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Chemical Structure| 31181-79-0 Chemical Structure| 31181-79-0

Structure of 31181-79-0

Chemical Structure| 31181-79-0

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Product Details of [ 31181-79-0 ]

CAS No. :31181-79-0
Formula : C6H6FNO
M.W : 127.12
SMILES Code : FC1=CC=CN=C1CO
MDL No. :MFCD09025826
InChI Key :FKTCIWBKNWUDAX-UHFFFAOYSA-N
Pubchem ID :19703803

Safety of [ 31181-79-0 ]

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

Computational Chemistry of [ 31181-79-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
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 30.32
TPSA ?

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

33.12 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.43
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

0.1
Log Po/w (WLOGP)?

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

0.98
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.

0.31
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

1.63
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.89

Water Solubility

Log S (ESOL):?

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

-1.12
Solubility 9.68 mg/ml ; 0.0761 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.

-0.35
Solubility 56.7 mg/ml ; 0.446 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

-2.09
Solubility 1.03 mg/ml ; 0.00807 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.

-7.0 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)

1.39

Application In Synthesis of [ 31181-79-0 ]

* 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 [ 31181-79-0 ]

[ 31181-79-0 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 31181-79-0 ]
  • [ 149489-32-7 ]
YieldReaction ConditionsOperation in experiment
80% With thionyl chloride; In dichloromethane; at 0℃; for 1h; Preparation 60; 2-Chloromethyl-3-fluoro-pyridine EPO <DP n="167"/>Dissolve <strong>[31181-79-0](3-fluoro-pyridin-2-yl)-methanol</strong> (215 mg, 1.69 mmol) in dichloromethane (10 mL) and cool to 0 0C. Add thionyl chloride (160 muL, 2.20 mmol) and stir the reaction for one hour. Add dichloromethane (50 mL) and stir the reaction with saturated aqueous sodium bicarbonate (2 x 40 mL) and brine (2 x 40 mL). Separate and dry the organic portion over magnesium sulfate, filter, and concentrate under reduced pressure to provide 198 mg (80%) of product, which is used without further purification. MS: m/z 146, 148 [C6H5ClFN + I]+; 1H NMR (300 MHz, CDCl3): delta 8.41-8.44 (m, IH), 7.41-7.47 (m, IH), 7.28-7.34 (m, IH), 4.75 (d, J = 2.0 Hz, 2H); 19F NMR (282 MHz, CDCl3): delta -123.8.
66.5% With thionyl chloride; In dichloromethane; at 0 - 20℃; for 2h; To a solution of <strong>[31181-79-0](3-fluoropyridin-2-yl)methanol</strong> (1.8 g, 13.8 mmol, 1 equiv) in DCM( 20 mL) was added SOCh ( 2.5 mL, 35 mmol, 2.5 equiv) dropwise at 0C. The resulting mixture was stirred at room temperature for 2 hours. The reaction mixture was quenched with saturated aqueous NaHCCb solution and extracted with DCM (3 * 20 mL). The combined organic layers were dried over anhydrous Na2S04 and concentrated in vacuo. The residue was purified by column chromatography (eluted with PE/EtOAc = 5/1) to afford the title compound 2-(chloromethyl)-3-fluoropyridine (1.33 g, 66.5% yield). LC-MS: m/z 146.0, 148.0 (M+H) +
