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Chemical Structure| 6967-12-0

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Product Details of [ 6967-12-0 ]

CAS No. :6967-12-0
Formula : C7H7N3
M.W : 133.15
SMILES Code : C1=N[NH]C2=C1C=CC(=C2)N
MDL No. :MFCD00005696
InChI Key :KEJFADGISRFLFO-UHFFFAOYSA-N
Pubchem ID :81423

Safety of [ 6967-12-0 ]

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

Computational Chemistry of [ 6967-12-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 9
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 2.0
Molar Refractivity 40.5
TPSA ?

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

54.7 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.49
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

1.55
Log Po/w (WLOGP)?

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

1.15
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.

0.51
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

1.36
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.01

Water Solubility

Log S (ESOL):?

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

-2.31
Solubility 0.655 mg/ml ; 0.00492 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.

-2.31
Solubility 0.655 mg/ml ; 0.00492 mol/l
Class?

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

Soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-2.52
Solubility 0.404 mg/ml ; 0.00303 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.

-6.01 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

1.0
Bioavailability Score?

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

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

1.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

1.35

Application In Synthesis of [ 6967-12-0 ]

* 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 [ 6967-12-0 ]

[ 6967-12-0 ] Synthesis Path-Downstream   1~8

  • 1
  • [ 6967-12-0 ]
  • [ 261953-36-0 ]
YieldReaction ConditionsOperation in experiment
80% A concentrated hydrochloric acid (35 mL, 420 mmol) and an aqueous solution (30 mL) of sodium nitrite (6.64g, 96 mmol) were added to a suspension prepared by adding water (30 mL) to 6-aminoindazole (10.4 g, 78 mmol) at0C and stirred at 0C for 30 minutes. Subsequently, to this solution, an aqueous solution (30 mL) of potassium iodide(15.91 g, 96 mmol) was added at 0C, stirred at room temperature for 30 minutes, to which dichloromethane (80 mL)was then added, and stirred at 40C for 2 hours. The reaction mixture was cooled down to 0C, then adjusted to pH =14 with a 3N sodium hydroxide aqueous solution, and the precipitate was taken by filtration. The resulting precipitatewas washed with 10% sodium thiosulfate, dissolved in tetrahydrofuran, and then silica gel was added. After stirring atroom temperature for 1 hour, hexane (600 mL) was added and filtered. The residue was washed twice with a THF/hexane(1/3 (v/v)) solution, then the solvent was distilled away under a reduced pressure to obtain the title compound (15.23 g,80%) as an orange powder.1H NMR (400 MHz, CDCl3) δ 10.24 (1H, br, s), 8.04 (1H, br s), 7.92 (1H, br s), 7.51 (1H, br d, J = 8.4 Hz), 7.46 (1H, dd,J = 8.4, 1.2 Hz).
48% With sodium hydroxide; concentrated aqueous HCl; Ki; sodium hydrogencarbonate; sodium nitrite; In tetrahydrofuran; hexane; water; (i) To 6-aminoindazole (40.8 g, 0.3065 mol, 1 equiv) in a 2-liter (2-L) round-bottom flask containing a large magnetic stir bar was added ice (256 g), followed by water (128 mL) and the reaction vessel was lowered into an ice bath. To this stirring slurry at 0 C. was added concentrated aqueous HCl (128 mL, 1.53 mol, 5 equiv). Immediately after, a solution of NaNO2 (23.3 g, 0.338 mol, 1.1 equiv) in water (96 mL) was added. After 10 min of stirring at 0 C., KI (61 g, 0.368 mol, 1.2 equiv) was added very slowly at first (~100 mg at a time because