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Chemical Structure| 7343-33-1 Chemical Structure| 7343-33-1

Structure of 7343-33-1

Chemical Structure| 7343-33-1

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Product Details of [ 7343-33-1 ]

CAS No. :7343-33-1
Formula : C2H2BrN3
M.W : 147.96
SMILES Code : BrC1=NC=NN1
MDL No. :MFCD09055371
InChI Key :HHIZISRHAQPAMY-UHFFFAOYSA-N
Pubchem ID :139000

Safety of [ 7343-33-1 ]

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

Computational Chemistry of [ 7343-33-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 6
Num. arom. heavy atoms 5
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 24.08
TPSA ?

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

41.57 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.48
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

1.01
Log Po/w (WLOGP)?

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

0.57
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.

-0.49
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

1.89
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.69

Water Solubility

Log S (ESOL):?

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

-2.01
Solubility 1.44 mg/ml ; 0.00977 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.

-1.47
Solubility 4.99 mg/ml ; 0.0337 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

-1.69
Solubility 2.99 mg/ml ; 0.0202 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.

-6.49 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)

2.12

Application In Synthesis of [ 7343-33-1 ]

* 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 [ 7343-33-1 ]

[ 7343-33-1 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 7343-33-1 ]
  • [ 5977-14-0 ]
  • [ 64-17-5 ]
  • [ 41081-90-7 ]
  • 2
  • [ 7343-33-1 ]
  • [ 5977-14-0 ]
  • [ 35523-67-2 ]
  • 3
  • [ 7343-33-1 ]
  • [ 108-24-7 ]
  • [ 129053-59-4 ]
  • 6
  • [ 7343-33-1 ]
  • [ 159209-57-1 ]
  • [ 76279-98-6 ]
  • [ 105958-58-5 ]
  • 1-(2-methoxycarbonylethyl)-3-nitro-1,2,4-triazolone [ No CAS ]
  • 3-(3-Bromo-5'-nitro-[1,3']bi[[1,2,4]triazolyl]-2'-yl)-propionic acid methyl ester [ No CAS ]
  • 7
  • [ 7343-33-1 ]
  • [ 121900-00-3 ]
  • [ 623577-63-9 ]
YieldReaction ConditionsOperation in experiment
45% With copper diacetate; N,N,N',N'-tetramethylguanidine; In tetrahydrofuran; at 50℃; for 16h; A mixture of 3-brom-1, 2, 4-lH-triazole (prepared as described in Chemische Berichte 1967, 100, 2250) (1.0 g, 6.76 mmol), tri (4- fluorophenyl) bismuth acetate (prepared by the method described in Synthetic Communications 1996,4569) (4.53 g, 7.4 mmol), copper (II) acetate (0.25 g, 20molpercent) and N, N, N', N'-tetramethylguanidine (1.7 mL, 13.5 mmol) in dry tetrahydrofuran (30 mL) was stirred at 50OC under a balloon of air for 16 hr. The suspension was poured into water (100 mL) and 1M citric acid (30 mL) to give a suspension of pH 3-4. Ethyl acetate (100 mL) was added and the mixture was filtered through Celite , washing the filter cake with ethyl acetate (100 mL). The two phases of the filtrate were separated and the organic layer was dried (Na2SO4) and concentrated. Flash column chromatography on silica gel, eluting with 25percent then 40percent ethyl acetate-isohexane, gave 1- (4-fluorophenyl)-3-bromo- 1,2, 4-lH-triazole as an off-white solid (0.74 g, 45percent). 8 (iH, 400MHz, CDCl3) 7.18-7. 24 (2H, m), 7.60-7. 65 (2H, m), 8.37 (1H, s). MS (ES+) 242,244 ([MH] +).
  • 8
  • [ 61-82-5 ]
  • [ 7343-33-1 ]
  • 9
  • [ 7343-33-1 ]
  • [ 121900-00-3 ]
  • [ 623577-63-9 ]
  • 10
  • [ 7343-33-1 ]
  • [ 768-94-5 ]
  • [ 1207947-26-9 ]
  • 11
  • [ 7343-33-1 ]
  • [ 350-46-9 ]
  • [ 1129540-71-1 ]
  • 12
  • [ 7343-33-1 ]
  • [ 194222-05-4 ]
  • [ 1233323-97-1 ]
YieldReaction ConditionsOperation in experiment
With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 20℃; for 18h; Example 52Preparation of Compound 71 Step A - Synthesis of Compound 52BCompound 52A (1.08 g, 4.8 mmol) was combined with 3-brorno-[1 ,2,4]triazole (0.70 g, 4.7 mmol), trtphenylphosphine (1.49 g, 5.7 mmol) and diisopropyl azodicarboxylate (1.12 mL, 5.7 mmol) in THF (15 mL). The resulting reaction was allowed to stir at room temperature for 18 hours, then the reaction mixture was concentrated in vacuo to provide Compound 52B, which was used without further purification.
  • 13
  • [ 7343-33-1 ]
  • [ 1207755-28-9 ]
  • [ 76-05-1 ]
  • (1S,4aR,6aS,7R,8R,10aR,10bR,12aR,14R,15R)-15-[[(2R)-2-amino-2,3-dimethylbutyl]oxy]-14-(5-bromo-1H-1,2,4-triazol-1-yl)-8-[(1R)-1,2-dimethylpropyl]-1,6,6a,7,8,9,10,10a,10b,11,12,12a-dodecahydro-1,6a,8,10a-tetramethyl-4H-1,4a-propano-2H-phenanthro[1,2-c]pyran-7-carboxylic acid trifluoroacetate [ No CAS ]
  • (1S,4aR,6aS,7R,8R,10aR,10bR,12aR,14R,15R)-15-[[(2R)-2-amino-2,3-dimethylbutyl]oxy]-14-(3-bromo-4H-1,2,4-triazol-4-yl)-8-[(1R)-1,2-dimethylpropyl]-1,6,6a,7,8,9,10,10a,10b,11,12,12a-dodecahydro-1,6a,8,10a-tetramethyl-4H-1,4a-propano-2H-phenanthro[1,2-c]pyran-7-carboxylic acid trifluoroacetate [ No CAS ]
  • (1S,4aR,6aS,7R,8R,10aR,10bR,12aR,14R,15R)-15-[[(2R)-2-amino-2,3-dimethylbutyl]oxy]-14-(3-bromo-1H-1,2,4-triazol-1-yl)-8-[(1R)-1,2-dimethylpropyl]-1,6,6a,7,8,9,10,10a,10b,11,12,12a-dodecahydro-1,6a,8,10a-tetramethyl-4H-1,4a-propano-2H-phenanthro[1,2-c]pyran-7-carboxylic acid trifluoroacetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
EXAMPLE 6 fPROCEDURES)(1 S,4a/?,6aS,7/?,8/?, 1 Oa/?, 10b/?, 12a/?, 1 AR, 15R)- 15-[[(2/?)-2-amino-2,3- dimethylbutyl]oxy]-14-(3-bromo-4H-l,2,4-triazol-4-yl)-8-[(l/?)-l,2-dimethylpropyl]-1 ,6,6a,7,8,9, 10, 10a, 10b, 11 , 12, 12a-dodecahydro- 1 ,6a,8, 10a-tetramethyl-4//- 1 ,4a-propano-2H- phenanthro[l,2-c]pyran-7-carboxylic acid (EXAMPLE 6A) and(1 S,4a/?,6aS,7/?,8/?, 1 Oa/?, 10b/?, 12a/?, 14/?, 15R)- 15-[[(2/?)-2-amino-2,3- dimethylbutyl]oxy]-14-(5-bromo-/H-l,2,4-triazol-l-yl)-8-[(l/?)-l,2-dimethylpropyl]-1 ,6,6a,7,8,9, 10, 10a, 10b, 11 , 12, 12a-dodecahydro- 1 ,6a,8, 1 Oa-tetramethyl-4//- 1 ,4a-propano-2H- phenanthro[l,2-c]pyran-7-carboxylic acid (EXAMPLE 6B) and( 1 S,4aR,6aS,7R,8R, 1 Oa/?, 1 Obi?, 12aK, 1 AR, 15R)- 15-[[(2i?)-2-amino-2,3- dimethylbutyl]oxy]-14-(3-bromo-7H-l,2,4-triazol-l-yl)-8-[(li?)-l,2-dimethylpropyl]- 1 ,6,6a,7,8,9, 10, 1 Oa, 1 Ob, 11 , 12, 12a-dodecahydro- 1 ,6a,8, 1 Oa-tetramethyl-^H- 1 ,4a-propano-2H- phenanthro[l,2-c]pyran-7-carboxylic acid (EXAMPLE 6C)3-bromo-lH-l,2,4-triazole (32.1 mg, 0.217 mmol) and BF3OEt2 (54 mul, 0.426 mmol) were added to a stirred solution of Intermediate 6 (26.0 mg, 0.043 mmol) in 1,2- dichloroethane (0.43 ml). The reaction mixture was a light yellow solution that was heated to 5O0C. After 1.75 hr, LCMS and 1H NMR showed complete consumption of Intermediate 6. The reaction mixture was cooled to room temperature, the solvent was evaporated, and the resulting residue was placed under high vacuum. The residue was dissolved in methanol and separated using a single HPLC run on a 19 x 150 mm Sunfire Prep Cl 8 OBD 10 mum column by eluting with acetonitrile/water + 0.1percent TFA. The HPLC fractions containing the fastest eluting regioisomer were combined, the solvent was evaporated under reduced pressure, and the residue was lyophilized from ethanol and benzene to give EXAMPLE 6A (3.6 mg) as a white solid. The HPLC fractions containing the second eluting regioisomer were combined, the solvent was evaporated under reduced pressure, and the residue was lyophilized from ethanol and benzene to give EXAMPLE 6B (13.1 mg) as a white solid. The HPLC fractions containing the slowest eluting regioisomer were combined, the solvent was evaporated under reduced pressure, and the residue was lyophilized from ethanol and benzene to give EXAMPLE 6C (5.8 mg) as a white solid.EXAMPLE 6A: 1H NMR (CD3OD, 600 MHz, ppm) delta 0.76 (s, 3H, Me), 0.76 (d, 3H, Me), 0.81 (d,3H, Me), 0.84 (d, 3H, Me), 0.85 (d, 3H, Me), 0.88 (s, 3H, Me), 0.89 (d, 3H, Me), 0.94 (s, 3H, Me), 1.16 (s, 3H, Me), 1.20 (s, 3H, Me), 1.22-1.35 (m), 1.40-1.44 (m), 1.46-1.65 (m), 1.73-1.96 (m), 2.11-2.22 (m), 