  • 2
  • [ 31181-71-2 ]
  • [ 31181-79-0 ]
  • 4
  • [ 918793-01-8 ]
  • [ 31181-79-0 ]
YieldReaction ConditionsOperation in experiment
82% With hydrogen;palladium over charcoal; In methanol; for 20h; Preparation 59; (3-Fluoro-pyridin-2-yl)-methanolDissolve (6-bromo-3-fluoro-pyridin-2-yl)-methanol (850 mg, 4.13 mmol) in methanol (40 mL) then purge the solution with nitrogen. Add palladium on carbon (200 mg of 5percent wet) and stir the mixture under a hydrogen atmosphere (2 balloons) for 20 h. Filter the mixture through Celite.(R). and wash the filter cake with methanol. Concentrate the filtrate under reduced pressure and dissolve the resulting residue in chloroform (150 mL). Wash the organics with saturated aqueous sodium bicarbonate (75 mL), dry over magnesium sulfate, filter, and concentrate to give 433 mg (82percent) of the title compound which is used without further purification. 1H NMR (300 MHz, CDCl3): delta 8.40 (m, IH), 7.42-7.36 (m, IH), 7.29-7.23 (m, IH), 4.84 (s, 2H), 3.97 (br s, IH); MS (APCI): m/z 110 [C6H6FNO - H2O + H]+.
  • 5
  • [ 31181-79-0 ]
  • [ 122307-45-3 ]
  • 6
  • [ 31181-79-0 ]
  • [ 122307-46-4 ]
  • 7
  • [ 113209-81-7 ]
  • [ 31181-79-0 ]
  • 8
  • [ 31224-43-8 ]
  • ammonium chloride [ No CAS ]
  • [ 31181-79-0 ]
YieldReaction ConditionsOperation in experiment
3.78 g (93%) With sodium borohydrid; In ethanol; ethyl acetate; 2-Hydroxymethyl-3-fluoropyridine A solution of 2-formyl-3-fluoropyridine (4.0 g, 32 mmol) and sodium borohydride (309 mg, 8 mmol) in absolute ethanol (40 mL) was stirred at 0° C. for 15 minutes and at room temperature for 1 hour. The reaction was quenched with saturated aqueous ammonium chloride (5 mL) and filtered through diatomaceous earth to remove solids. The filtrate was evaporated and the resultant white solid was dissolved in ethyl acetate and water. The aqueous layer was extracted with ethyl acetate (5*30 mL) and the combined extracts were dried over anhydrous sodium sulfate. Solvent removal provided 3.78 g (93percent) of the titled product as a pale yellow oil: IR (CHCl3, cm-1) 3607, 3439, 3019, 1607, 1576, 1451, 1416, 1312, 1257, 1218, 1209, 1167, 1105, 1053, 857, 803; 1 H NMR (300 MHz, CDCl3) delta8.38 (m, 1H), 7.39 (m, 1H), 7.26 (m, 1H), 4.83 (s, 2H), 3.73 (br s, 1H); MS (FD) m/e 127 (M+);
  • 9
  • [ 31181-79-0 ]
  • [ 149463-07-0 ]
YieldReaction ConditionsOperation in experiment
With thionyl chloride; In dichloromethane; 2-chloromethyl-3- fluoropyridine hydrochloride To a solution of <strong>[31181-79-0]2-hydroxymethyl-3-fluoropyridine</strong> (3.43 g, 27 mmol) in dichloromethane (30 mL) cooled to -10° C. was added neat thionyl chloride (4.4 mL, 60 mmol) dropwise over 5 minutes. The resultant pale green solution was stirred at -10° C. for 3 hours followed by evaporation to dryness to provide 4.66 g (.95percent) of the titled product as an off-white crystalline solid: IR (CHCl3, cm-1) 2984, 1732, 1551, 1470, 1452, 1333, 1286, 1273, 1237, 1219, 1208, 1193, 1094, 905, 863, 806; 1 H NMR (300 MHz, CDCl3) delta8.69 (m, 1H), 8.06 (m, 1H), 7.89 (m, 1H), 5.09 (s, 2H); MS (FD) m/e 145 (M+ free base), 147 (M+2 free base)
  • 10
  • [ 31181-79-0 ]
  • [ 1301167-65-6 ]
  • 3-fluoro-2-[4-[1-(2-fluoroethyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]phenoxymethyl]pyridine*1.2 succinic acid [ No CAS ]
  • 11
  • [ 31181-79-0 ]
  • [ 1301167-65-6 ]
