room temperature over 1 hour, neutralised by addition of sodium hydroxide solution (2M) and extracted with dichloromethane. The DICHLOROMETHANE layers were combined, dried under magnesium sulfate and evaporated in vacuo. The resulting residue was purified by column chromatography eluting with a mixture of ethyl acetate: pentane (1: 9) to afford the title compound (0.33 g);'H NMR (CDCI3) 8.40 (2H, s).
With hydrogenchloride; sodium nitrite; In water; at 0 - 20℃; for 4h;Ic; Description 5 2,5-Dichloropyrazine (D5); 5-Chloro-2-pyrazinamine (D4) (753 mg, 5.81 mmol) was dissolved in concentrated hydrochloric acid (8 ml), cooled in an ice-acetone bath and treated with a solution of sodium nitrite (822 mg, 11.9 mmol) in water (6 ml) dropwise over a period of 1 hour. The mixture was transferred to an ice-water bath and left to stir for 1 hour. The mixture was allowed to warm to room temperature over 2 hours, neutralised by addition of an aqueous 50percent sodium hydroxide solution and extracted with dichloromethane (x 4). The dichloromethane layers were combined, dried under magnesium sulfate and evaporated. The resulting residue was purified by Biotage column chromatography eluting with 10percent ethyl acetate in pentane to afford the title compound (112 mg). 1H NMR (CDCI3) 8.40 (2H, s).

  • 17
  • [ 19745-07-4 ]
  • [ 1057216-55-3 ]
YieldReaction ConditionsOperation in experiment
Into a 250 ml 3-necked round bottom flask, was placed 45percent hydriodic acid (60 ml). To this was added sodium iodide (25 g, 0.17 mol). To the mixture was added XV-B-86 (10.5 g, 0.07 mol). The resulting solution was allowed to react at room temperature. Adjustment of the pH to >8 was accomplished by the addition of 20 g NaOH in 50 g ice to afford XV-C-86.
  • 18
  • [ 6863-76-9 ]
  • [ 19745-07-4 ]
YieldReaction ConditionsOperation in experiment
37% With trichlorophosphate; at 60 - 70℃; for 1h;Heating / reflux; Into a 250 ml 3-necked round bottom flask, was placed phosphoryl chloride (115 g, 0.75 mol). To the mixture was added XV-A-86(39 g, 0.30 mol), while warming to a temperature of 60-70° C. The resulting solution was heated to reflux, with stirring, for an additional 1 h. After cooling to room temperature, the resulting solution was poured cautiously onto 3000 g of chopped ice with stirring and extracted four times with 800 ml CH2Cl2 and the organic layers combined and concentrated by evaporation under vacuum using a rotary evaporator. The residue was purified by eluting through a column with a 1:10 EtOAc/PE solvent system. The collected fractions were combined and concentrated by evaporation under vacuum using a rotary evaporator. This resulted in 16.5 g (37percent) of compound XV-B-86 as a colorless liquid.
  • 19
  • [ 19745-07-4 ]
  • [ 317828-02-7 ]
  • [ 317828-11-8 ]
YieldReaction ConditionsOperation in experiment
2-[(S)-1-Phenylethylamino]-4-[5-(2-chloropyrazin-5-yl)benzimidazol-1-yl]pyrimidine The title compound was prepared according to the procedure described in EXAMPLE 424, starting from 2-[(S)-1-Phenylethylamino]-4-[5-trimethylstannylbenzimidazol-1-yl]pyrimidine and <strong>[19745-07-4]2,5-dichloropyrazine</strong>. Mass spectrum (ESI) 427.9 (M+).
  • 20
  • [ 89180-45-0 ]
  • [ 19745-07-4 ]
YieldReaction ConditionsOperation in experiment
With trichlorophosphate; at 120℃; for 2h; A mixture of 2-hydroxy-5-chloropyrazine in POCl3 (21 equiv.) was heated at 1200C for 2 h. The reaction mixture was cooled and poured on ice and extracted with dichloromethane. The organic solvent was collected, dried over Na2SO4 and filtered. The solvent was filtered over silica gel followed by ethyl acetate. The solvents were evaporated to provide the title compound
With trichlorophosphate; at 130℃; for 6h; [Referential Example 11] 1-(5-Methoxy-2-pyrazinyl)-5-(2-pyridyl)-1H-pyrazole-3-carboxylic acid; [Show Image] [Show Image] 1) 5-Chloro-2-hydrazinopyrazine; A solution of 5-chloro-2-hydroxpyrazine (1.84 g) synthesized from aminopyrazine by the method of Palamidessi et al. (J.Org.Chem., vol.29, pp 2491-2492, 1964) in phosphorus oxychloride (28ml) was placed in a sealed tube, and the solution was stirred at an outer temperature of 130°C for 6 hours. After cooling with air, ice cold water and dichloromethane were added to the reaction liquid, then the phases were separated. The organic layer was dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated under reduced pressure. Hydrazine monohydrate (1.39 ml) was added to a solution of the residue in ethanol (14 ml), and the mixture was stirred at room temperature for 150 minutes and for another 15 minutes at 80°C. After cooling with air, the reaction liquid was evaporated under reduced pressure, and to the residue was added water and a mixed solvent of chloroform and methanol (1:10), then the phases were separated. The organic layer was dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated under reduced pressure to give 5-chloro-2-hydrazinopyrazine(0.325 g, 16percent) as a solid. 1H-NMR (400 MHz, DMSO-d6)delta: 4.32 (2H, br s), 7.92 (1H, s), 7.99 (1H, s), 8.13 (1H, s). EI-MSm/z: 144 (M+).