2.43 (broad dd, IH, H13), 2.79 (broad d, IH), 2.84 (s, IH, H7), 3.49 (d, IH), 3.53 (d, 2H), 3.60 (d, IH), 3.73 (broad d, IH), 3.94 (d, IH), 5.50 (dd, IH, H5), 5.72-5.80 (broad m, IH, H 14), 9.29 (broad s, IH, triazole).Mass Spectrum: (ESI) m/z = 717.32 (719.32) (M+H).EXAMPLE 6B:1H NMR (CD3OD, 600 MHz, ppm) delta 0.75 (s, 3H, Me), 0.76 (d, 3H, Me), 0.79 (d, 3H, Me), 0.83 (d, 3H, Me), 0.84 (d, 3H, Me), 0.88 (s, 3H, Me), 0.89 (d, 3H, Me), 0.91 (s, 3H, Me), 1.13 (s, 3H, Me), 1.19 (s, 3H, Me), 1.22-1.34 (m), 1.39-1.43 (m), 1.46-1.56 (m), 1.58-1.64 (m), 1.72-1.95 (m), 2.09-2.21 (m), 2.30 (dd, IH, H13), 2.83 (s, IH, H7), 2.85 (d, IH), 3.48 (d, IH), 3.48 (d, IH), 3.54 (dd, IH), 3.60 (d, IH), 3.88 (d, IH), 3.95 (d, IH), 5.47 (dd, IH, H5), 5.71-5.77 (m, IH, H14), 8.10 (s, IH, triazole). Mass Spectrum: (ESI) m/z = 717.32 (719.32) (M+H).EXAMPLE 6C:1H NMR (CD3OD, 600 MHz, ppm) delta 0.76 (s, 3H, Me), 0.77 (d, 3H, Me), 0.82 (d, 3H, Me), 0.85 (d, 3H, Me), 0.86 (s, 3H, Me), 0.86 (d, 3H, Me), 0.89 (d, 3H, Me), 0.92 (s, 3H, Me), 1.16 (s, 3H, Me), 1.20 (s, 3H, Me), 1.22-1.34 (m), 1.39-1.44 (m), 1.48-1.65 (m), 1.76-1.96 (m), 2.11-2.22 (m), 2.41 (dd, IH, H13), 2.72 (d, IH), 2.84 (s, IH, H7), 3.47 (d, IH), 3.50 (d, IH), 3.52 (dd, IH), 3.58 (d, IH), 3.72 (d, IH), 3.91 (d, IH), 5.48 (dd, IH, H5), 5.51-5.57 (m, IH, H 14), 8.52 (s, IH, triazole).Mass Spectrum: (ESI) m/z = 717.32 (719.32) (M+H).
<strong>[7343-33-1]3-bromo-1H-1,2,4-triazole</strong> (32.1 mg, 0.217 mmol) and BF3OEt2 (54 mul, 0.426 mmol) were added to a stirred solution of Intermediate 6 (26.0 mg, 0.043 mmol) in 1,2- dichloroethane (0.43 ml). The reaction mixture was a light yellow solution that was heated to 50°C. After 1.75 hr, LCMS and 1H NMR showed complete consumption of Intermediate 6. The reaction mixture was cooled to room temperature, the solvent was evaporated, and the resulting residue was placed under high vacuum. The residue was dissolved in methanol and separated using a single HPLC run on a 19 x 150 mm Sunfire Prep C18 OBD 10 mum column by eluting with acetonitrile/water + 0.1percent TFA. The HPLC fractions containing the fastest eluting regioisomer were combined, the solvent was evaporated under reduced pressure, and the residue was lyophilized from ethanol and benzene to give EXAMPLE 6A (3.6 mg) as a white solid. The HPLC fractions containing the second eluting regioisomer were combined, the solvent was evaporated under reduced pressure, and the residue was lyophilized from ethanol and benzene to give EXAMPLE 6B (13.1 mg) as a white solid. The HPLC fractions containing the slowest eluting regioisomer were combined, the solvent was evaporated under reduced pressure, and the residue was lyophilized from ethanol and benzene to give EXAMPLE 6C (5.8 mg) as a white solid.EXAMPLE 6A:1H NMR (CD3OD, 600 MHz, ppm) delta 0.76 (s, 3H, Me), 0.76 (d, 3H, Me), 0.81 (d, 3H, Me), 0.84 (d, 3H, Me), 0.85 (d, 3H, Me), 0.88 (s, 3H, Me), 0.89 (d, 3H, Me), 0.94 (s, 3H, Me), 1.16 (s, 3H, Me), 1.20 (s, 3H, Me), 1.22-1.35 (m), 1.40-1.44 (m), 1.46-1.65 (m), 1.73-1.96 (m), 2.11-2.22 (m), 2.43 (broad dd, 1H, H13), 2.79 (broad d, 1H), 2.84 (s, 1H, H7), 3.49 (d, 1H), 3.53 (d, 2H), 3.60 (d, 1H), 3.73 (broad d, 1H), 3.94 (d, 1H), 5.50 (dd, 1H, H5), 5.72-5.80 (broad m, 1H, H14), 9.29 (broad s, 1H, triazole). Mass Spectrum: (ESI) m/z = 717.32 (719.32) (M+H).EXAMPLE 6B:1H NMR (CD3OD, 600 MHz, ppm) delta 0.75 (s, 3H, Me), 0.76 (d, 3H, Me), 0.79 (d, 3H, Me), 0.83 (d, 3H, Me), 0.84 (d, 3H, Me), 0.88 (s, 3H, Me), 0.89 (d, 3H, Me), 0.91 (s, 3H, Me), 1.13 (s, 3H, Me), 1.19 (s, 3H, Me), 1.22-1.34 (m), 1.39-1.43 (m), 1.46-1.56 (m), 1.58-1.64 (m), 1.72-1.95 (m), 2.09-2.21 (m), 2.30 (dd, 1H, H13), 2.83 (s, 1H, H7), 2.85 (d, 1H), 3.48 (d, 1H), 3.48 (d, 1H), 3.54 (dd, 1H), 3.60 (d, 1H), 3.88 (d, 1H), 3.95 (d, 1H), 5.47 (dd, 1H, H5), 5.71-5.77 (m, 1H, H14), 8.10 (s, 1H, triazole).Mass Spectrum: (ESI) m/z = 717.32 (719.32) (M+H).EXAMPLE 6C:1H NMR (CD3OD, 600 MHz, ppm) delta 0.76 (s, 3H, Me), 0.77 (d, 3H, Me), 0.82 (d, 3H, Me), 0.85 (d, 3H, Me), 0.86 (s, 3H, Me), 0.86 (d, 3H, Me), 0.89 (d, 3H, Me), 0.92 (s, 3H, Me), 1.16 (s, 3H, Me), 1.20 (s, 3H, Me), 1.22-1.34 (m), 1.39-1.44 (m), 1.48-1.65 (m), 1.76-1.96 (m), 2.11-2.22 (m), 2.41 (dd, 1H, H13), 2.72 (d, 1H), 2.84 (s, 1H, H7), 3.47 (d, 1H), 3.50 (d, 1H), 3.52 (dd, 1H), 3.58 (d, 1H), 3.72 (d, 1H), 3.91 (d, 1H), 5.48 (dd, 1H, H5), 5.51-5.57 (m, 1H, H 14), 8.52 (s, 1H, triazole).Mass Spectrum: (ESI) m/z = 717.32 (719.32) (M+H).
  • 14
  • [ 7343-33-1 ]
  • [ 1207755-56-3 ]
  • [ 76-05-1 ]
  • (1S,4aR,6aS,7R,8R,10aR,10bR,12aR,14R,15R)-14-(5-bromo-1H-1,2,4-triazol-1-yl)-8-[(1R)-1,2-dimethylpropyl]-15-[(tetrahydro-4-(methylamino)-2H-pyran-4-yl)methoxy]-1,6,6a,7,8,9,10,10a,10b,11,12,12a-dodecahydro-1,6a,8,10a-tetramethyl-4H-1,4a-propano-2H-phenanthro[1,2-c]pyran-7-carboxylic acid trifluoroacetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
A solution of Intermediate 28 (250 mg, 0.397 mmol) in dichloroethane (4 mL) was treated with 3-bromo-iH-1,2,4-triazole (294 mg, 1.98 mmol) then BF3OEt;? (0.503 mL, 3.97 mmol) and this mixture was heated to 55°C under nitrogen. After 1 hour the reaction was cooled to room temperature then concentrated in vacuo. The crude product mixture was suspended in methanol (3 mL) and filtered through a sintered glass funnel. The filtrate was purified by preparative EtaPLC (19 x 100 mm Waters Sunfire column, 5 mum, UV-detection, 30-100percentMeCN/water with 0.05percent TFA over 20 minutes). The fractions containing the clesired product (major regioisomer) were combined and partially concentrated by rotovap then frozen and lyophilized to give the title compound (80 mg) was a white amorphous solid.1H NMR (CD3OD, 500 MHz, ppm) delta 0.78 (s, 3H), 0.79 (d, 3H, partially obscured), 0.87 (d, J=6.6 Hz, 3H), 0.91 (d, 3H, partially obscured), 0.92 (s, 3H), 1.15 (s, 3H), 1.22 (s, 3H), 1.23 -1.98 (m), 2.14 (m, 1H), 2.20 (m, 1H), 2.31 (dd, J=13.5, 6.4 Hz, 1H), 2.45 (s, 3H), 2.85 (s, 1H),2.91 (m, 1H), 3.32-3.35 ( m, 1H, partially obscured), 3.37 ( d, J=I 1.2 Hz, 1H), 3.53 (d, 1H, partially obscured), 3.56 (dd, 1H, partially obscured), 3.60 (m, 1H, partially obscured), 3.67 (m, 1H,), 3.80 (m, 1H, partially obscured), 3.82(d, 1H, partially obscured), 3.90(d, J=12.2 Hz, 1H), 4.09 (d, J=9.8 Hz, 1H), 5.49 (m, 1H), 5.76 (m, 1H), 8.14 (s, 1H). Mass spectrum: (ESI) m/z = 147 AS (M+H).
  • 15
  • [ 7343-33-1 ]
  • [ 76513-69-4 ]
  • [ 1260599-41-4 ]
YieldReaction ConditionsOperation in experiment
Sodium hydride (1.2eq) was added to a solution of 3-bromo-lH-[l,2,4]triazole (leq) in dry DMF (2.3ml/mmol) at 00C and under an atmosphere of nitrogen The solution was stirred at 00C for 20min, then, SEM-Cl (1.2eq) was added. The mixture was stirred at room temperature overnight and diluted with H2O and ethyl acetate. The organic layers was washed with H2O then brine, dried on anhydrous Na2SO4, filtered and concentrated in vacuum to give the titled compound. Crude compound 3- bromo-l-(2-trimethylsilanyl-ethoxymethyl)-lH-[l,2,4]triazole was engaged in step 2 without purification. IH-NMR (CDCl3): delta (ppm) 0.00 (t, 9H); 0.92 (t, 2H); 3.64 (t, 2H); 5.44 (s, 2H); 8.13 (s, IH)
  • 16
  • [ 7343-33-1 ]
  • [ 1313006-28-8 ]
  • [ 1313280-86-2 ]
YieldReaction ConditionsOperation in experiment
15% at 150℃; (f?)-2-(6-Fluoroimidazo[1 ,2-a]pyridin-3-yl)-N-(piperidin-3-yl)pyrimidin-4-amine (42 mg, 0.13 mmol, Preparation 9b) and 3-bromo-1 H-1 ,2,4-triazole (10 mg, 0.07 mmol, prepared as described in the J. Med. Chem. 2004, 47(19), 4645-4648) are heated overnight at 150 °C. The crude reaction mixture is directly purified by reverse phase chromatography (C-18 silica from Waters, water/1 :1 acetonitrile-methanol as eluents [0.1percent v/v formic acid buffered] 0percent to 100percent) to obtain the title compound (4 mg, 15percent) as a solid.LRMS (m/z): 380 (M+1)+.1H-NMR delta (CDCIa): 1.8 (m, 2H), 1.9 (m, 1 H), 2.0 (m, 1 H), 3.2 (m, 1 H), 3.3 (m,1 H), 3.7 (m, 1 H), 4.1 (m, 2H), 5.2 (bs, 1 H), 6.1 (m, 1 H), 7.2 (m, 1 H), 7.6 (dd,1 H), 7.8 (m, 1 H), 8.1 (m, 1 H), 8.5 (s, 1 H), 9.8 (m, 1 H).