  • [ 1301168-14-8 ]
  • 12
  • [ 31181-79-0 ]
  • [ 1372891-61-6 ]
  • 13
  • [ 31181-79-0 ]
  • [ 124-63-0 ]
  • [ 1372891-55-8 ]
YieldReaction ConditionsOperation in experiment
78% With diethylamine; In dichloromethane; at 0℃; General procedure: Intermediate 18: (3,5-difluoro-2-pyridinyl)methyl methanesulfonate Intermediate 9 (3,5-difluoro-2-pyridinyl)methanol (114 mg, 0.786 mmol) was dissolved in DCM (anh) (6 mL) at 0° C. N,N-diethylethanamine (ALDRICH, 0.131 mL, 0.943 mmol) and methanesulfonyl chloride (ALDRICH, 0.067 mL, 0.864 mmol) were added. Reaction mixture was stirred at 0° C. for 1 h 30 min. Crude of reaction was partitioned between water and DCM, aqueous layer was extracted with DCM (2*10 mL). Organic layers were dried over MgSO4 (anh) and filtered. Solvent was eliminated to yield title compound (3,5-difluoro-2-pyridinyl)methyl methanesulfonate (137 mg, 0.614 mmol, 78percent yield). 1H NMR (400 MHz, DMSO-d6) delta ppm: 1H NMR (300 MHz, DMSO-d6) delta ppm: 8.58 (d, 1H), 8.06-8.11 (m, 1H), 5.36 (d, 2H), 3.27 (s, 3H). [ES+MS] m/z 224 (MH+). Intermediates 19-21 were prepared by methods analogous to that described for Intermediate 18 but replacing the alcohol ((3,5-difluoro-2-pyridinyl)methanol) with that indicated in Table 2. Reaction times varied from 1 h to 4 h.
With triethylamine; In tetrahydrofuran; at 0℃; for 2h; To a solution of <strong>[31181-79-0](3-fluoropyridin-2-yl)methanol</strong> (230 mg) and triethylamine (74 mg) in THF (5 mL) was added methanesulfonyl chloride (71 mg) at 0°C, and the reaction mixture was stirred at 0°C for 2 hr. The reaction mixture was concentrated under reduced pressure, a saturated aqueous sodium hydrogen carbonate solution was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over magnesium sulfate. The solvent was evaporated under reduced pressure to give the title compound. MS (ESI+) : [M+H]+206.2.
With triethylamine; In dichloromethane; at 0 - 20℃; The mesylate of <strong>[31181-79-0](3-fluoropyridin-2-yl)methanol</strong> (100 mg) was prepared by reaction with methanesulfonyl chloride (1 .1 eq) and triethylamine (2 eq) in DCM at 0 °C, with warming to ambient temperature. N-[1 -(Fluoromethyl)cyclopropyl]-3-[(1 -methylpyrazol-4- yl)methyl]-2,4-dioxo-1 1H-quinazoline-6-sulfonamide (100 mg, 0.260 mmol), the crude mesylate (55 mg, 0.286 mmol) and potassium carbonate (43 mg, 0.312 mmol) in DMF was conventionally heated to 70 °C for 4 h. Usual work-up afforded the desired product (15 mg, 0.030 mmol, 1 1 percent) as a white powder.
  • 14
  • [ 31181-79-0 ]
  • [ 76-05-1 ]
  • [ 173530-73-9 ]
  • ethyl 8-[(3-fluoropyridin-2-yl)methoxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylate trifluoroacetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
68% Ethyl 8-[(3-fluoropyridin-2-yl)methoxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylate trifluoroacetate 144 mg of ethyl 8-hydroxy-2-methylimidazo[1,2-a]pyridine-3-carboxylate (Example 3A, 0.65 mmol) were dissolved in 3.9 ml of THF, and 100 mg of <strong>[31181-79-0](3-fluoropyridin-2-yl)methanol</strong> (0.79 mmol), 189 mg of triphenylphosphine (0.72 mmol) and then 0.15 ml of diisopropyl azodicarboxylate (0.72 mmol) were added. The reaction mixture was stirred at RT overnight and then purified by preparative HPLC (RP18 column, mobile phase: acetonitrile/water gradient with addition of 0.1percent TFA). This gave 198 mg (68percent of theory, purity 99percent) of the target compound. LC-MS (Method 1): Rt=0.84 min
