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Chemical Structure| 380380-60-9 Chemical Structure| 380380-60-9

Structure of 380380-60-9

Chemical Structure| 380380-60-9

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Product Details of [ 380380-60-9 ]

CAS No. :380380-60-9
Formula : C6H4BrN5
M.W : 226.03
SMILES Code : BrC1=CN=C(C=C1)C1=NN=NN1
MDL No. :MFCD08062726
InChI Key :LBDJSOHAVRCQPD-UHFFFAOYSA-N
Pubchem ID :23438683

Safety of [ 380380-60-9 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H315-H319-H228
Precautionary Statements:P240-P210-P241-P264-P280-P302+P352-P370+P378-P337+P313-P305+P351+P338-P362+P364-P332+P313
Class:4.1
UN#:1325
Packing Group:

Computational Chemistry of [ 380380-60-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 11
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 4.0
Num. H-bond donors 1.0
Molar Refractivity 45.11
TPSA ?

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

67.35 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.35
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

0.87
Log Po/w (WLOGP)?

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

1.02
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.

0.99
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

1.82
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.21

Water Solubility

Log S (ESOL):?

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

-2.4
Solubility 0.896 mg/ml ; 0.00396 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.

-1.87
Solubility 3.06 mg/ml ; 0.0135 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

-3.5
Solubility 0.0723 mg/ml ; 0.00032 mol/l
Class?

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

Soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

High
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

No
P-gp substrate?

P-glycoprotein substrate: SVM model built on 1033 molecules (training set)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

No
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-7.06 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

0.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.56

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)

2.0

Application In Synthesis of [ 380380-60-9 ]

* 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 [ 380380-60-9 ]