the first small bits of KI cause an abrupt evolution of gas) then more rapidly (5 min total time). The cold bath was removed and the reaction mixture was warmed to 40 C. (gas evolved). When the rate of gas evolution decreased (~30 min) the reaction mixture was warmed to 50 C. for 30 min. The mix was then cooled to 23 C., and 3N NaOH (320 mL) was added to neutralize followed by 50% saturated NaHCO3 (320 mL). The slurry was then filtered through a Buchner funnel to give a dark reddish-brown solid. The solid was taken up in warm THF (800 mL) and silica (600 mL dry) was added with stirring. To this slurry was added hexane (1.2 L) and the mix was vacuum filtered through a pad of silica (300 mL) in a large fritted filter. The silica was further washed with 2 L of 40% THF in hexane. The filtrates were combined and concentrated under reduced pressure to give a solid. The solid was further triturated with ethyl acetate (~100 mL), filtered and dried under reduced pressure to give 6-iodo-1H-indazole as a light brown solid (36.1 g, 48% yield): Rf sm 0.12, p 0.48 (Hex-EtOAc 1:1); 1H NMR (300 MHz, CDCl3) 7.9 (s, 1H), 7.8 (s, 1H), 7.42 (d, 1H), 7.33 (d, 1H); MS (ES) [m+H]/z Calc'd 245, Found 245, [m-H]/z Calc'd 243, Found 243.
Example 12 6-Iodo-1H-indazole (compound 20) sodium nitrite (5.87 g, 85 mmol) in water (20 ML) was added dropwise to an ice-cooled solution of 6-aminoindazole (10 g, 75.6 mmol) in DMF (80 ML) and hydrochloric acid (6M, 40 ML).. The mixture was stirred for 30 minutes.. potassium iodide (13.5 g) was then added in small portions (gas evolution occurred) and the mixture stirred for 1 h before warming to room temperature for 16 h.. The reaction was neutralized with aqueous sodium bisulfite, followed by aqueous sodium hydroxide.. The mixture was filtered to remove solids, and the solid was washed with water to remove impurities, and then with ethyl acetate and THF to collect the product.. The organic washes were evaporated and recombined with the aqueous layer for extraction with ethyl acetate (3*250 ML).. The organic layer was washed sequentially with water and brine, dried over sodium sulfate, and the solvent removed in vacuo.. Filtration chromatography on silica gel (35-60% ethyl acetate in hexane) gave a yellow solid which was triturated firstly with 50% ethyl acetate in hexane and then with ethyl acetate to yield the product (4.96 g).
0.9 g 6-Aminoindazole (1.0 g, 7.5 mmol) was mixed with ice (6 g) and water (3.5 mL). The reaction mixture was cooled to 0C and concentrated aqueous hydrochloride solution (3.8 mL) was added followed by a solution of sodium nitrite (0.6 g, 8.2 mmol) in water (2.5 mL). After 10 min of stirring at 0C potassium iodide (1.3 g, 9.0 mmol) was added in few portions. Then the cold bath was removed and reaction mixture was warmed to 40C, heated for 40 min and next the temperature was increased to 50C and heated for another 30 min. After cooled to ambient temperature the solution was alkalized with 10% NaOH. The brown precipitate was collected by filtration and washed with saturated aqueous solution of sodium hydrogen carbonate. The crude product was dissolved in tetrahydrofuran (25 mL) and refluxed with silica gel for 10 min. To this slurry hexane was added and the mixture was vaccum filtered through a silica pad. The silica was washed with solution of tetrahydrofuran in hexane (2:3). The filtrate was concentrated under reduced pressure to give 6-iodoindazole (0.9 g). The 6-iodoindazole (0.9 g, 3.9 mmol) was dissolved in dry dichloromethane (30 mL), cooled to 0C and N- bromosuccinimide (0.8 g, 4.3 mmol) was added in portions. The reaction mixture was stirred at 0C for lh. The precipitate was collected by filtration and washed with dichloromethane. The obtained product 3-bromo-6-iodo-lH-indazole was used to the next step without further purification. LC-MS (m/z) 324.8 (M+l).