  • 15
  • [ 31181-79-0 ]
  • 4-((3-fluoropyridin-2-yl)methoxy)-2-(2-oxo-1,4-dihydroquinazolin-3(2H)-yl)benzonitrile [ No CAS ]
  • 16
  • [ 31181-79-0 ]
  • 4-((3-fluoropyridin-2-yl)methoxy)-2-(2-oxo-1,4-dihydroquinazolin-3(2H)-yl)benzoic acid [ No CAS ]
  • 17
  • [ 31181-79-0 ]
  • methyl 3-(5-hydroxy-2-methylphenyl)-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxylate [ No CAS ]
  • methyl 3-(5-((3-fluoropyridin-2-yl)methoxy)-2-methylphenyl)-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
9 mg With tri-tert-butyl phosphine; 1,1'-azodicarbonyl-dipiperidine; In tetrahydrofuran; at 100℃; for 1h;Microwave irradiation; To a solution of methyl 3-(5-hydroxy-2-methylphenyl)-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxylate (500 mg), <strong>[31181-79-0](3-fluoropyridin-2-yl)methanol</strong> (407 mg) and tri-tert-butylphosphine (809 mg) in THF (10 mL) was added 1,1'-(azodicarbonyl)dipiperidine (1009 mg), and the reaction mixture was stirred under microwave irradiation at 100°C for 1 hr. The reaction mixture was concentrated under reduced pressure, a saturated aqueous sodium hydrogen carbonate solution was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (ethyl acetate/hexane), and collected by HPLC (C18, mobile phase: water/acetonitrile (0.1percent TFA-containing system)). To the obtained fraction was added a saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give the title compound (9 mg). MS (ESI+): [M+H]+422.3.
  • 18
  • [ 31181-79-0 ]
  • methyl 4-hydroxy-2-(2-oxo-1,4-dihydroquinazolin-3(2H)-yl)benzoate [ No CAS ]
  • methyl 4-((3-fluoropyridin-2-yl)methoxy)-2-(2-oxo-1,4-dihydroquinazolin-3(2H)-yl)benzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
0.96 g To a solution of <strong>[31181-79-0](3-fluoropyridin-2-yl)methanol</strong> (0.50 g) and methanesulfonyl chloride (0.37 mL) in THF (5 mL) was added dropwise triethylamine (1.1 mL) at 0°C, and the obtained mixture was stirred at 0°C for 1.5 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was dissolved in DMF (10 mL), and methyl 4-hydroxy-2-(2-oxo-1,4-dihydroquinazolin-3(2H)-yl)benzoate (1.17 g) and potassium carbonate (1.36 g) were added. The obtained mixture was stirred at 70°C overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (0.96 g). 1H NMR (300 MHz, DMSO-d6) delta 3.66 (3H, s), 4.79 (2H, brs), 5.34 (2H, d, J = 1.9 Hz), 6.79-6.96 (2H, m), 7.02-7.25 (4H, m), 7.46-7.63 (1H, m), 7.72-7.90 (2H, m), 8.40-8.54 (1H, m), 9.48 (1H, s).
  • 19
  • [ 31181-79-0 ]
  • 2-chloro-4-(pyrimidin-5-yl)-6,7-dihydro-5H-cyclopenta[b]pyridine [ No CAS ]
  • 2-[(3-fluoropyridin-2-yl)methoxy]-4-(pyrimidin-5-yl)-6,7-dihydro-5H-cyclopenta[b]pyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
47 mg With 4,5-bis-(di-tert-butyl-phosphanyl)-9,9-dimethyl-9H-xanthene; tris(dibenzylideneacetone)dipalladium(0) chloroform complex; caesium carbonate; In toluene; at 100℃; for 5h;Inert atmosphere; Example 26 2-[(3-Fluoropyridin-2-yl)methoxy]-4-(pyrimidin-5-yl )-6,7-dihydro-5H-cyclopenta[b]pyridine To 2-chloro-4-(pyrimidin-5-yl)-6,7-dihydro-5H-cyclopen ta[b]pyridine (70 mg), <strong>[31181-79-0](3-fluoropyridin-2-yl)methanol</strong> (46 mg), t-Bu-X-Phos (31 mg), Pd2(dba)3·CHCl3 (19 mg) and cesium carbonate (295 mg) was added toluene (3 mL), and the mixture was degassed, then stirred under Ar atmosphere at 100°C for 5 hours. After the reaction mixture was allowed to return to room temperature, diluted with ethyl acetate, filtered through a short column, and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (47 mg) as a white solid. [MS (ESI) m/z 323.4 (M+H)+]