[ 380380-60-9 ] Synthesis Path-Downstream   1~17

  • 1
  • [ 380380-60-9 ]
  • [ 74-88-4 ]
  • [ 380380-64-3 ]
  • [ 380380-63-2 ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; In DMF (N,N-dimethyl-formamide); at 0 - 20℃; for 2h; 5-Bromo-2-(2-methyl-2H-tetrazol-5-yl) pyridine and 5-bromo-2- (1-methyl-1H-tetrazol-5- yl) pyridine. 5-Bromo-2-(2-methyl-2H-tetrazol-5-yl)pyridine and 5-bromo-2-(1-methyl-1H-tetrazol-5- yl) pyridine were prepared according to the procedure described by Dong A Pharmaceuticals (WO 01/94342). A mixture of 6.5 g unpurified 5-bromo-2-tetrazol-5-ylpyridine [Dong A Pharmaceuticals (WO 01/94342) ] (~28 mmol) and sodium hydroxide (9 g, 125 mmol) in dry dmf was evaporated to dryness under reduced pressure. A stirred solution of the involatile residue in dry DMF (50 mL) was treated dropwise at ice-bath temperature with iodomethane (3.0 ML, 48 mmol). The stirred reaction mixture was allowed to warm and then maintained at room temperature for 2 hours. The reaction mixture was partitioned between iced water and ethyl acetate. The organic phase was washed with water, dried over magnesium sulfate, and tehn evaporated under reduced pressure to give a residue that was purified by chromatography on silica gel [elution with dichloromethane : ethyl acetate (60: 1) ] to give: 1. 5-bromo-2- (1-methyl-1H-tetrazol-5-yl)pyridine (1.397 g), a colorless solid, (TLC: silica-gel, hexanes: ethyl acetate (4: 1), Rf: 0. 3), 1H-NMR (DMSO-d6) (300 MHz) 8 : 4.38 (s, 3H); 8.17 (d, 1H); 8.35 (dd, 1H); 8.96 (d, 1H). 2. 5-bromo-2-(2-methyl-2H-tetrazol-5-yl)pyridine (1.07 g), a colorless solid, (TLC: silica-gel, hexanes: ethyl acetate (4: 1), Rf : 0. 1). 1H-NMR (DMSO-d6) (300 MHz) No. : 4.46 (s, 3H); 8.09 (d, 1H) ; 8.28 (dd, 1H) ; 8.88 (d, 1H).
With sodium hydroxide; In DMF (N,N-dimethyl-formamide); at 0 - 20℃; for 2h; 5-BROMO-2- (2-METHYL-2H-TETRAZOL-5-YL) PYRIDINE AND 5-BROMO-2- (L-METHYL-LH-TETRAZOL-5- YL) pyridine 5-Bromo-2-(2-methyl-2H-tetrazol-5-yl) pyridine and 5-BROMO-2- (1-METHYL-LH-TETRAZOL-5- YL) pyridine were prepared according to the procedure described by Dong A Pharmaceuticals (WO 01/94342). A mixture of 6.5 g unpurified <strong>[380380-60-9]5-BROMO-2-TETRAZOL-5-YLPYRIDINE</strong> [Dong A Pharmaceuticals (WO 01/94342)] (-28 mmol) and sodium hydroxide (9 g, 125 mmol) in dry DMF was evaporated to dryness under reduced pressure. A stirred solution of the involatile residue in dry DMF (50 ML) was treated dropwise at ice-bath temperature with iodomethane (3.0 mL, 48 mmol). The stirred reaction mixture was allowed to warm and then maintained at room temperature for 2 hours. The reaction mixture was partitioned between iced water and ethyl acetate. The organic phase was washed with water, dried over magnesium sulfate, and tehn evaporated under reduced pressure to give a residue that was purified by chromatography on silica gel [elution with dichloromethane : ethyl acetate (60: 1) ] to give: 1. 5-bromo-2-(1-methyl-1H-tetrazol-5-yl) pyridine (1.397 g), a colorless solid, (TLC: silica-gel, hexanes: ethyl acetate (4: 1), Rf: 0.3),'H-NMR (DMSO-D) (300 MHz) 8 : 4.38 (s, 3H); 8.17 (d, 1H); 8.35 (dd, 1H); 8.96 (d, 1H). 2. 5-bromo-2-(2-methyl-2H-tetrazol-5-yl) pyridine (1.07 g), a colorless solid, (TLC: silica-gel, hexanes: ethyl acetate (4: 1), Rf: 0. 1). LH-NMR (DMSO-DSLT300 MHz) 8 4.46 (s, 3H); 8.09 (d, 1H); 8.28 (dd, 1H) ; 8.88 (d, 1H). Structure assignment based on nmr HMBC experiments, in which long range coupling of the protons of CH3 to the C5 of the tetrazole ring is observed in the 1-methyl-1H-isomer of Rf 0.3, but not in the 2-methyl-2H-isomer of Rf 0.1). The compound referred to as 5-bromo-2- (1-METHYL-LH-TETRAZOL-5-YL) pyridine is thus the isomer of Rf 0.3 and the compound referred to as 5-BROMO-2-(2-METHYL-2H-TETRAZOL-5-YL) PYRIDINE is thus the ISOMER OF RF 0. 1