  • 17
  • [ 7343-33-1 ]
  • [ 1331768-88-7 ]
  • [ 1331768-69-4 ]
YieldReaction ConditionsOperation in experiment
52% at 150℃; A mixture of (f?)-A/-(piperidin-3-yl)-2-(pyrazolo[1 ,5-a]pyridin-3-yl)pyrimidin-4-amine (Preparation 34, 298 mg, 1.01 mmol) and <strong>[7343-33-1]3-bromo-1H-1,2,4-triazole</strong> (75 mg, 0.51 mmol, prepared as described in Journal of Medicinal Chemistry, 2004, 47 (19), 4645- 4648) was heated at 150 °C overnight. The crude mixture was purified by reverse phase chromatography (C-18 silica from Waters.(C)., water/acetonitrile/methanol as eluents [0.1percent v/v formic acid buffered] 0percent to 100percent) to give the title compound (96 mg, 52percent) as a white solid.LRMS (m/z): 362 (M+1)+.1H NMR delta (300 MHz, DMSO-d6): 1.5 (d, 1 H), 1.7 (ms, 1 H), 1.8 (m, 1 H), 2.0 (m, 1 H), 2.8 (m, 1H), 3.0 (m, 1 H), 3.4 (m, 1 H), 3.7 (m, 1 H), 4.2 (m, 2H), 6.3 (bs, 1 H), 7.0 (t, 1 H), 7.3 (m, 1 H), 7.4 (m, 1H), 8.1 (m, 1 H), 8.2 (s, 1 H), 8.5 (m, 1 H), 8.6 (s, 1 H), 8.8 (d, 1 H).
  • 18
  • [ 7343-33-1 ]
  • [ 103962-05-6 ]
  • [ 1417885-96-1 ]
YieldReaction ConditionsOperation in experiment
73% With copper(l) iodide; caesium carbonate; In dimethyl sulfoxide; at 100℃; for 36h;Inert atmosphere; A dry round bottom flask was charged with <strong>[7343-33-1]3-bromo-1H-1,2,4-triazole</strong> (5 g, 33.8 mmol), CuI (0.644 g, 3.38 mmol), and Cs2CO3 (11.01 g, 33.8 mmol). The flask was evacuated/backfilled with N2, then DMSO (33.8 mL) and 1-iodo-4-(trifluoromethoxy)benzene (4.87 g, 16.90 mmol) were added. The reaction mixture was heated to 100° C. for 36 h. The reaction mixture was cooled to room temperature, diluted with EtOAc, filtered through a plug of Celite® and further washed with EtOAc. Water was added to the combined organics, and the layers were separated. The aqueous phase was neutralized to pH 7, and further extracted with EtOAc. The combined organics were concentrated in vacuo. Purification via flash chromatography (silica/EtOAc/Hexanes) yielded 3-bromo-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole as an off white solid (3.78 g, 73percent yield): mp 67-69° C.; 1H NMR (400 MHz, CDCl3) delta 8.43 (s, 1H), 7.70 (m, 2H), 7.38 (m, 2H); 19F NMR (376 MHz, CDCl3) delta -58.02.
73% With copper(l) iodide; caesium carbonate; In dimethyl sulfoxide; at 100℃; for 20h;Inert atmosphere; To a 250 mL reaction flask was added <strong>[7343-33-1]3-bromo-1H-1,2,4-triazole</strong> (5 g, 33.8 mmol), CuI (0.644 g, 3.38 mmol) and Cs2CO3 (11.01 g, 33.8 mmol). The flask was evacuated/backfilled with nitrogen gas, and then DMSO (33.8 ml) and 1-iodo-4-(trifluoromethoxy)benzene (4.87 g, 16.90 mmol) were added. The reaction mixture was heated to 100° C. for 20 hours (h). The reaction was cooled to room temperature, diluted with EtOAc and filtered through a plug of Celite®. The Celite® was further washed with EtOAc. Water was added to the combined organics, and the layers were separated. The aqueous phase was neutralized to pH 7, and further extracted with EtOAc. The combined organics were concentrated in vacuo. Purification via flash column chromatography using EtOAc/hexanes as eluent to yield the title compound (3.78 g, 73percent): mp 69-70° C.; 1H NMR (400 MHz, CDCl3) delta 8.44 (s, 1H), 7.70 (d, J=8.9 Hz, 2H), 7.38 (d, J=8.5 Hz, 2H); 19F NMR (376 MHz, CDCl3) delta ?58.04; EIMS m/z 307 ([M]+).
73% With copper(l) iodide; caesium carbonate; In dimethyl sulfoxide; at 100℃; for 20h;Inert atmosphere; To a 250 mL reaction flask was added <strong>[7343-33-1]3-bromo-1H-1,2,4-triazole</strong> (5 g, 33.8 mmol), CuI (0.644 g, 3.38 mmol) and Cs2CO3 (11.01 g, 33.8 mmol). The flask was evacuated/backfilled with nitrogen gas, and then DMSO (33.8 ml) and 1-iodo-4-(trifluoromethoxy)benzene (4.87 g, 16.90 mmol) were added. The reaction mixture was heated to 100° C. for 20 hours (h). The reaction wascooled to room temperature (RT), diluted with EtOAc and filtered through a plug of Celite®. The Celite® was further washed with EtOAc. Water was added to the combined organics, and the layers were separated. The aqueous phase was neutralized to pH 7, and further extracted with EtOAc. The combined organics were concentrated in vacuo. Purification via flash column chromatography using EtOAc/hexanes as eluent provided the title compound as an off-white solid (3.78 g, 73percent): mp 69-70° C.; 1H NMR (400 MHz, CDCl3) delta 8.44 (s, 1H), 7.70 (d, J=8.9 Hz, 2H), 7.38 (d, J=8.5 Hz, 2H); 19F NMR (376 MHz, CDCl3) delta-58.04; EIMS m/z 307 ([M]+)
72.6% With copper(l) iodide; caesium carbonate; In dimethyl sulfoxide; at 100℃; for 20h;Inert atmosphere; Example 59. Preparation of 3-bromo-l-(4-(trifluoromethoxy)phenyl)-lH-l,2,4-triazole (B61) To a 250 mL reaction flask was added 3-bromo-lH-l,2,4-triazole (5 g, 33.8 mmol), copper(I) iodide (0.644 g, 3.38 mmol) and cesium carbonate (11.01 g, 33.8 mmol). The flask was evacuated/backfilled with N2, then DMSO (33.8 ml) and l-iodo-4-(trifluoromethoxy)benzene (4.87 g, 16.90 mmol) were added. The reaction mixture was heated to 100 °C for 20 h. The reaction was cooled to room temperature, diluted with EtOAc and filtered through a plug of Celite. The Celite was further washed with EtOAc. Water was added to the combined organics, and the layers were separated. The aqueous phase was neutralized to pH 7, and further extracted with EtOAc. The combined organics were concentrated in vacuo. Purification via flash chromatography (silica/EtO Ac/Hex) yielded 3-bromo-l-(4- (trifluoromethoxy)phenyl)-lH-l,2,4-triazole as an off white solid (3.78 g, 12.27 mmol, 72.6percent): mp 69-70 °C; ]H NMR (400 MHz, CDC13) delta 8.44 (s, 1H), 7.70 (d, / = 8.9 Hz, 2H), 7.38 (d, J = 8.5 Hz, 2H); 19F NMR (376 MHz, CDC13) delta -58.04; EIMS m/z 307.
72.6% With copper(l) iodide; caesium carbonate; In dimethyl sulfoxide; at 100℃; for 20h;Inert atmosphere; To a 250 mL reaction flask was added <strong>[7343-33-1]3-bromo-1H-1,2,4-triazole</strong> (5 g, 33.8 mmol), CuI (0.644 g, 3.38 mmol) and Cs2CO3 (11.01 g, 33.8 mmol). The flask was evacuated/backfilled with nitrogen gas, and then DMSO (33.8 ml) and 1-iodo-4-(trifluoromethoxy)benzene (4.87 g, 16.90 mmol) were added. The reaction mixture was heated to 100° C. for 20 hours (h). The reaction was cooled to room temperature (RT), diluted with EtOAc and filtered through a plug of Celite®. The Celite® was further washed with EtOAc. Water was added to the combined organics, and the layers were separated. The aqueous phase was neutralized to pH 7, and further extracted with EtOAc. The combined organics were concentrated in vacuo. Purification via flash chromatography (silica/EtOAc/hexanes) yielded 3-bromo-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole as an off-white solid (3.78 g, 12.27 mmol, 72.6percent): mp 69-70° C.; 1H NMR (400 MHz, CDCl3) delta 8.44 (s, 1H), 7.70 (d, J=8.9 Hz, 2H), 7.38 (d, J=8.5 Hz, 2H); 19F NMR (376 MHz, CDCl3) delta ?58.04; EIMS m/z 307.