  • 20
  • [ 31181-79-0 ]
  • 2-chloro-4-(2-methylpyrimidin-5-yl)-5,6,7,8-tetrahydroquinoline [ No CAS ]
  • 2-[(3-fluoropyridin-2-yl)methoxy]-4-(2-methylpyrimidin-5-yl)-5,6,7,8-tetrahydroquinoline [ No CAS ]
YieldReaction ConditionsOperation in experiment
27 mg With 4,5-bis-(di-tert-butyl-phosphanyl)-9,9-dimethyl-9H-xanthene; tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; In toluene; at 100℃; for 11h;Inert atmosphere; Example 187 2-[(3-Fluoropyridin-2-yl)methoxy]-4-(2-methylpyrimi din-5-yl)-5,6,7,8-tetrahydroquinoline To 2-chloro-4-(2-methylpyrimidin-5-yl)-5,6,7,8-tetrahy droquinoline (60 mg), <strong>[31181-79-0](3-fluoropyridin-2-yl)methanol</strong> (38 mL), Pd2(dba)3 (21 mg), t-Bu-X-Phos (24 mg) and cesium carbonate (150 mg) was added toluene (2 mL), and the mixture was degassed, then stirred under Ar atmosphere at 100°C for 11 hours. After the reaction mixture was allowed to return to room temperature, the reaction mixture was added with water and ethyl acetate, and subjected to extraction. The organic layer was dried over anhydrous sodium sulfate, filtered off, and the filtrate was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography and by recycling preparative gel permeation chromatography (Japan Analytical Industry, Co. Ltd., LC-9201) to give the title compound (27 mg) as a white powder. [MS (ESI) m/z 351.3 (M+H)+]
  • 21
  • [ 31181-79-0 ]
  • 2-chloro-4-[(4-methoxybenzyl)oxy]-5,6,7,8-tetrahydroquinoline [ No CAS ]
  • 2-[(3-fluoropyridin-2-yl)methoxy]-4-[(4-methoxybenzyl)oxy]-5,6,7,8-tetrahydroquinoline [ No CAS ]
YieldReaction ConditionsOperation in experiment
113 mg [Step 2] Production of 2-[(3-fluoropyridin-2-yl)methoxy]-4-[(4-methoxybenz yl)oxy]-5,6,7,8-tetrahydroquinoline To 2-chloro-4-[(4-methoxybenzyl)oxy]-5,6,7,8-tetrahydr oquinoline (200 mg), <strong>[31181-79-0](3-fluoropyridin-2-yl)methanol</strong> (109 mL), Pd2(dba)3 (60 mg), t-Bu-X-Phos (67 mg) and potassium phosphate (280 mg) was added toluene (5 mL), and the mixture was degassed, then stirred under Ar atmosphere at 100°C for 4 hours. The reaction mixture was added with NaO-t-Bu (127 mg), and further stirred at 100°C for 2 hours. The solvent of the reaction mixture was evaporated under reduced pressure and the resulting residue was purified by silica gel column chromatography to give the title compound (113 mg) as red oil.
  • 22
  • [ 31181-79-0 ]
  • [ 884494-84-2 ]
  • methyl 2-((3-fluoropyridin-2-yl)methoxy)-4-iodonicotinate [ No CAS ]
YieldReaction ConditionsOperation in experiment
0.87 g With sodium hydride; In tetrahydrofuran; mineral oil; at 0℃; for 1h; To a solution of methyl 2-fluoro-4-iodonicotinate (0.70 g) obtained in Reference Example 40 and <strong>[31181-79-0](3-fluoropyridin-2-yl)methanol</strong> (0.48 g) in THF (7 mL) was added 60percent sodium hydride (0.20 g) at 0°C, and the mixture was stirred at the same temperature for 1 hr. To the reaction solution was added water at 0°C, and the mixture was diluted with ethyl acetate. The organic layer was separated, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated. The residue was purified by silica gel chromatography (hexane-ethyl acetate) to give the title compound (0.87 g). MS: [M+H]+ 389.0 1H NMR (300 MHz, CDCl3) delta 3.89 (3H, s), 5.59 (2H, d, J = 1.9 Hz), 7.24-7.32 (1H, m), 7.35 (1H, d, J = 5.5 Hz), 7.37-7.45 (1H, m), 7.81 (1H, d, J = 5.5 Hz), 8.40 (1H, dt, J = 4.7, 1.3 Hz).