  • 21
  • [ 19745-07-4 ]
  • [ 146631-00-7 ]
  • 2-chloro-5-(4-benzyloxyphenyl)pyrazine [ No CAS ]
YieldReaction ConditionsOperation in experiment
2-(4-Benzyloxyphenyl)-5-(6-octyloxypyridin-3-yl)pyrazine STR50 Step 1 In accordance with scheme C-I, 30 g (201 mmol) of <strong>[19745-07-4]2,5-dichloropyrazine</strong> and 45.92 g (201 mmol) of 4-benzyloxyphenylboronic acid are coupled analogously to Example 4a to give 2-chloro-5-(4-benzyloxyphenyl)pyrazine.
  • 22
  • [ 110-85-0 ]
  • [ 19745-07-4 ]
  • [ 84445-51-2 ]
YieldReaction ConditionsOperation in experiment
With concentrated aqueous HCl; In water; acetone; EXAMPLE 1a 1-(5-Chloro-2-pyrazinyl)piperazine A mixture of <strong>[19745-07-4]2,5-dichloropyrazine</strong> (14.9 g, 0.1 mol), piperazine (50.5 g, 0.59 mol), acetone (22.5 ml), water (20 ml) and concentrated aqueous HCl (1.8 ml) was heated at reflux for 3 hr. The reaction mixture was cooled, diluted with water, filtered and the acetone was removed by distillation. The aqueous solution was then extracted thrice with chloroform. The combined extracts were washed twice with water, dried (Na2 SO4) and evaporated to dryness to afford 7.3 g of solid, m.p. 98°-102°. J. K. Boissier et al., J. Med. Chem., 6, 541 (1963) report a m.p. of 101° C.
  • 23
  • [ 19745-07-4 ]
  • [ 61655-60-5 ]
YieldReaction ConditionsOperation in experiment
EXAMPLE 2 5-Chloro-2-(1'-piperazinyl)-pyrazine hydrochloride The title compound, m.p. 301°-302°, is prepared similarly to Example 1 by substituting <strong>[19745-07-4]2,5-dichloropyrazine</strong> for 2,6-dichloropyrazine.
  • 24
  • [ 5382-16-1 ]
  • [ 19745-07-4 ]
  • [ 1020658-72-3 ]
YieldReaction ConditionsOperation in experiment
In isopropyl alcohol; at 160℃; for 0.166667h;Microwave; To a mixture of <strong>[19745-07-4]2,5-dichloropyrazine</strong> in 2-propanol (0.2 M) was added 4- hydroxypiperidine (2.2 equiv.). The reaction was heated in the microwave at 160 0C for 10 min.The solvent was evaporated under reduced pressure and the title compound was purified by flash chromatography eluting with ethyl acetate
  • 25
  • [ 19745-07-4 ]
  • [ 171049-35-7 ]
  • [ 1034824-37-7 ]
YieldReaction ConditionsOperation in experiment
With 1,8-diazabicyclo[5.4.0]undec-7-ene; In 1-methyl-pyrrolidin-2-one; at 110℃; for 1h;Product distribution / selectivity; Step 3: te^butyl-l'-^-chloropyrazin^-yO^^'-bipiperdine-l-carboxylate.; The tert-butyl 4,4'-bipiperidine-l-carboxylate (1.27g, 4.7 mmol) and <strong>[19745-07-4]2,5-dichloropyrazine</strong> (670 mg, 4.5 mmol) were dissolved in NMP (5 ml) at room temperature, and l,8-diazabicyclo[5.4.0]-undec-7-ene (1 mL, 6.8 mmol) added drop-wise. The mixture was heated at 110 0C for Ih, allowed to cool to r.t. and diluted with 50 mL of ethyl acetate. The solution was washed with water (10 mL xl), brine (10 mL xl), dried over magnesium sulfate, filtered, and concentrated in vac. The residue was purified by chromatography on silica gel with 10percent acetone : hexanes to yield the title compound. LC-MS: 381.25 (M+H).