72.6% With copper(l) iodide; caesium carbonate; In dimethyl sulfoxide; at 100℃; for 36h;Inert atmosphere; Example 6 Preparation of 3-bromo-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole A dry round bottom flask was charged with <strong>[7343-33-1]3-bromo-1H-1,2,4-triazole</strong> (5 g, 33.8 mmol), CuI (0.644 g, 3.38 mmol), and Cs2CO3 (11.01 g, 33.8 mmol). The flask was evacuated/backfilled with N2, then DMSO (33.8 mL) and 1-iodo-4-(trifluoromethoxy)benzene (4.87 g, 16.90 mmol) were added. The reaction mixture was heated to 100° C. for 36 h. The reaction mixture was cooled to room temperature, diluted with EtOAc, filtered through a plug of Celite® and further washed with EtOAc. Water was added to the combined organics, and the layers were separated. The aqueous phase was neutralized to pH 7, and further extracted with EtOAc. The combined organics were concentrated in vacuo. Purification via flash column chromatography (EtOAc/hexanes) yielded the title compound as an off white solid (3.78 g, 72.6percent): mp 67-69° C.; 1H NMR (400 MHz, CDCl3) delta 8.43 (s, 1H), 7.70 (m, 2H), 7.38 (m, 2H); 19F NMR (376 MHz, CDCl3) delta -58.02. Example 5 Preparation of 3-bromo-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole A dry round bottom flask was charged with potassium phosphate (K3PO4, 7.74 g, 36.5 mmol), CuI (0.165 g, 0.868 mmol), and <strong>[7343-33-1]3-bromo-1H-1,2,4-triazole</strong> (2.83 g, 19.10 mmol). The flask was evacuated/backfilled with N2 (3*). DMF (34.7 mL) was added, followed by trans-(1R,2R)-N,N'-bismethyl-1,2-cyclohexane diamine (0.274 ml, 1.736 mmol) and 1-iodo-4-(trifluoromethoxy)benzene (5.000 g, 17.36 mmol). The solution was heated to 110° C. After 48 h, the reaction mixture was cooled to room temperature, diluted with EtOAc and filtered through Celite®. The filtrate was washed with water (100 mL) containing HCl (1 M, 10 mL. The organics were separated, and the aqueous phase was further extracted with EtOAc (3*). The organics were combined, dried, and concentrated in vacuo. Purification via flash column chromatography (EtOAc/hexanes) yielded the title compound as a tan solid (1.86 g, 34percent): 1H NMR (400 MHz, CDCl3) delta 8.44 (s, 1H), 7.70 (d, J=8.9 Hz, 2H), 7.38 (d, J=8.5 Hz, 2H); 19F NMR (376 MHz, CDCl3) delta -58.04; EIMS m/z 307.
54% With copper(l) iodide; caesium carbonate; In dimethyl sulfoxide; at 100℃; for 20h;Inert atmosphere; To a 100 mL round bottomed flask, equipped with a stir bar, was added copper(I) iodide (0.397 g, 2.08 mmol), <strong>[7343-33-1]3-bromo-1H-1,2,4-triazole</strong> (4.62 g, 31.2 mmol), and cesium carbonate (6.79 g, 20.83 mmol), as solids. These solids were diluted with anhydrous dimethyl sulfoxide (34.7 mL). Then 1-iodo-4-(trifluoromethoxy)benzene (1.65 mL, 10.4 mmol) was added as a liquid. The flask was placed under nitrogen atmosphere, and the suspension was heated to an internal temperature of 100° C. for 20 hours. The reaction mixture was allowed to cool to room temperature and filtered through a pad of Celite®, washing with excess ethyl acetate (200 mL). The filtrate was poured into a brine solution (200 mL), and the layers were partitioned. The aqueous phase was extracted with additional ethyl acetate (2*100 mL). The combined organic layers were dried over anhydrous magnesium sulfate, filtered, and concentrated. The resulting residue was purified via flash column chromatography using 10-50percent ethyl acetate/hexanes as eluent to afford the title compound as a white solid (1.80 g, 54percent): 1H NMR (400 MHz, DMSO-d6) delta 9.35 (s, 1H), 7.97 (d, J=8.9 Hz, 2H), 7.60 (d, J=8.4 Hz, 2H); 19F NMR (376 MHz, DMSO-d6) delta -57.06; ESIMS m/z 308, 310 ([M+H]+).
34% With copper(l) iodide; (R,R)-N,N'-dimethyl-1,2-diaminocyclohexane; In N,N-dimethyl-formamide; at 110℃; for 48h;Inert atmosphere; A dry round bottom flask was charged with potassium phosphate (K3PO4, 7.74 g, 36.5 mmol), CuI (0.165 g, 0.868 mmol), and <strong>[7343-33-1]3-bromo-1H-1,2,4-triazole</strong> (2.83 g, 19.10 mmol). The flask was evacuated/backfilled with N2 (3*). DMF (34.7 ml) was added, followed by trans-(1R,2R)-N,N'-bismethyl-1,2-cyclohexane diamine (0.274 ml, 1.736 mmol) and 1-iodo-4-(trifluoromethoxy)benzene (5 g, 17.36 mmol). The solution was heated to 110° C. After 48 h, the reaction mixture was cooled to RT, diluted with EtOAc and filtered through Celite®. The filtrate was washed with water (100 mL) containing 10 mL 1 M HCl. The organics were separated, and the aqueous phase was further extracted with EtOAc (3*). The organics were combined, dried, and concentrated in vacuo. Purification via flash column chromatography (EtOAc/hexanes) yielded the title compound as a tan solid (1.86 g, 34percent): 1H NMR (400 MHz, CDCl3) delta 8.44 (s, 1H), 7.70 (d, J=8.9 Hz, 2H), 7.38 (d, J=8.5 Hz, 2H); 19F NMR (376 MHz, CDCl3) delta -58.04; EIMS m/z 307 ([M]+).
With copper(l) iodide; caesium carbonate; In dimethyl sulfoxide; at 100℃; for 20h;Inert atmosphere; To a 250 mL reaction flask was added 3-bromo-lH-l,2,4-triazole (5 g, 33.8 mmol), copper(I) iodide (0.644 g, 3.38 mmol) and cesium carbonate (11.01 g, 33.8 mmol). The flask was evacuated/backfilled with N2, then DMSO (33.8 ml) and l-iodo-4-(trifluoromethoxy)benzene (4.87 g, 16.90 mmol) were added. The reaction mixture was heated to 100 °C for 20 h. The reaction was cooled to room temperature, diluted with EtOAc and filtered through a plug of Celite. The Celite was further washed with EtOAc. Water was added to the combined organics, and the layers were separated. The aqueous phase was neutralized to pH 7, and further extracted with EtOAc. The combined organics were concentrated in vacuo.Purification via flash chromatography (silica/EtO Ac/Hex) yielded 3-bromo-l-(4- (trifluoromethoxy)phenyl)-lH-l,2,4-triazole as an off white solid (3.78 g, 12.27 mmol,72.6percent): mp 69-70 °C; ]H NMR (400 MHz, CDC13) delta 8.44 (s, 1H), 7.70 (d, / = 8.9 Hz, 2H), 7.38 (d, J = 8.5 Hz, 2H); 19F NMR (376 MHz, CDC13) delta -58.04; EIMS m/z 307.
With caesium carbonate; In water; dimethyl sulfoxide; Example 6 Preparation of 3-bromo-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole A dry round bottom flask was charged with <strong>[7343-33-1]3-bromo-1H-1,2,4-triazole</strong> (5 g, 33.8 mmol), CuI (0.644 g, 3.38 mmol), and Cs2CO3 (11.01 g, 33.8 mmol). The flask was evacuated/backfilled with N2, then DMSO (33.8 mL) and 1-iodo-4-(trifluoromethoxy)benzene (4.87 g, 16.90 mmol) were added. The reaction mixture was heated to 100° C. for 36 h. The reaction mixture was cooled to RT, diluted with EtOAc, filtered through a plug of Celite® and further washed with EtOAc. Water was added to the combined organics, and the layers were separated. The aqueous phase was neutralized to pH 7, and further extracted with EtOAc. The combined organics were concentrated in vacuo. Purification via flash column chromatography EtOAc/hexanes yielded the title compound as an off white solid (3.78 g, 73percent): mp 67-69° C.; 1H NMR (400 MHz, CDCl3) delta 8.43 (s, 1H), 7.70 (m, 2H), 7.38 (m, 2H); 19F NMR (376 MHz, CDCl3) delta-58.02.
With caesium carbonate; In water; dimethyl sulfoxide; Example 6 Preparation of 3-bromo-1-(4-(trifluoromethoxy)Phenyl)-1H-1,2,4-triazole A dry round bottom flask was charged with <strong>[7343-33-1]3-bromo-1H-1,2,4-triazole</strong> (5 g, 33.8 mmol), CuI (0.644 g, 3.38 mmol), and Cs2CO3 (11.01 g, 33.8 mmol). The flask was evacuated/backfilled with N2, then DMSO (33.8 mL) and 1-iodo-4-(trifluoromethoxy)benzene (4.87 g, 16.90 mmol) were added. The reaction mixture was heated to 100° C. for 36 h. The reaction mixture was cooled to RT, diluted with EtOAc, filtered through a plug of Celite® and further washed with EtOAc. Water was added to the combined organics, and the layers were separated. The aqueous phase was neutralized to pH 7, and further extracted with EtOAc. The combined organics were concentrated in vacuo. Purification via flash column chromatography (EtOAc/Hexanes) yielded the title compound as an off white solid (3.78 g, 73percent): mp 67-69° C.; 1H NMR (400 MHz, CDCl3) delta 8.43 (s, 1H), 7.70 (m, 2H), 7.38 (m, 2H); 19F NMR (376 MHz, CDCl3) delta -58.02.
3 g With copper(l) iodide; caesium carbonate; In dimethyl sulfoxide; at 130℃; for 18h;Inert atmosphere; Sealed tube; To a mixture of 1 -iodo-4-(trifluoromethoxy)benzene (3 g, 10.416 mmol) in methylsulfinylmethane (24 mL) was added 3-bromo-1 H-1 ,2,4-triazole (3.1 g) under nitrogen atmosphere followed by addition of cesium carbonate (6.7 g, 20.833 mmol) and copper iodide (0.4 g, 2.083 mmol). The reaction mass was stirred at 130°C for 18 hours in seal tube. The reaction mass was then diluted with water and extracted with ethylacetate (3 x 70 mL). The combined organic layers were then dried over sodium sulphate and concentrated under reduced pressure followed by column chromatography to obtain the title compound as solid (3 g). (0581) H NMR (400 MHz, (CD3)3SO): delta 9.38 - 9.25 (m, 1 H), 7.98 - 7.92 (m, 2H), 7.65 - 7.53 (m, 2H) LC/MS (method E) m/z: 308 [M + H]+, Rt = 0.94 min.

