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Chemical Structure| 7170-01-6

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Product Details of [ 7170-01-6 ]

CAS No. :7170-01-6
Formula : C3H5N3
M.W : 83.09
SMILES Code : CC1=NNC=N1
MDL No. :MFCD00233931
InChI Key :PZKFSRWSQOQYNR-UHFFFAOYSA-N
Pubchem ID :305560

Safety of [ 7170-01-6 ]

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

Computational Chemistry of [ 7170-01-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 6
Num. arom. heavy atoms 5
Fraction Csp3 0.33
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 21.35
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.

0.32
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

-0.55
Log Po/w (WLOGP)?

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

0.11
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.

-0.58
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

1.23
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.11

Water Solubility

Log S (ESOL):?

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

-0.63
Solubility 19.7 mg/ml ; 0.237 mol/l
Class?

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

Very soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

0.15
Solubility 116.0 mg/ml ; 1.4 mol/l
Class?

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

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

-1.14
Solubility 6.06 mg/ml ; 0.0729 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.

-7.2 cm/s

Druglikeness

Lipinski?

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

0.0
Ghose?

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

None
Veber?

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

0.0
Egan?

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

0.0
Muegge?

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

2.0
Bioavailability Score?

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

0.55

Medicinal Chemistry

PAINS?

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

0.0 alert
Brenk?

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

0.0 alert: heavy_metal
Leadlikeness?

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

No; 1 violation:MW<1.0
Synthetic accessibility?

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

1.29

Application In Synthesis of [ 7170-01-6 ]

* 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 [ 7170-01-6 ]

[ 7170-01-6 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 454-16-0 ]
  • [ 7170-01-6 ]
  • [ 1185019-82-2 ]
  • [ 1232038-78-6 ]
YieldReaction ConditionsOperation in experiment
49%; 13% With potassium carbonate; In dimethyl sulfoxide; at 120℃; for 1h; A mixture of l-fluoro-2-methoxy-4-nitrobenzene (821.414 mg, 4.8 mmol), 5-methyl- lH-l,2,4-triazole (800 mg, 9.63 mmol), K2CO3 (4.8 mmol) and DMSO (8 ml) was stirred at 120 0C for 1 h. After cooling to r.t., the r.m. was poured into ice H2O. The solid was filtered off, washed with H2O and dried in vacuo at 50 0C. Yield: 0.554 g of intermediate 9 (49 percent). The aq. layer was sat. with NaCl, extracted with DCM and the organic layer was dried (MgSO4), filtered and the solvent was evaporated in vacuo. The residue was purified by column chromatography over silicagel (eluent: DCM). The desired fraction was collected and the solvent was evaporated in vacuo. Yield: 0.147 g of intermediate 10 (13 percent).
49%; 13% With potassium carbonate; In dimethyl sulfoxide; at 120℃; for 1h; a) Preparation of intermediate 3 and intermediate 4 (regioisomers) A mixture of l-fluoro-2-methoxy-4-nitrobenzene (821 mg, 4.8 mmol), 5 -methyl- IH- 1,2,4-triazole (800 mg, 9.63 mmol), K2CO3 (4.8 mmol) and DMSO (8 ml) was stirred at 120 0C for 1 h. After cooling, the r.m. was poured into ice water. The solid was filtered off, washed with water and dried in vacuo at 50 0C. Yield: 0.554 g of intermediate 3 (49 percent). The aq. layer was saturated with NaCl, extracted with DCM and the organic layer was dried (MgSO4), filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: DCM). The desired fraction was collected and the solvent was evaporated. Yield: 0.147 g of intermediate 4 (13 percent).
49%; 13% With potassium carbonate; In dimethyl sulfoxide; at 120℃; for 1h; Example A2 a) Preparation of intermediate 3 and intermediate 4A mixture of l-fluoro-2-methoxy-4-nitrobenzene (821 mg, 4.8 mmol), 5-methyl-lH- 1,2,4-triazole (800 mg, 9.63 mmol), K2CO3 (4.8 mmol) and DMSO (8 ml) was stirred at 120 0C for 1 h. After cooling, the r.m. was poured into ice water. The solid was filtered off, washed with H2O and dried (in vacuo; 50 0C). Yield: 0.554 g of intermediate 3 (49 percent). The aq. layer was sat. with NaCl, extracted with DCM and the organic layer was dried (MgSO4), filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: DCM). The desired fraction was collected and the solvent was evaporated. Yield: 0.147 g of intermediate 4 (13 percent).
49%; 13% With potassium carbonate; In dimethyl sulfoxide; at 120℃; for 1h; A mixture of l-fluoro-2-methoxy-4-nitrobenzene (821 mg, 4.80 mmol), 5-methyl-lH- 1,2,4-triazole (800 mg, 9.63 mmol), K2C03 (4.80 mmol) and DMSO (8 ml) was stirred at 120 °C for 1 h. After cooling, the r.m. was poured into ice water. The solid was filtered off, washed with water and dried in vacuo at 50 °C. Yield: 0.55 g ofintermediate 37 (49 percent). The aq. layer was saturated with NaCl, extracted with DCM and the organic layer was dried (MgSC^), filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: DCM). The desired fraction was collected and the solvent was evaporated. Yield: 0.15 g ofintermediate 38 (13 percent).
49%; 13% With potassium carbonate; In dimethyl sulfoxide; at 120℃; for 1h; A mixture of l-fluoro-2-methoxy-4-nitrobenzene (821 mg, 4.80 mmol), 5-methyl-lH-1,2,4-triazole (800 mg, 9.63 mmol), K2C03 (4.80 mmol) and DMSO (8 ml) was stirred at 120 °C for 1 h. After cooling, the r.m. was poured into ice water. The solid was filtered off, washed with water and dried in vacuo at 50 °C. Yield: 0.55 g ofintermediate 37 (49 percent). The aq. layer was saturated with NaCl, extracted with DCM and the organic layer was dried (MgS04), filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: DCM). The desired fraction was collected and the solvent was evaporated. Yield: 0.15 g of intermediate 38 (13 percent).
49%; 13% With potassium carbonate; In dimethyl sulfoxide; at 120℃; for 1h; A mixture of <strong>[454-16-0]1-fluoro-2-methoxy-4-nitrobenzene</strong> (821 mg, 4.80 mmol), 5-methyl-1H-1,2,4-triazole (800 mg, 9.63 mmol), K2CO3 (4.80 mmol) and DMSO (8 ml) was stirred at 120° C. for 1 h. After cooling, the r.m. was poured into ice water. The solid was filtered off, washed with water and dried in vacuo at 50° C. Yield: 0.55 g of intermediate 37 (49percent). The aq. layer was saturated with NaCl, extracted with DCM and the organic layer was dried (MgSO4), filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: DCM). The desired fraction was collected and the solvent was evaporated. Yield: 0.15 g of intermediate 38 (13percent).

