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Chemical Structure| 886372-63-0

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Product Details of [ 886372-63-0 ]

CAS No. :886372-63-0
Formula : C6H7FN2O
M.W : 142.13
SMILES Code : COC1=C(F)C=C(N)C=N1
MDL No. :MFCD07374960
InChI Key :CVMLVBYTEYUXOJ-UHFFFAOYSA-N
Pubchem ID :45480351

Safety of [ 886372-63-0 ]

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

Computational Chemistry of [ 886372-63-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.17
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 35.09
TPSA ?

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

48.14 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.48
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

0.58
Log Po/w (WLOGP)?

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

1.24
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.

0.37
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

1.06
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.94

Water Solubility

Log S (ESOL):?

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

-1.46
Solubility 4.88 mg/ml ; 0.0343 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.

-1.16
Solubility 9.74 mg/ml ; 0.0685 mol/l
Class?

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

Very soluble
Log S (SILICOS-IT)?

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

-2.05
Solubility 1.28 mg/ml ; 0.00897 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.

-6.76 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

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)

1.85

Application In Synthesis of [ 886372-63-0 ]

* 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 [ 886372-63-0 ]

[ 886372-63-0 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 886372-63-0 ]
  • [ 1253574-41-2 ]
  • [ 1253574-39-8 ]
YieldReaction ConditionsOperation in experiment
STEP 3: 4-(5-FLUORO^-(S-FLUORO-O-METHOXYPYRIDrN-S-YLAMrNO)PYRIDrN-S- YL)-6-METHYL- 1, 3, 5-TRIAZIN-2 -AMINE[00528] A solution of 4-(2-chloro-5-fluoropyridin-3-yl)-6-methyl-l,3,5-triazin-2-amine (100 mg, 0.417 mmol) and <strong>[886372-63-0]5-fluoro-6-methoxypyridin-3-amine</strong> (120 mg, 0.844 mmol) (Anichem, NJ, USA) in THF (2.0 mL) was cooled in an ice bath under nitrogen. A THF solution of LiHMDS (1 M in THF, 2500 muL, 2.500 mmol) was added dropwise. After 5 min, the cooling bath was removed. After a total of 22 min, HCl (5 N, 0.5 mL) was added. After 5 min, EtOAc (10 mL) and saturated NH4Cl (10 mL) were added. The organic layer was washed with water (2 x 5 mL). The combined aqueous layers were extracted with EtOAc (2 x 5 mL). The combined organic layers were dried over Na2SO4 and concentrated. The resulting residue was suspended in MeOH (5 mL) and filtered. The solid was washed with MeOH (2 x 2 mL), DCM (3 x 3 mL) and EtOAc (3 x 3 mL) to give the first batch of product as a brown solid. The combined washings were concentrated and purified on silica using 0-3% MeOH in DCM. The dark blue fraction contained the desired product (m/z 346) as a second batch. The combined product batches was suspended in ether (4 mL) and filtered to give the final product as a green solid (60 mg). LCMS (ES, pos.): calcd for Ci5H13F2N7O: 345.1; found: 346.2 (M+H)+. 1H NMR (400 MHz, d6-DMSO) delta 11.78 (s, 1 H); 8.56 (dd, J=9.78, 2.93 Hz, 1 H); 8.38 (br. s., 2 H); 8.28 (dd, J=12.81, 1.86 Hz, 1 H); 7.97 (br. s., 1 H); 7.84 (br. s., 1 H); 3.93 (s, 3 H); 2.44 (s, 3 H). 19F NMR (377 MHz, d6-DMSO) delta -140.84 (s, 1 F); -139.70 (s, 1 F).