  • 19
  • [ 7343-33-1 ]
  • potassium phosphate [ No CAS ]
  • [ 68737-65-5 ]
  • [ 103962-05-6 ]
  • [ 1417885-96-1 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; In N,N-dimethyl-formamide; Example 5 Preparation of 3-bromo-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole A dry round bottom flask was charged with potassium phosphate (K3PO4, 7.74 g, 36.5 mmol), CuI (0.165 g, 0.868 mmol), and <strong>[7343-33-1]3-bromo-1H-1,2,4-triazole</strong> (2.83 g, 19.10 mmol). The flask was evacuated/backfilled with N2 (3*). DMF (34.7 ml) was added, followed by trans-(1R,2R)-N,N'-bismethyl-1,2-cyclohexane diamine (0.274 ml, 1.736 mmol) and 1-iodo-4-(trifluoromethoxy)benzene (5 g, 17.36 mmol). The solution was heated to 110° C. After 48 h, the reaction mixture was cooled to RT, diluted with EtOAc and filtered through Celite®. The filtrate was washed with water (100 mL) containing HCl (1 M, 10 mL). The organics were separated, and the aqueous phase was further extracted with EtOAc (3*). The organics were combined, dried, and concentrated in vacuo. Purification via flash column chromatography EtOAc/hexanes yielded the title compound as a tan solid (1.86 g, 34percent): 1H NMR (400 MHz, CDCl3) delta 8.44 (s, 1H), 7.70 (d, J=8.9 Hz, 2H), 7.38 (d, J=8.5 Hz, 2H); 19F NMR (376 MHz, CDCl3) delta-58.04; EIMS m/z 307 ([M]+).
With hydrogenchloride; In N,N-dimethyl-formamide; Example 5 Preparation of 3-bromo-1-(4-(trifluoromethoxy)Phenyl)-1H-1,2,4-triazole A dry round bottom flask was charged with potassium phosphate (K3PO4, 7.74 g, 36.5 mmol), CuI (0.165 g, 0.868 mmol), and <strong>[7343-33-1]3-bromo-1H-1,2,4-triazole</strong> (2.83 g, 19.10 mmol). The flask was evacuated/backfilled with N2 (3*). DMF (34.7 mL) was added, followed by trans-(1R,2R)-N,N'-bismethyl-1,2-cyclohexane diamine (0.274 mL, 1.736 mmol) and 1-iodo-4-(trifluoromethoxy)benzene (5 g, 17.36 mmol). The solution was heated to 110° C. After 48 h, the reaction mixture was cooled to RT, diluted with EtOAc and filtered through Celite®. The filtrate was washed with water (100 mL) containing HCl (1 M, 10 mL). The organics were separated, and the aqueous phase was further extracted with EtOAc (3*). The organics were combined, dried with sodium sulfate, and concentrated in vacuo. Purification via flash column chromatography (EtOAc/hexanes) yielded the title compound as a tan solid (1.86 g, 34percent): 1H NMR (400 MHz, CDCl3) delta 8.44 (s, 1H), 7.70 (d, J=8.9 Hz, 2H), 7.38 (d, J=8.5 Hz, 2H); 19F NMR (376 MHz, CDCl3) delta-58.04; EIMS m/z 307 ([M]+).
  • 20
  • [ 7343-33-1 ]
  • [ 824-94-2 ]
  • 5-bromo-1-(4-methoxybenzyl)-1H-[1,2,4]triazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
20% With N-ethyl-N,N-diisopropylamine; potassium iodide; In acetonitrile; for 2h;Reflux; 5-Bromo-l-(4-methoxy-benzyl)-lH-[l,2 4]triazole In a 100 mL round-bottomed flask, 3-bromo-lH-l,2,4-triazole (3 g, 20.3 mmol, Eq: 1.00), 1- (chloromethyl)-4-methoxybenzene (3.18 g, 20.3 mmol, Eq: 1) and N-ethyl-N-isopropylpropan-2- amine (5.24 g, 40.6 mmol, Eq: 2) were combined with acetonitrile (101 ml) to give a light yellow solution. Potassium iodide (1.68 g, 10.1 mmol, Eq: 0.5) was added. The mixture was heated to reflux for 2 hours. The mixture was cooled down and poured into water (50 mL) and extracted with EtOAc (3x50 mL), the combined extracts were washed with water (50 mL) and brine (50 mL), dried over anhydrous Na2S04, concentrate to afford the crude product. Purify the compound by column chromatography (hexanes/ EtOAc = 70/30) to afford the oil 1.1 g (20percent).
  • 21
  • [ 7343-33-1 ]
  • [ 135049-82-0 ]
  • 3-bromo-1-(4-isopropoxyphenyl)-1H-1,2,4-triazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
23% With copper(l) iodide; caesium carbonate; In dimethyl sulfoxide; at 100℃; for 20h;Inert atmosphere; Example 1Preparation of 3-bromo-1-(4-isopropoxyphenyl)-1H-1,2,4-triazole <strong>[7343-33-1]3-bromo-1H-1,2,4-triazole</strong> (1.75 g, 11.8 mmol), copper(I) iodide (0.370 g, 1.94 mmol), cesium carbonate (4.98 g, 15.3 mmol), and 1-iodo-4-isopropoxybenzene (2.04 g, 7.78 mmol) (Katsumatu, T., et al. Macromolecular Chemistry and Physics, 2009, 210 (22), 1891-1902) was placed in dimethylsulfoxide (50 mL) and degassed with nitrogen for 10 minutes. The solution was heated at 100° C. for 20 hours. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate and filtered through Celite®. The resulting filter cake was rinsed with additional ethyl acetate (100 mL). The filtrate was washed with water (2*50 mL). The combined aqueous washes were neutralized with hydrochloric acid (2 N) as measured by pH paper. The aqueous solution was extracted with ethyl acetate (2*30 mL) and the organic extracts were combined, and then dried over anhydrous magnesium sulfate. The organic solution was concentrated onto Celite® and purified by silica gel chromatography using 0-100percent ethyl acetate/hexanes as eluent. The relevant fractions were concentrated to obtain the title compound as a yellow oil (0.540 g, 23percent): 1H NMR (400 MHz, CDCl3) delta 8.31 (s, 1H), 7.51 (d, J=9.1 Hz, 2H), 6.98 (d, J=9.0 Hz, 2H), 4.59 (p, J=6.1 Hz, 1H), 1.36 (d, J=6.1 Hz, 6H); ESIMS m/z 283 ([M+H]+).
  • 22
  • [ 7343-33-1 ]
  • 2-[6-chloro-3-(ethanesulfonyl)pyridin-2-yl]-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine [ No CAS ]
  • C17H13BrF3N7O2S [ No CAS ]
YieldReaction ConditionsOperation in experiment
370 mg With potassium carbonate; In N,N-dimethyl-formamide; for 2.5h;Cooling with ice; 2- [6-Chloro-3- (ethanesulfonyl) pyridin-2-yl] -3-methyl-6- (trifluoromethyl)-3H-imidazo [4,5-b] 300mg, potassium carbonate 133 mg, and to a mixture of 3 mL of DMF, was added <strong>[7343-33-1]3-bromo-1H-1,2,4-triazole</strong> 132mg under ice-cooling. After the mixture was stirred under ice-cooling for 2.5 hours, a saturated aqueous solution layer was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, and saturated brine, and dried with anhydrous sodium sulfate. The resulting organic layer was dried under reduced pressure. The resulting residue was subjected to silica gel chromatography to obtain 370mg of the compound of the present invention beta3 referred to below.
370 mg With potassium carbonate; In N,N-dimethyl-formamide; for 2.5h;Cooling with ice; 2 - (6 - chloro - 3 - ethanesulfonyl - pyridin - 2 - yl) - 3 - methyl - 6 - trifluoromethyl - 3 H - imidazo [4,5 - b] pyridine300 mg,Potassium carbonate133 mg, and N, N-dimethylformamide 3 mL, 3-boule132 mg of lomo-1 H-1,2,4-triazole was added. And the mixture was stirred for 2.5 hours under ice coolingAfter that, a saturated multilayer aqueous solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. Water and saturated organic layerWashed with Japanese salt water, and dried with anhydrous sodium sulfate. The obtained organic layer was dried under reduced pressure.The obtained residue was subjected to silica gel chromatography, and the following compound 3 described below was separated by 370 mg.
370 mg With potassium carbonate; In N,N-dimethyl-formamide; at 0℃; for 2.5h; To a mixture of the intermediate 5 300 mg, potassium carbonate 133 mg and N,N-dimethylformamide 3 mL was added <strong>[7343-33-1]3-bromo-1H-1,2,4-triazole</strong> 132 mg at 0°C. The mixtures were stirred at 0°C for 2.5 hours and to the reaction mixture was added saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The organic layers were washed with water and brine and dried over anhydrous sodium sulfate. The resulting organic layers were concentrated under reduced pressure. The resulting residues were subjected to a silica gel column chromatography to give the following present compound 3 370 mg. H1-NMR (CDCl3) delta: 9.04 (1H, s), 8.81 (1H, br s), 8.73 (1H, d), 8.35 (1H, br s), 8.26 (1H, d), 3.92 (3H, s), 3.81 (2H, q), 1.39 (3H, t).
370 mg With potassium carbonate; In N,N-dimethyl-formamide; for 2.5h;Cooling with ice; 300 mg of Intermediate 4, 133 mg of potassium carbonate,And 3 mL of DMF was added 132 mg of 3-bromo-1 H-1,2,4-triazole under ice cooling.After stirring for 2.5 hours under ice cooling,Saturated multilayer aqueous solution was added to the reaction mixture,And extracted with ethyl acetate. The organic layer was washed with water,And washed with saturated brine,And dried over anhydrous sodium sulfate.The obtained organic layer was dried under reduced pressure.The obtained residue was subjected to silica gel chromatography,370 mg of the present compound 12 described below was obtained.