  • 2
  • [ 7170-01-6 ]
  • [ 454-16-0 ]
  • [ 1185019-82-2 ]
YieldReaction ConditionsOperation in experiment
37% With potassium carbonate; In N,N-dimethyl-formamide; at 85℃; Example 41 b. l-(2-methoxy-4-nitrophenyl)-3-methyl-lH-l,2,4-triazoleA mixture of 3-methyl-lH-[l,2,4]triazole (2.4 g, 29.21 mmol), l-fluoro-2-methoxy-4- nitrobenzene (5.0 g, 29.21 mmol) and potassium carbonate (8.06 g, 58.42 mmol) in DMF (50 mL) was heated overnight at 85°C in a pressure vessel. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was suspended in water and the mixture extracted with dichloromethane. The organic extracts were combined, washed with brine, dried over anhydrous Na2SO4, filtered and concentrated. The residue was dissolved in dichloromethane (50 mL) and hexane was added in small portions until the solution become slightly turbid. The turbid solution was left at room temperature. The precipitation was collected by filtration, washed with hexane to give 2.5 g of title compound (37 percent Yield).1U NMR (400 MHz, CHLOROFORM-J) delta ppm 2.51 (s, 3 H) 4.10 (s, 3 H) 7.90 - 8.06 (m, 2 H) 8.10 (d, I H) 8.87 (s, I H)
35% With potassium carbonate; In N,N-dimethyl-formamide; at 20 - 85℃; for 16h;Sealed tube; Inert atmosphere; To a stirred solution of <strong>[454-16-0]1-fluoro-2-methoxy-4-nitrobenzene</strong> (2.5 g, 14.60 mmol) in DMF (25 mL) under an argon atmosphere were added potassium carbonate (4 g, 29.20 mmol) and 3-methyl-1H-1, 2, 4-triazole (1.2 g, 14.60 mmol) at room temperature. The reaction mixture was stirred at 85 oC for 16 h in a sealed tube. After consumption of the starting material (monitored by TLC), the reaction mixture was diluted with water (100 mL) and extracted with EtOAc (2 x 50 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo. The crude material was purified by column chromatography using 15-25percent EtOAc:hexane to afford <strong>[454-16-0]1-fluoro-2-methoxy-4-nitrobenzene</strong> (1.2 g, 35percent) as an off-white solid. 1H-NMR (CDCl3, 400 MHz): delta 8.87 (s, 1H), 8.10 (d, 1H), 8.00-7.97 (m, 2H), 4.10 (s, 3H), 2.50 (s, 3H); LCMS: 234.9 (M+1); (column; Ascentis Express C-18 (50 × 3.0 mm, 2.7 mum); RT 2.02 min. 0.025percent Aq TFA+5percent ACN: ACN+5percent 0.025percent Aq TFA; 1.2 mL/min); TLC: 30percent EtOAc:hexane (Rf: 0.2).
35% With potassium carbonate; In N,N-dimethyl-formamide; at 85℃; for 16h;Inert atmosphere; Sealed tube; Synthesis of <strong>[454-16-0]1-fluoro-2-methoxy-4-nitrobenzene</strong> (1023) To a stirred solution of <strong>[454-16-0]1-fluoro-2-methoxy-4-nitrobenzene</strong> (2.5 g, 14.60 mmol) in DMF (25 mL) under an argon atmosphere were added potassium carbonate (4 g, 29.20 mmol) and 3-methyl-1H-1,2,4-triazole (1.2 g, 14.60 mmol) at room temperature. The reaction mixture was stirred at 85° C. for 16 h in a sealed tube. After consumption of the starting material (monitored by TLC), the reaction mixture was diluted with water (100 mL) and extracted with EtOAc (2×50 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo. The crude material was purified by column chromatography using 15-25percent EtOAc:hexane to afford <strong>[454-16-0]1-fluoro-2-methoxy-4-nitrobenzene</strong> (1.2 g, 35percent) as an off-white solid. 1H-NMR (CDCl3, 400 MHz): delta 8.87 (s, 1H), 8.10 (d, 1H), 8.00-7.97 (m, 2H), 4.10 (s, 3H), 2.50 (s, 3H); LCMS: 234.9 (M+1); (column; Ascentis Express C-18 (50×3.0 mm, 2.7 mum); RT 2.02 min. 0.025percent Aq TFA+5percent ACN: ACN+5percent 0.025percent Aq TFA; 1.2 mL/min); TLC: 30percent EtOAc:hexane (Rf: 0.2).
 

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