  • 26
  • [ 19745-07-4 ]
  • [ 1078166-48-9 ]
  • [ 1078166-47-8 ]
YieldReaction ConditionsOperation in experiment
80% Preparation 10 1-Benzoyl-3-[(5-chloropyrazin-2-yl)oxy]methyl}azetidine-3-carboxylic acid Sodium hydride (95 mg, 2.38 mmol) was added to anhydrous dimethyl sulphoxide (4 mL) at room temperature and stirred, under a nitrogen atmosphere, for 30 minutes. 1-Benzoyl-3-(hydroxymethyl)azetidine-3-carboxylic acid (255 mg, 1.08 mmol) (Preparation 15) in dimethyl sulphoxide (1 mL) was added drop-wise and the resulting mixture was stirred, at room temperature, for 15 minutes. 2,5-Dichloropyrazine (194 mg, 1.3 mmol) was added and the mixture was stirred, at room temperature, for 3 hours. The reaction mixture was diluted with water (15 mL) and washed with diethyl ether (2*15 mL). The aqueous layer was acidified with aqueous hydrochloric acid (2M, 2 mL) and extracted with dichloromethane (2*15 mL). The combined dichloromethane layers were dried over magnesium sulphate and concentrated. The resulting residue was purified by chromatography on silica gel eluding with ethyl acetate:methanol:acetic acid (95:5:1) to give the title compound, as a colourless gum in 80percent yield, 305 mg. 1H NMR (400 MHz, CDCl3) : 4.32 (m, 2H), 4.54 (d, 1H), 4.75 (m, 3H), 7.4-7.56 (m, 3H), 7.65 (d, 2H), 8.04 (s, 1 H), 8.14 (s, 1H); LRMS APCI m/z 348 [MH]+
  • 27
  • [ 19745-07-4 ]
  • TMPZnCl*LiCl [ No CAS ]
  • C4HCl4LiN2Zn [ No CAS ]
  • [ 51934-41-9 ]
  • [ 1174517-66-8 ]
  • 28
  • [ 19745-07-4 ]
  • TMPZnCl*LiCl [ No CAS ]
  • C4HCl4LiN2Zn [ No CAS ]
  • [ 7553-56-2 ]
  • [ 1174517-52-2 ]
  • 29
  • [ 19745-07-4 ]
  • i-PrMgCl*LiCl [ No CAS ]
  • [ 696-62-8 ]
  • [ 93296-09-4 ]
  • [ 7646-85-7 ]
  • [ 76849-85-9 ]
  • 30
  • [ 19745-07-4 ]
  • [ 720689-55-4 ]
  • 7-[(5-chloro-2-pyrazinyl)oxy]-3-cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepine [ No CAS ]
YieldReaction ConditionsOperation in experiment
3-CYCLOBUTYL-2, 3,4, 5-TETRAHYDRO-1H-BENZO [d] azepin-7-ol (E3) (184 mg, 0.85 MMOL) was dissolved in dry dimethylformamide (3 ml), cooled to 0 °C and treated with sodium hydride (60 percent in mineral oil, 36 mg, 0.89 MMOL). The mixture was allowed to warm to room temperature over 30 minutes. A solution of 2, 5-dichloropyrazine (D47) (139 mg, 0.94 MMOL) in dry dimethylformamide (1 ml) was added and the mixture stirred at room temperature for 5 hours. The mixture was applied to a SCX column and washed with methanol then a mixture of. 880 ammonia/methanol (1: 9). The basic fractions were combined and concentrated in vacuo to afford the title compound (268 mg); MS (ES+) m/e 330 [M+H] +.