  • 23
  • [ 7343-33-1 ]
  • 2-[6-chloro-3-(ethanesulfonyl)pyridin-2-yl]-3-methyl-6-[(trifluoromethyl)sulfanyl]-3H-imidazo[4,5-b]pyridine [ No CAS ]
  • C17H13BrF3N7O2S2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
83 mg With sodium hydride; In N,N-dimethyl-formamide; mineral oil; for 2.5h;Cooling with ice; 2- [6-Chloro-3- (ethanesulfonyl) pyridin-2-yl] -3-methyl-6 - [(trifluoromethyl) sulfanyl]-3H-imidazo [4,5-b] pyridine 200 mg, 60percent sodium hydride (oily) 54 mg, and a mixture of 1 ml DMF, was added <strong>[7343-33-1]3-bromo-1H-1,2,4-triazole</strong> 198mg under ice-cooling. After the mixture was stirred under ice-cooling for 2.5 hours, a saturated aqueous solution layer was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, and saturated brine, and dried with anhydrous sodium sulfate. The resulting organic layer was dried under reduced pressure. The resulting residue was subjected to silica gel chromatography to obtain 83mg of the present invention of compounds beta39 that described below.
83 mg With sodium hydride; In N,N-dimethyl-formamide; mineral oil; for 2.5h;Cooling with ice; 200 mg of intermediate 35, 60percent sodium hydride(Oily), and 1 mL of DMF,Under ice-cooling, 198 mg of <strong>[7343-33-1]3-bromo-1H-1,2,4-triazole</strong> was added. After stirring for 2.5 hours under ice cooling,Saturated multilayer aqueous solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine,And dried over anhydrous sodium sulfate. The obtained organic layer was dried under reduced pressure. The obtained residue was subjected to silica gel chromatography,83 mg of the present invention compound 245 described below was obtained.
  • 24
  • [ 7343-33-1 ]
  • [ 156545-07-2 ]
  • 3-bromo-1-(3,5-difluorophenyl)-1,2,4-triazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
50% With pyridine; copper diacetate; In dichloromethane; at 20℃; for 72h;Molecular sieve; Method 1: Diacetoxycopper (2.30 g, 12.7 mmol), 3,5-difluorophenyl-boronic acid (1.60 g, 10.1 mmol), <strong>[7343-33-1]3-bromo-1H-1,2,4-triazole</strong> (1.25 g, 8.4 mmol) and 4A molecular sieve (150mg) were mixed in DCM (50 mL), and pyridine (1.3 mL, 16.90 mmol) was added. The mixture was stined at RT under air for 3 days. LCMS showed that no starting material remained and desired product was formed. The reaction was filtered through a plug of Celite via suction and the solid was washed with additional DCM (200m1). The combined organic layer was washed with 0.1 N aqueous HC1 three times (50 ml x 3) and brine (200 ml). The organic layer was concentrated and purified on silica gel (120 g column, dry loading method on Celite) using 10-90percent EtOAc:Hexanes to afford 1.23 g (50percent) of desired product JW-lc. ?H NMR (400 MHz, DMSO-d6) oe 9.40 (s, 1H), 7.78 - 7.61 (m, 2H), 7.41 (tt, J = 9.3, 2.3 Hz, 1H) ppm. ESI-MS m/z calc. 258.95566, found 260.05 (M+1)+; Retention time: 0.8 minutes.
  • 25
  • [ 7343-33-1 ]
  • [ 768-35-4 ]
  • 3-bromo-1-(3-fluorophenyl)-1,2,4-triazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
38% With pyridine; copper diacetate; In dichloromethane; at 20℃; for 72h; <strong>[7343-33-1]3-bromo-1H-1,2,4-triazole</strong> (9.6 g, 64.9 mmol), pyridine (10.5 mL, 129.8 mmol), copper (II) acetate (17.7 g, 97.3 mmol) and (3-fluorophenyl) boronic acid (11.4 g, 81.1 mmol) were mixed in DCM (200 mL) and the reaction was stined at room temperature for 3 days. The solid was filtered off and the filtrate was washed with water several times. The organic layer was dried, concentrated and purified on silica gel to afford 6.3 g of desired product JW-2c in 38percent yield. ?H NMR (400 MHz, CDC13) oe 8.45 (s, 1H), 7.54 - 7.47 (m, 1H), 7.45 (t, J = 7.5 Hz, 2H), 7.20 - 7.04 (m, 1H) ppm. ESI-MS m/z calc. 240.96509, found 242.27 (M+1)+; Retention time:0.75 minutes.
  • 26
  • [ 7343-33-1 ]
  • [ 168267-41-2 ]
  • 3-bromo-1-(3,4-difluorophenyl)-1,2,4-triazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
60% With pyridine; copper diacetate; In dichloromethane; at 20℃; for 72h;Molecular sieve; Diacetoxycopper (18.4 g, 101.4 mmol), bromo-triazole (lOg, 67.6 mmol), and 4A molecular sieves (250 mg, 0.33 mmol) were mixed in DCM, to which 4-difluorophenyl)boronic acid (14.9g, 94.6 mmol), pyridine (10.9 mL, 135.2 mmol) was added. The mixture was stined at RT under air for 3 days. LCMS showed that no starting material remaining and desired product was formed. The reaction was filtered and the solid was washed with additional DCM (200 ml). The combined organic layer was concentrated with silica gel and dry-loaded to purify on silica gel (240 grams column, 10-90percent ethyl acetate:hexanes) to afford 10.5 g (60percent) of desired product JW3-c. ?H NMR (400 MHz, DMSO-D6) oe 9.30 (s, 1H), 8.08 - 7.96 (m, 1H), 7.77 - 7.62 (m, 2H) ppm. ESI-MS m/z calc. 25 8.95566, found 260.32 (M+1)+; Retention time: 0.96 minutes.
54% With pyridine; In dichloromethane; at 20℃; for 72h;Molecular sieve; Copper(II) acetate (approximately 18.42 g, 101.4 mmol), <strong>[7343-33-1]3-bromo-1H-1,2,4-triazole</strong> (10 g, 67.59 mmol), and 4 A molecular sieves (250 mg/0.33 mmol) were combined in dichloromethane and treated with 3,4-difluorophenyl boronic acid (14.94 g, 94.63 mmol), and pyridine (approximately 10.69 g, 10.93 mL, 135.2 mmol). The mixture was stirred at room temperature under air for 3 days. The reaction was filtered and the solid was washed with additional dichloromethane (200 mL). The combined organic layers were concentrated with silica gel and dry-loaded to purify on silica gel to afford 3-bromo-1-(3,4-difluorophenyl)-1,2,4-triazole (10.5 g, 54percent). MR (400 MHz, DMSO-^e) delta 9.30 (s, 1H), 8.08 - 7.96 (m, 1H), 7.77 - 7.62 (m, 2H) ppm. ESI-MS m/z calc. 258.95566, found 260.32 (M+l)+; Retention time: 0.96 minutes.
  • 27
  • [ 7343-33-1 ]
  • [ 367-23-7 ]
  • 3-bromo-1-(2,5-difluorophenyl)-1,2,4-triazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
25% With potassium carbonate; In N,N-dimethyl-formamide; at 100 - 110℃; for 22h; [004581 Combined 3 -bromo- 1 H-i ,2,4-triazole (29.6 g, 200 mmol), 1,2 ,4-trifluorobenzene(79.3 g, 62.70 mL, 600.0 mmol) and potassium carbonate (27.6 g, 200.0 mmol) in 500mL of DMF and heated to i000ii00 for 22 hours. The mixture was cooled and DMF removed under vacuum to dryness. 250 mL of water was added and the organics extracted with EtOAc. The organic layer was dried over sodium sulfate, filtered and evaporated. The crude mixture was purified on silica gel (220 grams column, 10-50percent Ethyl acetate:Hexanes) to afford 13g (25percent) of product JW-4c as off white solid. ?H NMR (300 MHz, DMSO-d6) oe 9.10 (d, J = 2.0 Hz, 1H), 7.77 (ddd, J = 8.9, 5.9, 3.2 Hz, 1H), 7.65 (ddd, J = 10.4, 9.3, 4.8 Hz, 1H), 7.52 - 7.41 (m, 1H) ppm. ESI-MS m/z calc. 258.95566, found 260.01 (M+i)+; Retention time: 0.79 minutes.
  • 28
  • [ 7343-33-1 ]
  • [ 98-80-6 ]
  • [ 56617-00-6 ]
YieldReaction ConditionsOperation in experiment
38% With pyridine; copper diacetate; In dichloromethane; at 20℃;Molecular sieve; 3-Bromo-1H-1,2,4-triazole (3 g, 20.28 mmol), copper (II) acetate (7.37 g, 40.56 mmol), phenylboronic acid (4.945 g, 40.56 mmol), pyridine (3.208 mL, 40.56 mmol), and crushed and activated 4 A molecular sieves (15 g) were combined in a 1000 mL round bottom flask. The mixture was diluted with dichloromethane (300 mL), and stirred over the weekend with the cap loose at room temperature. The reaction mixture was filtered through Celite and washed with methanol (approximately 100 mL). Celite was added and the mixture was concentrated to dryness under reduced pressure and purified by silica gel chromatography (80 gram Gold column (ISCO); 0-100percent ethyl acetate/hexane). Possible regioisomer observed in 1H NMR and in LC/MS (impurity runs faster). No separation on normal phase. Combined the desired fractions and concentrated to dryness under reduced pressure. The enriched material was diluted with dimethylsulfoxide and purified by reverse phase chromatography (275 gram Gold C-18 column (ISCO); 10-100percent acetonitrile/water with trifluoroacetic acid modifier). The pure fractions were concentrated to dryness under reduced pressure to give 3-bromo-1-phenyl-1,2,4- triazole (1.72 g, 38percent). 1H NMR (400 MHz, OMSO-de) delta 9.31 (s, 1H), 7.88 - 7.76 (m, 2H), 7.65 - 7.52 (m, 2H), 7.46 (t, J = 7.4 Hz, 1H) ppm. ESI-MS m/z calc. 222.9745, found 223.97 (M+l)+; Retention time: 2.66 minutes.