  • 2
  • [ 886372-63-0 ]
  • [ 1253574-48-9 ]
  • [ 1253574-46-7 ]
YieldReaction ConditionsOperation in experiment
STEP 3 : 4-(5-CHLORO-2-(5-FLUORO-6-METHOXYPYRIDIN-3 -YLAMINO)PYRIDIN-3 - YL)-N-(2-METHOXYETHYL)-6-METHYL- 1 ,3,5-TRIAZIN-2 -AMINE[00535] A mixture of <strong>[886372-63-0]5-fluoro-6-methoxypyridin-3-amine</strong> (Anichem, NJ, USA, 100 mg, 0.704 mmol) and 4-(5-chloro-2-fluoropyridin-3-yl)-N-(2-methoxyethyl)-6-methyl-l,3,5-triazin- 2-amine (130 mg, 0.437 mmol) in THF (5 mL) was cooled in an ice bath and LiHMDS (1.0 M, 1500 muL, 1.500 mmol) was added under nitrogen. After 5 min, the cooling bath was removed. After 10 min, the mixture was neutralized with HCl (5 N, 0.3 mL) and then partitioned between EtOAc (20 mL) and water (10 mL). The organic layer was washed with water (5 mL). The combined aqueous layers were extracted with EtOAc (2 x 5 mL). The combined organic layers were dried over Na2SO4 and concentrated. The resulting solid was triturated with EtOAc (5 mL) and filtered. The yellow solid was rinsed with ether (2 x 3 mL) to give the desired product as a yellow powder (115 mg). LCMS (ES, pos.): calcd for Ci8Hi9ClFN7O2: 419.1; found: 420.2 (M+H)+. 1H NMR (400 MHz, d6-DMSO) mixture of rotamers delta 11.89, 11.67 (s, 1 H); 8.73 (dd, J=6.75, 2.64 Hz, 1 H); 8.14 - 8.58 (m, 4 H); 3.94 (2s, 3 H); 3.46 - 3.65 (m, 4 H); 3.23, 3.29 (s, 3 H); 2.46, 2.47 (s, 3 H). 19F NMR (377 MHz, d6-DMSO) delta -139.65 (s); 139.26 (s).
  • 3
  • [ 886372-63-0 ]
  • [ 1253569-32-2 ]
  • [ 1253575-42-6 ]
YieldReaction ConditionsOperation in experiment
With lithium hexamethyldisilazane; In tetrahydrofuran; at 0℃; EXAMPLE 246. 4-(2-(5-FLUORO-O-METHOXYPYRIDIN-S-YLAMINO)PYRIDIN-S-YL)- 6-METHYL-l,3,5-TRIAZIN-2-AMINESTEP 1 : 4-(2-(5-FLUORO-O-METHOXYPYRIDIN-S-YLAMINO)PYRIDIN-S-YL)-N1N- BIS(4-METHOXYBENZYL)-6-METHYL-l,3,5-TRIAZIN-2-AMINE[00637] A solution of THF (3 mL) containing <strong>[886372-63-0]5-fluoro-6-methoxypyridin-3-amine</strong> (87 mg, 0.613 mmol) (Anichem) and 4-(2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6- methyl-l,3,5-triazin-2-amine (Example 52; 182 mg, 0.409 mmol) was cooled to 0 0C in an ice bath and treated dropwise with 1 M LiHMDS (1.226 mL, 1.226 mmol). The solution was stirred at this temperature for 1.5 h and quenched with a saturated solution OfNH4Cl. The product was extracted with EtOAc (15 mL), dried over MgSO4, filtered and concentrated to give crude 4-(2-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)-N,N-bis(4- methoxybenzyl)-6-methyl-l,3,5-triazin-2-amine (269.7 mg, 0.475 mmol) as a bright yellow amorphous solid which was used in the next step without further purification, m/z (ESI, +ve ion) 568.0 (M+H)+. 1H NMR (400 MHz, CDCl3) delta 11.94 (1 H, s); 8.82 (1 H, dd, J=7.8, 2.0 Hz); 8.29 (1 H, dd, J=4.8, 2.1 Hz); 8.05 (1 H, dd, J=12.3, 2.2 Hz); 7.97 (1 H, d, J=2.3 Hz); 7.20 (4 H, dd, J=10.6, 8.6 Hz); 6.86 (4 H, t, J=9.0 Hz); 6.78 (1 H, dd, J=7.8, 4.7 Hz); 4.84 (2 H, br. s.); 4.83 (2 H, br. s.); 4.01 (3 H, s); 3.81 (3 H, s); 3.79 (3 H, s); 2.58 (3 H, s).