  • 2
  • [ 1192711-88-8 ]
  • [ 6967-12-0 ]
  • [ 1192708-79-4 ]
YieldReaction ConditionsOperation in experiment
With chloro-trimethyl-silane; In butan-1-ol; at 115.0℃; for 8.0h; To a mixture of <strong>[1192711-88-8]2-chloro-7H-pyrrolo[2,3-d]pyrimidine-4-amine</strong> (0.06 g, 0.353 mmol) in nBuOeta (0.7 mL) was added 6-aminoindazole (0.094 g, 0.70 mmol) and TMSCl (0.023 mL, 0.175 mmol). After heating at 115 C for 8 h, it was cooled and purifed by prep etaPLC to give N2-(lH-indazol-6-yl)- 7H-pyrrolo [2,3-d]pyrimidin-2,4-diamine (0.012 g, MS calcd for C13H1 1N7 265.3, found 266.1; UV 216.9, 308.0 nm).
  • 3
  • [ 126712-07-0 ]
  • [ 6967-12-0 ]
  • [ 126-81-8 ]
  • 2-methoxy-12,12-dimethyl-12,13-dihydropyrazolo[4,5,1-de]quinolino[4,3,2-mn]acridin-14(11H)-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
79% With copper(l) iodide; caesium carbonate; In dimethyl sulfoxide; at 100℃; for 14h; General procedure: A 25-mL flask was charged with o-halogenated benzaldehyde 1 (1.0mmol), 1H-indazol-6-amine 2 (133 mg, 1.0 mmol), cyclohexane-1,3-dione 3 (1.0 mmol), CuI (10 mg, 0.05 mmol), Cs2CO3 (652 mg, 2.0mmol), and DMSO (10 mL). The mixture was stirred at reflux untilcompletion (TLC monitoring). The solid was filtered off, and the filtratewas distilled under reduced pressure to recover the solvent; theresidue was purified by chromatography (silica gel, EtOAc-petroleumether, 1:2) to give 4.
  • 4
  • [ 126712-07-0 ]
  • [ 6967-12-0 ]
  • [ 504-02-9 ]
  • 2-methoxy-12,13-dihydropyrazolo[4,5,1-de]quinolino[4,3,2-mn]acridin-14(11H)-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% With copper(l) iodide; caesium carbonate; In dimethyl sulfoxide; at 100℃; for 18h; General procedure: A 25-mL flask was charged with o-halogenated benzaldehyde 1 (1.0mmol), 1H-indazol-6-amine 2 (133 mg, 1.0 mmol), cyclohexane-1,3-dione 3 (1.0 mmol), CuI (10 mg, 0.05 mmol), Cs2CO3 (652 mg, 2.0mmol), and DMSO (10 mL). The mixture was stirred at reflux untilcompletion (TLC monitoring). The solid was filtered off, and the filtratewas distilled under reduced pressure to recover the solvent; theresidue was purified by chromatography (silica gel, EtOAc-petroleumether, 1:2) to give 4.
  • 5
  • [ 4341-24-6 ]
  • [ 126712-07-0 ]
  • [ 6967-12-0 ]
  • 2-methoxy-12-methyl-12,13-dihydropyrazolo[4,5,1-de]quinolino[4,3,2-mn]acridin-14(11H)-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
79% With copper(l) iodide; caesium carbonate; In dimethyl sulfoxide; at 100℃; for 12h; General procedure: A 25-mL flask was charged with o-halogenated benzaldehyde 1 (1.0mmol), 1H-indazol-6-amine 2 (133 mg, 1.0 mmol), cyclohexane-1,3-dione 3 (1.0 mmol), CuI (10 mg, 0.05 mmol), Cs2CO3 (652 mg, 2.0mmol), and DMSO (10 mL). The mixture was stirred at reflux untilcompletion (TLC monitoring). The solid was filtered off, and the filtratewas distilled under reduced pressure to recover the solvent; theresidue was purified by chromatography (silica gel, EtOAc-petroleumether, 1:2) to give 4.
  • 6
  • [ 60456-77-1 ]
  • [ 6967-12-0 ]
  • [ 614-16-4 ]
  • 9-(4-(furan-2-yl)phenyl)-7-phenyl-6,9-dihydro-1H-pyrazolo[3,4-f]quinoline-8-carbonitrile [ No CAS ]
  • 7
  • [ 6967-12-0 ]
  • [ 53554-29-3 ]
  • C14H13N5O3 [ No CAS ]
  • 8
  • [ 6967-12-0 ]
  • [ 70395-35-6 ]
  • 2-chloro-2-fluoro-N-(1H-indazol-6-yl)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
43% With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; N-ethyl-N,N-diisopropylamine; In dichloromethane; ethyl acetate; at 0 - 20℃; for 1.5h; General procedure: To a stirred solution of 5-amino-1-naphthol (126 mg, 0.792 mmol) and <strong>[70395-35-6]sodium chlorofluoroacetate</strong> (159 mg,1.18 mmol) in dichloromethane (8 mL) was added T3P (50 wt%solution in AcOEt, 701 μL, 1.18 mmol) and N,N-diisopropylethylamine(DIPEA) (273 μL, 1.57 mmol) at 0C. Afterstirred at ambient temperature for 1 h, the reaction mixturewas diluted with water and extracted thrice with CHCl3. Thecombined organic layers were washed with brine, dried overNa2SO4, filtered and concentrated in vacuo. The residue waspurified by flash column chromatography on silica gel (hexane/AcOEt = 3 : 1) to afford the title compound (37.2 mg, 18% yield) as a pale purple solid.
 

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Technical Information

Categories

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