34% With pyridine; copper diacetate; In dichloromethane; at 20℃; for 240h;Molecular sieve; To a suspension of 3-bromo-1H-i,2,4-triazole (lOg, 67.6mM) and phenylboronic acid (16.5g, 135.2mM) in 500 mL of DCM, was added the following: pyridine; (i0.9mL, i0.7g, 135.2mM), copper (II) acetate; (1 8.4g, 101.5mM) and powdered 4A molecular sieves (45g). The resulting blue colored suspension was stined at room temperature for 10 days open to the air. Additional DCM (500mL) was added to the reaction and the mixture filtered through a pad of diatomaceous earth, washing the cake with DCM, 10percent MeOH/DCM, and finally DCM. The filtrates were collected and concentrated under reduced pressure to provide a viscous residue, which was partitioned between ethyl acetate and iN HC1. The organic phase was washed with water (2x), brine (ix) then dried over anhydrous sodium sulphate. Suction filtered the organic layer to remove particulates and evaporated under reduced pressure to give the crude product which was purified on CombiFlash (240g column) 5i02 eluting with 25percent ethyl acetate /heptanes. Combined clean fractions and reduced the volume of the fractions under reduced pressure until crystals formed. Isolated crystals via suction filtration, washed with additional heptanes and air dried to yield 3-bromo-i-phenyl-1H-i,2,4-triazole as a white crystalline solid (5.ig, 34percent yield). ?H NMR (400 MHz, DMSO-d6) oe 9.32(s, 1H), 7.92 - 7.79 (m, 2H), 7.58 (dd, J=ii.3, 4.5Hz, 2H), 7.51-7.41 (m, 1H) ppm. ESI-MS m/z calc. 222.9745, found 224.0 (M+i)+; Retention time: 0.75 minutes.
  • 29
  • [ 7343-33-1 ]
  • [ 491862-84-1 ]
  • 3-bromo-1-(3-fluoro-5-methylphenyl)-1H-1,2,4-triazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
26.6% With copper(l) iodide; caesium carbonate; In dimethyl sulfoxide; at 100℃; for 20h;Inert atmosphere; [00464j To a 1OOml flask was added 3-bromo-1H-i,2,4-triazole (739.8 mg, 5 mmol), CuT (95.2 mg, 0.50 mmol) and Cs2C03 (1.629 g, 5.0 mmol) and the flask was evacuated thenbackfilled with N2 before adding DMS0 (5 mL) and i-fluoro-3-iodo-5-methyl-benzene (590.1 mg, 2.50 mmol). The reaction mixture was heated at 100°C for 20h at which time LCMSindicated the major peak was desired product. To the reaction mixture was added Et0Ac, the mixture was filtered through celite and to the filtrate was added brine. The organic phase wasdried over MgS04, filtered, evaporated to dryness and purified on an Isco 40g silica gel column eluting with heptanes and ethyl acetate to afford 3-bromo-i-(3-fluoro-5-methyl-phenyl)-i,2,4-triazole HG-3a (170 mg, 26.6percent). ?H NMR (300 MHz, CDC13) oe 8.43 (s, 1H), 7.29 (d, J = 2.7 Hz, 1H), 7.23 (dt, J = 9.0, 2.0 Hz, 1H), 6.97 (d, J = 9.1 Hz, 1H), 2.46 (s, 3H)ppm. ESI-MS m/z calc. 254.98074, found 257.97 (M+i) Retention time: 0.81 minutes.
  • 30
  • [ 14508-49-7 ]
  • [ 7343-33-1 ]
  • 2-(3-bromo-1,2,4-triazol-1-yl)pyrazine [ No CAS ]
YieldReaction ConditionsOperation in experiment
83.8% With potassium carbonate; In 1-methyl-pyrrolidin-2-one; at 125℃; for 6h; A mixture of K2C03 (29.19 g, 211.2 mmol), <strong>[7343-33-1]3-bromo-1H-1,2,4-triazole</strong> (25 g, 169.0 mmol) and 2-chloropyrazine (19.36 g, 169.0 mmol) inNMP (130 mL) was heated at 125 °C for 6 hrs. The reaction was quenched with water (300 mL) and stined for lh. The solids were collected, washed with water, ether and dried to give 2-(3-bromo-1,2,4-triazol-1-yl)pyrazine (32 g, 83.8percent). ?H NMR (300 MHz, CD3OD+CDC13) oe 9.40 - 9.05 (m, 2H), 8.70 (d, J = 2.5 Hz, 1H), 8.56 (dd, J = 2.5, 1.5 Hz, 1H) ppm. ESI-MS m/z calc. 224.97, found 226.29 (M+1)+; Retention time: 0.75 minutes
  • 31
  • [ 7343-33-1 ]
  • [ 888327-36-4 ]
  • 2-(3-bromo-1H-1,2,4-triazol-1-yl)-5-(trifluoromethoxy)pyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
31% With copper(l) iodide; caesium carbonate; In N,N-dimethyl-formamide; at 100℃; for 1h;Inert atmosphere; Microwave irradiation; Example 2 Preparation of 2-(3-bromo-1H-1,2,4-triazol-1-yl)-5-(trifluoromethoxy)pyridine (C2) To a reaction vial were added 2-bromo-5-(trifluoromethoxy)pyridine (1.0 g, 4.1 mmol) and <strong>[7343-33-1]3-bromo-1H-1,2,4-triazole</strong> (0.91 g, 6.2 mmol). N,N-Dimethylformamide (16 mL) and cesium carbonate (2.6 g, 8.2 mmol) were added, and the vial was degassed for 5 minutes with argon. Copper(I) iodide (0.077 g, 0.41 mmol) was added, and the vial was further degassed for 5 minutes with argon. The vial was capped and heated at 100 C. for 1 hour in a Biotage Initiator microwave reactor, with external IR-sensor temperature monitoring from the side of the vessel. The reaction mixture was cooled to room temperature, poured onto crushed ice (3 volumes), and extracted with ethyl acetate (3*150 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated. Purification by flash column chromatography using 0-40% ethyl acetate/hexanes as eluent provided the title compound as a pale brown liquid (0.40 g, 31%): 1H NMR (400 MHz, CDCl3) delta 9.01 (s, 1H), 8.39 (d, J=2.4 Hz, 1H), 7.94 (d, J=8.8 Hz, 1H), 7.77 (dd, J=1.6 Hz, 8.8 Hz, 1H); ESIMS m/z 309 ([M+H]+).
31% With copper(l) iodide; caesium carbonate; In N,N-dimethyl-formamide; at 100℃; for 1h;Sealed tube; Microwave irradiation; To a reaction vial were added 2-bromo-5-(trifluoromethoxy)pyridine ( 1.0 g, 4.1 mmol) and 3-bromo- l - -l,2,4-triazole (0.91 g, 6.2 mmol). Lambda ,/V-Dimethylformamide (16 ml_) and cesium carbonate (2.6 g, 8.2 mmol) were added, and the vial was degassed for 5 minutes with argon. Copper(I) iodide (0.077 g, 0.41 mmol) was added, and the via l was further degassed for 5 minutes with argon. The vial was capped and heated at 100 C for 1 hour in a Biotage Initiator microwave reactor, with external IR-sensor temperature monitoring from the side of the vessel. The reaction mixture was cooled to room temperature, poured onto crushed ice (3 volumes), and extracted with ethyl acetate (3 x 150 ml_). The combined organic layers were dried over sodium sulfate, filtered, and concentrated. Purification by flash column chromatography using 0-40% ethyl acetate/hexanes as eluent provided the title compound as a pale brown liquid (0.40 g, 31%) : *H N MR (400 MHz, CDCI3) delta 9.01 (s, 1H), 8.39 (d, J = 2.4 Hz, 1H), 7.94 (d, J = 8.8 Hz, 1H), 7.77 (dd, J = 1.6 Hz, 8.8Hz, 1H) ; ESIMS m/z 309 ([M + H]+).
  • 32
  • [ 7343-33-1 ]
  • [ 115519-20-5 ]
  • 3-bromo-1-(4-(trifluoromethoxy)phenethyl)-1H-1,2,4-triazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
36% With caesium carbonate; In acetonitrile; at 20 - 24℃; for 72h; To a suspension of <strong>[7343-33-1]3-bromo-1H-1,2,4-triazole</strong> (0.500 g, 3.38 mmol) and cesium carbonate (1.10 g, 3.38 mmol) in acetonitrile (6.8 mL) was added 1-(2-bromoethyl)-4- (trifluoromethoxy)benzene (0.909 g, 3.38 mmol). The reaction mixture was stirred at room temperature for 3 days. The solution was diluted with dichloromethane andwashed with water. The organic extracts were washed with brine, dried, filtered, and concentrated. Purification by flash column chromatography using 0-100percent ethyl acetate/hexanes as eluent provided the title compound as a colorless oil (0.410 g, 36percent): 1H NMR (400 MHz, CDCI3) O 7.66 (s, 1H), 7.15 (dq, J = 7.7, 1.0 Hz, 2H), 7.12 -7.04 (m, 2H), 4.39 - 4.28 (m, 2H), 3.19 (t, J = 7.0 Hz, 2H); 19 NMR (376 MHz, CDCI3)O -57.93; ESIMS m/z 337 ([M+H]).
  • 33
  • [ 7343-33-1 ]
  • [ 461-17-6 ]
  • 3-bromo-1-(4,4,4-trifluorobutyl)-1H-1,2,4-triazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
37% With caesium carbonate; In acetonitrile; at 20 - 24℃; for 72h; To a suspension of <strong>[7343-33-1]3-bromo-1H-1,2,4-triazole</strong> (5.0 g, 34 mmol) and cesiumcarbonate (11 g, 34 mmol) in acetonitrile (50 mL) was added 1,1,1-trifluoro-4-iodobutane (6.8 mL, 34 mmol). The solution was stirred at room temperature for 72 hours. The solution was poured into water (50 mL) and extracted with diethyl ether (2 x 100 mL). The combined organic layers were concentrated. Purification by flash column chromatography using 0-20percent ethyl acetate/hexanes as eluent, provided the titlecompound as a 70:30 mixture of isomers (3.2 g, 37percent). The mixture was used in the next step without further purification: 1H NMR (400 MHz, CDCI3) O 7.96 (s, 1H), 4.22 (t, J = 6.5 Hz, 2H), 2.27 ? 2.07 (m, 4H); 19 NMR (376 MHz, CDCI3) O -65.83.
  • 34
  • [ 252947-01-6 ]
  • [ 7343-33-1 ]
  • 3-bromo-1-(4,4,5,5,5-pentafluoropentyl)-1H-1,2,4-triazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
49% With caesium carbonate; In acetonitrile; at 20 - 24℃; for 72h; To a suspension of <strong>[7343-33-1]3-bromo-1H-1,2,4-triazole</strong> (5.0 g, 34 mmol) and cesiumcarbonate (11 g, 34 mmol) in acetonitrile (50 mL) was added 1,1,1-trifluoro-4-iodobutane (6.8 mL, 34 mmol). The solution was stirred at room temperature for 72 hours. The solution was poured into water (50 mL) and extracted with diethyl ether (2 x 100 mL). The combined organic layers were concentrated. Purification by flash column chromatography using 0-20percent ethyl acetate/hexanes as eluent, provided the titlecompound as a 70:30 mixture of isomers (3.2 g, 37percent). The mixture was used in the next step without further purification; Prepared using 4,4,5,5,5-pentafluoropentyl methanesulfonate and isolated as a light-brown liquid (3.5 g, 49percent): 1H NMR (400 MHz, CDCI3) O 7.90 (s, 1H), 4.32 - 4.30 (m, 2H), 2.27 - 2.00 (m, 4H); ESIMS m/z 308 ([M+H]).
  • 35
  • [ 7343-33-1 ]
  • [ 32315-10-9 ]
  • (R)-6-((benzyloxy)methyl)-1,2,3,6-tetrahydropyridine [ No CAS ]
  • (R)-(6-((benzyloxy)methyl)-3,6-dihydropyridin-1(2H)-yl)(3-bromo-1H-1,2,4-triazol-1-yl)methanone [ No CAS ]
 