With lithium hexamethyldisilazane; In tetrahydrofuran; at 0℃; for 1.75h; LiHMDS (1M in THF, 0.694 mL, 0.694 mmol) was added (dropwise) to a solution of <strong>[886372-63-0]5-fluoro-6-methoxypyridin-3-amine</strong> (27, 49.3 mg, 0.347mmol; Anichem, Inc.,North Brunswick, NJ) and4-(2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine2(2a; 103 mg, 0.231 mmol) in THF (3 mL) at 0 C, and the resulting mixture was stirred at 0 C for 105 min. The reaction mixture was then quenched (at 0 C) with saturated aqueous NH4Cl solution and extracted with EtOAc (15 mL). The organic extract was dried over MgSO4, filtered, and concentrated in vacuo to provide 4-(2-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (146 mg, 0.257 mmol, >99% yield) as a bright-yellow solid, which was used without further purification.
  • 5
  • [ 886372-63-0 ]
  • [ 1253577-33-1 ]
  • [ 1253577-57-9 ]
  • 6
  • [ 886372-63-0 ]
  • [ 1253577-38-6 ]
  • [ 1253577-39-7 ]
  • 7
  • [ 886372-63-0 ]
  • [ 1253578-42-5 ]
  • [ 1253578-43-6 ]
  • [ 1253578-44-7 ]
  • 8
  • [ 886372-63-0 ]
  • [ 1379860-81-7 ]
  • [ 1253569-15-1 ]
  • 9
  • [ 886372-63-0 ]
  • C37H42FN9O3 [ No CAS ]
  • 16
  • [ 886372-63-0 ]
  • [ 1253571-14-0 ]
  • 21
  • [ 886372-63-0 ]
  • [ 1396085-99-6 ]
  • 22
  • [ 886372-63-0 ]
  • [ 1253575-91-5 ]
  • 23
  • [ 886372-63-0 ]
  • [ 1253575-88-0 ]
  • 24
  • [ 886372-63-0 ]
  • [ 1253575-93-7 ]
  • 28
  • [ 886372-63-0 ]
  • [ 1396087-06-1 ]
  • 29
  • [ 886372-63-0 ]
  • [ 1396087-13-0 ]
  • 30
  • [ 886372-63-0 ]
  • [ 1396087-19-6 ]
  • 31
  • [ 886372-63-0 ]
  • [ 1396087-78-7 ]
  • 32
  • [ 886372-63-0 ]
  • [ 1253576-28-1 ]
  • 33
  • [ 886372-63-0 ]
  • [ 1253571-12-8 ]
  • C34H34FN7O5 [ No CAS ]
  • 34
  • [ 953780-42-2 ]
  • [ 886372-63-0 ]
  • 35
  • tert-butyl (5-fluoro-6-methoxypyridin-3-yl)carbamate [ No CAS ]
  • [ 886372-63-0 ]
YieldReaction ConditionsOperation in experiment
49% With trifluoroacetic acid; at 20℃; for 2h; [00677] Intermediate 73: 5-fluoro-6-methoxy-pyridin-3-amine[00678] tert-Butyl N-(5-fluoro-6-methoxy-3-pyridyl)carbamate (315mg, 1 .3Ommol) was stirred in trifluoroacetic acid (1 .99mL, 26.01 mmol) for 2 hours. The reaction mixture was reduced in vacuo and the residue taken up in water (100 mL) and 1 M HCI (100 mL) and extracted with EtOAc (5OmL). To the aqueous layer was added solid sodium carbonate until a neutral/slightly basic pH was obtained. The aqueous was then further extracted with EtOAc (3 x 5OmL), organic fractionscollected, passed through phase separating filter paper and solvent reduced in vacuo to give 5-fluoro-6-methoxy-pyridin-3-amine (91mg, 0.64mmol, 49% yield) as a dark red oil.1H NMR (CDCI3,400MHZ) O/ppm: 7.45 (1H, d, J= 2.5Hz), 6.85 (1H, dd, J= 11.3Hz, 2.5Hz), 3.97(3H, 5).MS Method 2: RT: 0.91 mm, 143.0 m/z [M+H]
19 mg 2nd Step TFA (2 ml) was added to tert-butyl (5-fluoro-6-methoxypyridin-3-yl)carbamate (279 mg) obtained in the 1st step, followed by stirring at room temperature for 1 hour. The solvent was distilled away under reduced pressure and a 5M sodium hydroxide aqueous solution was added to the obtained residue at 0 C. so as to alkalify the mixture, followed by extraction with ethyl acetate. The organic layers were washed with saturated saline and dried over anhydrous sodium sulfate and the solvent was distilled away under reduced pressure. A light brown solid of 5-fluoro-6-methoxypyridin-3-amine (19 mg) was thus obtained. MS (ESI m/z): 143 (M+H)
 

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