With sodium hydroxide; In DMF (N,N-dimethyl-formamide); at 0 - 20℃; for 2h; 5-BROMO-2-(2-METHYL-2H-TETRAZOL-5-YL) PENDINE AND 5-BROMO-2-(1-METHEL-LH-TETRAZOL-5- 1 pyridine 5-BROMO-2- (2-METHYL-2H-TETRAZOL-5-YL) PYRIDINE AND 5-BROMO-2- (L-METHYL-LH-TETRAZOL-5- yl) pyridine were prepared according to the procedure described by Dong A Pharmaceuticals (WO 01/94342). A mixture of 6.5 g unpurified <strong>[380380-60-9]5-BROMO-2-TETRAZOL-5-YLPYRIDINE</strong> [Dong A Pharmaceuticals (WO 01/94342)] (-28 mmol) and sodium hydroxide (9 g, 125 mmol) in dry DMF was evaporated to dryness under reduced pressure. A stirred solution of the involatile residue in dry DMF (50 ML) was treated dropwise at ice-bath temperature with iodomethane (3.0 mL, 48 mmol). The stirred reaction mixture was allowed to warm and then maintained at room temperature for 2 hours. The reaction mixture was partitioned between iced water and ethyl acetate. The organic phase was washed with water, dried over magnesium sulfate, and tehn evaporated under reduced pressure to give a residue that was purified by chromatography on silica gel [ELUTION WITH DICHLOROMETHANE: ETHYL ACETATE (60: 1) ] TO GIVE: 1. 5-BROMO-2-(1-METHYL-LH-TETRAZOL-5-YL) pyridine (1.397 g), a colorless solid, (TLC: silica-gel, hexanes: ethyl acetate (4: 1), Rf: 0. 3), 1H-NMR (DMSO-D6) (300 MHZ) 8 : 4.38 (s, 3H); 8.17 (d, 1H); 8.35 (dd, 1H); 8.96 (d, 1H). 2. 5-BROMO-2- (2-METHYL-2H-TETRAZOL-5-YL) pyridine (1.07 g), a colorless solid, (TLC: silica-gel, hexanes: ethyl acetate (4: 1), Rf: 0. 1). LH-NMR (DMSO-D) (300 MHZ) 8 4.46 (s, 3H); 8.09 (d, 1H) ; 8.28 (dd, 1H); 8.88 (d, 1H). Structure assignment based on HMBC experiments, in which long range coupling of the protons of CH3 to the C5 of the tetrazole ring is observed in the 1-METHYL-LH-ISOMER of Rf 0.3, but not in the 2-methyl-2H-isomer of Rf 0.1). The compound referred to as 5-bromo-2- (1-METHYL-1H-TETRAZOL-5-YL) PYRIDINE is thus the isomer of Rf 0.3 and the compound referred to as 5-BROMO-2-(2-METHYL-2H-TETRAZOL-5-YL) PYRIDINE is thus the isomer OF RF 0. 1
A mixture of 6.5 g unpurified 5-bromo-2-tetrazol-5-ylpyridine [Dong A Pharmaceuticals (WO 01/94342)] (-28 mmol) and sodium hydroxide (9 g, 125 mmol) in dry DMF was evaporated to dryness under reduced pressure. A stirred solution of the involatile residue in dry DMF (50 ML) was treated dropwise at ice-bath temperature with iodomethane (3.0 mL, 48 mmol). The stirred reaction mixture was allowed to warm and then maintained at room temperature for 2 hours. The reaction mixture was partitioned between iced water and ethyl acetate. The organic phase was washed with water, dried over magnesium sulfate, and tehn evaporated under reduced pressure to give a residue that was purified by chromatography on silica gel [elution with dichloromethane: ethyl acetate (60: 1) ] to give: 1. 5-BROMO-2- (L-METHYL-LH-TETRAZOL-5-YL) pyridine (1.397 g), a colorless solid, (TLC: silica-gel, hexanes: ethyl acetate (4: 1), Rf: 0. 3), (DMSO-D6) (300 MHZ) 8 : 4.38 (s, 3H); 8.17 (d, 1H) ; 8.35 (dd, 1H); 8.96 (d, 1H). 2. 5-BROMO-2- (2-METHYL-2H-TETRAZOL-5-YL) pyridine (1.07 g), a colorless solid, (TLC: silica-gel, hexanes: ethyl acetate (4: 1), Rf: 0. 1). 1H-NMR (DMSO-D6) (300 MHZ) 8 4.46 (s, 3H); 8.09 (d, 1H); 8.28 (dd, 1H); 8.88 (d, 1H). Structure assignment based on HMBC experiments, in which long range coupling of the protons of CH3 to the C5 of the tetrazole ring is observed in the 1-METHYL-LH-ISOMER of Rf 0.3, but not in the 2-methyl-2H-isomer of Rf 0.1). The compound referred to as 5-bromo-2- (1-METHYL-LH-TETRAZOL-5-YL) pyridine is thus the isomer of Rf 0.3 and the compound referred to as 5-BROMO-2- (2-METHYL-2H-TETRAZOL-5-YL) pyridine is thus the isomer OF RF 0. 1
With potassium hydroxide; In N,N-dimethyl-formamide; at 20℃; for 23h; To the solution of crude <strong>[380380-60-9]5-bromo-2-(2H-tetrazol-5-yl)pyridine</strong>(3.15 g,.13.9 mmol) in DMF (32 mL) was added MeI (7.92 g, 55.8 mmol) and KOH (1.95 g, 34.8 mmol) at room temperature. The mixture was stirred for 23 h at r.t.. The reaction mixture was poured into ice water (100 mL) and extracted with EtOAc. The organic layer was washed with brine, dried (Na2SO4), and evaporated under vacuum to give a residue, further purified by flash column chromatography (hexanes - EtOAc from 50: 1 to 10:1) to give 5-bromo-2- (2-methyl-2H-tetrazol-5-yl)pyridine as yellow solid (1.32 g, 43% yield over 2 steps) and 5- bromo-2-(l-methyl-lH-tetrazol-5-yl)pyridine as a white solid (0.97 g, 32% yield, 2 steps).