  • 31
  • [ 19745-07-4 ]
  • [ 149354-10-9 ]
  • [ 866939-13-1 ]
YieldReaction ConditionsOperation in experiment
Step 3: 1,1-Dimethylethyl 7-[(5-chloro-2-pyrazinyl)oxy]-1,2,4,5-tetrahydro-3H-3- benzazepine-3-carboxylate 1,1-Dimethylethyl 7-hydroxy-1, 2, 4, 5-tetrahydro-3H-3-benzazepine-3-carboxylate (Description 3 of WO 02/40471) (182mg, 0.69mmole) was dissolved in dry dimethylformamide (3ml), cooled to 0°C and treated with sodium hydride (60percent in mineral oil, 29mg, 0.72mmole). The mixture was allowed to warm to room temperature over 60 minutes. A solution of <strong>[19745-07-4]2,5-dichloropyrazine</strong> (product of E1, step 2) (112mg, 0.76mmole) in dry dimethylformamide (1 ml) was added and the mixture stirred at room temperature for 2 hours. The mixture was diluted with water (10ml) and extracted with ethyl acetate (x 2). The ethyl acetate layers were combined, dried under magnesium sulfate and evaporated in vacuo. The residue was purified by column chromatography eluting with ethyl acetate/pentane (1: 4) to afford the title compound (208mg). MS (ES+) m/e 376 [M+H]+.
Description 6 1,1-Dimethylethyl 7-[(5-ch loro-2-pyrazi nyl)oxy]-1,2,4,5-tetrahyd ro-3H-3-benzazepi ne- 3-carboxylate (D6); 1,1-Dimethylethyl 7-hydroxy-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate (182 mg, 0.69 mmol: obtainable by the process described in Description 3 from WO 02/40471) was dissolved in dry dimethylformamide (3 ml), cooled in an ice bath and treated with sodium hydride (60 percent in mineral oil, 29 mg, 0.72 mmol). The mixture was allowed to warm to room temperature over 1 hour. A solution of <strong>[19745-07-4]2,5-dichloropyrazine</strong> (D5) (112 mg, 0.76 mmol) in dimethylformamide was added and the mixture stirred at room temperature for 2 hours and left to stand overnight under argon. The mixture was diluted with water and extracted with ethyl acetate (x 2). The ethyl acetate layers were combined, dried under magnesium sulfate and evaporated. The residue was purified by Biotage column chromatography, eluting with 1: 4 ethyl acetate: pentane to afford the title compound (208 mg). MS (ES+) m/e 376 [M+H]+.
  • 32
  • [ 19745-07-4 ]
  • [ 401-81-0 ]
  • [ 1233493-46-3 ]
  • 33
  • [ 19745-07-4 ]
  • [ 1521-51-3 ]
  • [ 1233493-45-2 ]
  • 34
  • [ 19745-07-4 ]
  • [ 6601-37-2 ]
  • [ 1245215-80-8 ]
YieldReaction ConditionsOperation in experiment
25.5% Preparation of N-fdelta-chloroDyrazin^-vD-N-methylethanesulfonamide (SM-9):(SM-9)To a solution of N-methyl-ethanesufonamide (400 mg, 3.25 mmol) in methanol (2.2 ml_) was added potassium hydroxide (85percent, 214 mg, 3.25 mmol). Solvent was removed and the potassium salt was suspended in dimethylsulfoxide (1.0 ml_) and added to a stirred solution of 2,5- dichloropyrazine (484 mg, 3.25 mmol) in dimethylsufoxide (1.0 ml_). The resulting dark colored reaction mixture was stirred at room temp for 45 minutes. The reaction mixture was quenched in ice water and the dark suspension was extracted three times with dichloromethane. The combined organics were washed with brine, dried over sodium sulfate and flash chromatographed eluting with a 0-40percent gradient of ethyl acetate in heptane to afford N-(5-chloropyrazin-2-yl)-N-methyl ethanesulfonamide (SM-9: 195 mg, 25.5percent).1H NMR (400 MHz, CHLOROFORM-d) ppm 1.32 (t, J=7.43 Hz, 3 H), 3.26 (q, J=7.30 Hz, 2 H), 3.42 (s, 3 H), 8.32 (d, J=1.37 Hz, 1 H), 8.56 (d, J=1.17 Hz, 1 H). MS (M+1 ) 236.0.
  • 35
  • [ 19745-07-4 ]
  • [ 51067-38-0 ]
  • [ 76849-86-0 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; at 85℃; for 2h;Inert atmosphere; To a solution of <strong>[19745-07-4]2,5-dichloropyrazine</strong> (2.91 mmole) in 1,2-dimethoxyethane (9 mL), was added 4-(phenoxyphenyl)lboronic acid (3.49 mmole) and tetrakis(triphenylphosphine)palladium (0.145 mmole) followed by 2M Na2CO3 (3 mL). The resulting mixture was heated at 85 C for 2 hours. The reaction mixture was diluted with ethyl acetate and filtered through celite. The organic extract was dried over Na2SO4 and evaporated in vacuo. The crude product was purifed by biotage chromatography and then with prep TLC eluting with 5percent ethyl acetate and hexane mixture to give 2-chloro-5-(4-phenoxyphenyl)pyrazine.
 

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