Historical Records

Technical Information

Categories

Related Functional Groups of
[ 7343-33-1 ]

Bromides

Chemical Structure| 389122-08-1

A140898 [389122-08-1]

5-Bromo-1H-1,2,4-triazol-3-amine

Similarity: 0.84

Chemical Structure| 7411-23-6

A153419 [7411-23-6]

3,5-Dibromo-1H-1,2,4-triazole

Similarity: 0.82

Chemical Structure| 16681-72-4

A114429 [16681-72-4]

5-Bromo-1-methyl-1H-1,2,4-triazole

Similarity: 0.78

Chemical Structure| 23579-79-5

A185259 [23579-79-5]

3,5-Dibromo-1-methyl-1H-1,2,4-triazole

Similarity: 0.66

Chemical Structure| 56616-91-2

A215472 [56616-91-2]

3-Bromo-1-methyl-1H-1,2,4-triazole

Similarity: 0.58

Related Parent Nucleus of
[ 7343-33-1 ]

Triazoles

Chemical Structure| 389122-08-1

A140898 [389122-08-1]

5-Bromo-1H-1,2,4-triazol-3-amine

Similarity: 0.84

Chemical Structure| 7411-23-6

A153419 [7411-23-6]

3,5-Dibromo-1H-1,2,4-triazole

Similarity: 0.82

Chemical Structure| 16681-72-4

A114429 [16681-72-4]

5-Bromo-1-methyl-1H-1,2,4-triazole

Similarity: 0.78

Chemical Structure| 23579-79-5

A185259 [23579-79-5]

3,5-Dibromo-1-methyl-1H-1,2,4-triazole

Similarity: 0.66

Chemical Structure| 288-88-0

A234123 [288-88-0]

1H-1,2,4-Triazole

Similarity: 0.65