  • 2
  • [ 97483-77-7 ]
  • [ 380380-60-9 ]
YieldReaction ConditionsOperation in experiment
91.8% With pyridine; sodium azide; zinc(II) chloride; at 40 - 120℃; for 2h; Pyridine (40.0 mL, 4.0 v/w) was placed in a reactor, and zinc chloride (11.2 g, 81.9 mmol) was added dropwise at 40C or less. Thereafter, sodium azide (8.90 g, 137 mmol) and 5-bromo-2-cyanopyridine (10.0 g, 54.6 mmol) were added into the reactor, and the reaction mixture was stirred to reflux at 120C for 2 hr. After the termination of the reaction, the reaction product was cooled to room temperature, added with purified water (200 mL, 20.0 v/w), stirred at room temperature for 1 hr, filtered, and washed with purified water (200 mL, 20.0 v/w). The filtered solid was added with a 6 N hydrochloric acid aqueous solution (200 mL, 20.0 v/w) and then stirred at room tem[43jperature for 2 hr. The reaction product was filtered, washed with purified water (200mL, 20.0 v/w), and concentrated under reduced pressure, thus yielding a desired whitecompound. Yield (11.34 g, 91.8%), Purity 99.4%5-bromo-2-(2H-tetrazol-5-yl)pyridine:1H NMRoe (DMSO-d6, ppm) 8.95 (d,1H), 8.35 (dd,1H), 8.17 (d,1H)
With sodium azide; ammonium chloride; In DMF (N,N-dimethyl-formamide); at 120℃; for 1h; 5-Bromo-2-tetrazol-5-ylpyridine. A mixture OF 3-bromo-6-cyano-pyridine (2 g, 10.9 mmol), sodium azide (0.85 g, 13 mmol), and ammonium chloride (0.59 g, 11 mmol) in N,N-dimethylformamide (20 mL) was heated for 1 h at 120 C. The reaction mixture was diluted with ethyl acetate (~ 100 mL) and the product was isolated by filtration and then washed with ethyl acetate to give the title compound, an off-white amorphous solid which was used in the next step without further purification.
With sodium azide; ammonium chloride; In DMF (N,N-dimethyl-formamide); at 120℃; for 1h; 5-BROMO-2-TETRAZOL-5-YLPYRIDINE A mixture of 3-BROMO-6-CYANO-PYRIDINE (2 g, 10.9 mmol), sodium azide (0.85 g, 13 mmol), and ammonium chloride (0. 59 g, 11 mmol) in N, N-DIMETHYLFORMAMIDE (20 mL) was heated for 1 h at 120 C. The reaction mixture was diluted with ethyl acetate (-100 ML) and the product was isolated by filtration and then washed with ethyl acetate to give the title compound, an off-white amorphous solid which was used in the next step without further purification.
With sodium azide; ammonium chloride; In DMF (N,N-dimethyl-formamide); at 120℃; for 1h; 5-Bromo-2-tetrazol-5-ylpyridine A mixture of 3-BROMO-6-CYANO-PYRIDINE (2 g, 10.9 mmol), sodium azide (0.85 g, 13 mmol), and ammonium chloride (0.59 g, 11 mmol) in N, N-dimethylformamide (20 mL) was heated for 1 h at 120 C. The reaction mixture was diluted with ethyl acetate (-100 mL) and the product was isolated by filtration and then washed with ethyl acetate to give the title compound, an off-white amorphous solid which was used in the next step without further purification
With sodium azide; ammonium chloride; In DMF (N,N-dimethyl-formamide); at 120℃; for 1h; A mixture of 3-bromo-6-cyano-pyridine (2 g, 10.9 mmol), sodium azide (0.85 g, 13 mmol), and ammonium chloride (0.59 g, 11 mmol) in N, N-DIMETHYLFORMAMIDE (20 mL) was heated for 1 h at 120 C. The reaction mixture was diluted with ethyl acetate (-100 mL) and the product was isolated by filtration and then washed with ethyl acetate to give the title compound, an off-white amorphous solid which was used in the next step without further purification.
To the solution of 5-bromopicolinonitrile (2.33 g, 12.7 mmol) in DMF (26 mL) was added NH4Cl (2.18 g, 40.7 mmol) and NaN3 (1.24 g, 19.1 mmol) at r.t.and the mixture was heated to 120 0C for 4 h. The reaction mixture was poured into ice water (100 mL) and acidified to pH=2 with 6N HCl, stirred for 1 h, and the mixture was extracted with EtOAc. The organic phases were combined, dried (Na2SO4) and evaporated under vacuum to give crude 5-bromo-2-(2H-tetrazol-5-yl)pyridine in 3.15g, which was used for next step without further purification.

  • 3
  • [ 380380-60-9 ]
  • [ 85951-09-3 ]
  • [ 700370-50-9 ]
  • C21H38BrN5O2Si2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 0 - 20℃; 2-[5-(5-bromopyridin-2-yl)-1H-tetrazol-1-ylpropane-1,3-diol. 5-Bromo-2-(2H-tetrazol-5-yl)pyridiue 0.56 g (2.5 mmol) (WO 0194342 Al, the free acid was generated by dissolving the material obtained following the procedure in WO 0194342 Al (1 g) in hot water (70 mL, 90 C) ; upon addition OF HCl (aqueous, 1M, 4 mL) and cooling to room temperature the free acid precipitated, was collected by filtration, washed with water and dried under high vacuum to give 0.56 g free acid), triphenylphosphine (0.65 g, 2.5 mmol) and 1,3-bis-(tert-butyl-dimethyl-silanyloxy)-propan-2-ol (0.79 g, 2.5 mmol) (D. P. Curran and J.-C. Chao, Synth. Commun. 20, No 22, 1990, 3575-3584) were dissolved/suspended in dry THF (25 mL). It was cooled to 0C and diisopropylazodicarboxylate (0.49 mL, 2.5 mmol) was added and the reaction was allowed to warm to room temp. over night. The solvent was evaporated under reduced pressure and the residue subjected to chromatography on silica gel with hexanes/ethyl acetate (30: 1) to give the bis-silyl ether of the title compound as a mixture together with the corresponding 2H-tetrazole regioisomer (809 mg). This mixture was dissolved in dry THF (10 mL), cooled to 0C and tetrabutylammonium fluoride (1M in THF, 5 mL, 5 mmol) was added drop wise. After one hour solvent was evaporated and the residue subjected to chromatography on silica gel with dichloromethane/acetone (3:1 to 2:1) to give 318 mg of the title compound and 69 mg of the corresponding regioisomeric 2H-substituted tetrazole. The assignment of structure was based on NOE-NMR experiments with the title compound. 1H-NMR (DMSO-d6) delta: 3.80-3.95 (m, 4H); 5.01 (t, 2H); 5.69 (m, 1H) ; 8.14 (m, 1H); 8.35 (m, 1H) ; 8.94 (m, 1H).
  • 4
  • [ 380380-60-9 ]
  • [ 590-17-0 ]
  • [ 1217273-69-2 ]
YieldReaction ConditionsOperation in experiment
52% With potassium hydroxide; In N,N-dimethyl-formamide; at 0 - 20℃; KOH (1.7 g, 30.6 mmol) was added to a solution of Intermediate 37 (3.46 g, 15.3 mmol) in 35 mL of DMF at 0 C. Then BrCH2CN (3.2 mL, 45.9 mmol) was added dropwise. The mixture was stirred at r.t. o.n. Then 400 mL of ice-water was added and extracted with EtOAc. The organic phase was washed with brine, dried and evaporated. Purification by silica gel column (petroleum ether/EtOAc=1/3) gave 2.1 g of Intermediate 38 (yield 52%).
  • 5
  • [ 380380-60-9 ]
  • [ 380380-59-6 ]
YieldReaction ConditionsOperation in experiment
75% Intermediate 37 (5.3 g, 23.4 mol) was dissolved in Ac2O (80 mL) at r.t. and pyridine (9.2 mL) was added. The mixture was heated to 130 C. for 1.5 h. Then the solution was poured into ice-water (400 mL) and PH was adjusted to 3-4 with 6 N HCl (aq). The mixture was stirred for 20 min and filtered. The desired product was collected as a white solid (4.25 g, 75%).
  • 7
  • [ 380380-60-9 ]
  • (5S)-3-[3-fluoro-4-[6-(2-methyltetrazol-5-yl)pyridin-3-yl]phenyl]-5-(hydroxymethyl)-1,3-oxazolidin-2-one [ No CAS ]
  • 8
  • [ 380380-60-9 ]
  • C19H17FN6O4 [ No CAS ]
  • 9
  • C6H7BrN4 [ No CAS ]
  • [ 380380-60-9 ]
YieldReaction ConditionsOperation in experiment
89% With hydrogenchloride; sodium nitrite; In water; at -5 - 10℃; for 0.5h; Using the two compounds (III) obtained in Examples 7-13 as reactants, under different reaction conditions,Sodium nitrite in acid(IV) under the conditions of the reaction.The compound of formula (III)Add dilute hydrochloric acid,Then adding sodium nitrite in portions,Control the reaction solution temperature, plus complete,The reaction was continued for 30 min,temperature control,Extracted with dichloromethane (2 x 20 ml)The combined dichloromethane phase was concentrated,Then, 20 ml of isopropyl acetate was added,? 50 stirring 1h,The filter cake was washed three times with 10 ml of isopropyl acetate and dried at 35 CDried to give the product. Wherein the methyl isomer by-product N1 is not detected.
  • 10
  • [ 380380-60-9 ]
  • [ 50-00-0 ]
  • [ 380380-64-3 ]
YieldReaction ConditionsOperation in experiment
90.4% With palladium 10% on activated carbon; hydrogen; In methanol; at 20℃; under 1500.15 Torr; for 3h; 1.5 L of methanol,5-bromo-2- (2H-tetrazol-5-yl) pyridine (226 g)Formaldehyde (90g),10% palladium on carbon (20 g) was added to the reactor,Under a hydrogen atmosphere (0.2 MPa)Stirred at room temperature for 3 hours, the reaction was completed,Organic phase evaporated,Recrystallization from acetonitrile,To give the product 2-methyl-5- (5-bromo-2-yl) tetrazolium,217 g, yield: 90.4%.
  • 11
  • [ 380380-60-9 ]
  • [ 74-88-4 ]
  • [ 380380-64-3 ]
YieldReaction ConditionsOperation in experiment
70.5% With calcium hydroxide; In dichloromethane; N,N-dimethyl-formamide; at 0 - 40℃; for 24h; The <strong>[380380-60-9]5-bromo-2-(2H-tetrazol-5-yl)pyridine</strong> (20.0 g, 88.4 mmol) prepared in Example 1 was added with 20.0 mL of N,N-dimethyl formamide and 180.0 mL of methylene chloride and then further added with calcium hydroxide (3.94 g, 53.0 mmol), after which iodomethane (33.0 mL, 530.4 mmol) was slowly added dropwise thereto at 0C. Thereafter, the reaction solution was warmed to 40C and stuffed for 24 hr. After the termination of the reaction, the reaction solution was added with water, thus extracting an organic layer. The extracted organic layer was washed with saline and further extracted. The resulting organic layer was added with 300.0 mL of a 6 N hydrochloric acid aqueous solution to thus extract an aqueous layer, after which the separated organic layer was added with 60.0 mL of a 6 N hydrochloric acid aqueous solution, so that the aqueous layer was further extracted. Extraction was performed using HPLC until the amount of Ni was less than 5%. The separated aqueous layer was collected, and the pH thereof was adjusted to 10.6 at 40C or less using a 50% sodium hydroxide aqueous solution. The produced solid was filtered, washed with water, and concentrated under reduced pressure, thus obtaining a desired compound. Yield (16.2 g, 70.5%), N2/N] ratio % (98/2)
  • 12
  • [ 380380-60-9 ]
  • [ 1056039-85-0 ]
  • 13
  • [ 380380-60-9 ]
  • [ 1056035-09-6 ]
  • 14
  • [ 380380-60-9 ]
  • [ 1056035-10-9 ]
  • 15
  • [ 380380-60-9 ]
  • [ 18107-18-1 ]
  • [ 380380-64-3 ]
YieldReaction ConditionsOperation in experiment
28.5% In tetrahydrofuran; hexane; at 0 - 20℃; for 3h; To a stirred mixture of 5-bromo-2-(2//-tctrazol-5-yl)pyridinc (452 mg, 2 mmol) in THF (5 mL) was added (diazomethyl)trimethylsilane in hexane (2M, 5 mL, 10 mmol) at 0 C. The reaction mixture was stirred at room temperature for 3 h. TLC showed the reaction completed. The reaction mixture was quenched with water (30 mL) and extracted with ethyl acetate (10 mL><3). The combined organic layers were washed with water and brine, dried over sodium sulfate and concentrated in vacuo. The crude product was purified by column chromatography to afford the title compound as white solid (l80mg,28.5 % yield). NMR (500 MHz, DMSO-r/d) S: 9.00 - 8.89 (m, 1H), 8.32 (dd, J= 8.5, 2.4 Hz, 1H), 8.14 (d, J= 8.4 Hz, 1H), 4.34 (s, 3H).
  • 16
  • [ 380380-60-9 ]
  • tert-butyl 2-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)ethylcarbamate [ No CAS ]
  • 17
  • [ 380380-60-9 ]
  • 2-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)ethanamine [ No CAS ]
 

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