  • 23
  • [ 31181-79-0 ]
  • [ 173530-73-9 ]
  • [ 1609166-02-0 ]
YieldReaction ConditionsOperation in experiment
2.15 g With cyanomethylenetributyl-phosphorane; In toluene; at 110℃; for 2h; Preparation Example 3 (0260) A mixture of 2 g of ethyl 8-hydroxy-2-methylimidazo[1,2-a]pyridine-3-carboxylate, 2 g of <strong>[31181-79-0](3-fluoropyridin-2-yl)methanol</strong>, 4 g of (tributylphosphoranyliden)acetonitrile, and 40 ml of toluene was stirred at 110° C. for 2 hours. The reaction mixture was concentrated under reduced pressure, water was added thereto, and the precipitated solid was collected by filtration. The obtained residue was purified by silica gel column chromatography to obtain 2.15 g of ethyl 8-[(3-fluoropyridin-2-yl)methoxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylate.
  • 24
  • [ 31181-79-0 ]
  • 2-(4-(1,3-dimethyl-1H-pyrazol-4-yl)-2-fluorobenzyl)-4-((3-fluoropyridin-2-yl)methoxy)-1,2-dihydro-3H-pyrrolo[3,4-c]pyridin-3-one [ No CAS ]
  • 25
  • [ 31181-79-0 ]
  • methyl 2-((3-fluoropyridin-2-yl)methoxy)-4-vinylnicotinate [ No CAS ]
  • 26
  • [ 31181-79-0 ]
  • methyl 2-((3-fluoropyridin-2-yl)methoxy)-4-formylnicotinate [ No CAS ]
  • 27
  • [ 31181-79-0 ]
  • N-[1-(fluoromethyl)cyclopropyl]-1-[(3-fluoro-2-pyridyl)methyl]-3-[(1-methylpyrazol-4-yl)methyl]-2,4-dioxoquinazoline-6-sulfonamide [ No CAS ]
  • 28
  • [ 31181-79-0 ]
  • [ 122307-44-2 ]
YieldReaction ConditionsOperation in experiment
11% With carbon tetrabromide; triphenylphosphine; In dichloromethane; at 20℃; for 22h;Inert atmosphere; A solution of 285 mg (2.242 mmol) (3-fluoropyridin-2-yl) -methanol (CAS: 31181-79-0) in dry dichloromethane (9 ml) under an argon atmosphere in an ice water bath with 882 mg (3:36 mmol) of triphenylphosphine and 1.12 of g (3:36 mmol) of carbon tetrabromide was added.The reaction mixture was stirred for 22 hours at room temperature.The solvent was evaporated and the residue was purified by flash chromatography using a prepacked silica gel cartridge: purified (mobile phase cyclohexane-ethyl acetate, gradient 15percent to 30percent)) to give 156 mg (11percent yield, 98percent pure) of the title compound received.
  • 29
  • [ 31181-79-0 ]
  • {1-[({7-[(3-fluoropyridin-2-yl)methoxy]-2,5-dimethylpyrazolo[1,5-a]pyridin-3-yl}carbonyl)amino]-2-methylpentan-2-yl}carbamic acid tert-butyl ester [ No CAS ]
  • 30
  • [ 31181-79-0 ]
  • N-(2-amino-2-methylpentyl)-7-[(3-fluoropyridin-2-yl)methoxy]-2,5-dimethylpyrazolo[1,5-a]pyridine-3-carboxamide [ No CAS ]
  • 31
  • [ 31181-79-0 ]
  • tert-butyl-4-(7-bromo-6-chloro-2-(chloromethyl)-8-fluoroquinazolin-4-yl)piperazine-1-carboxylate [ No CAS ]
  • tert-butyl 4-(7-bromo-6-chloro-8-fluoro-2-(((3-fluoropyridin-2-yl)methoxy)methyl)quinazolin-4-yl)piperazine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
77% With tetrabutylammomium bromide; sodium hydroxide; In dichloromethane; water; at 50℃; for 48h;Sealed tube; To a solution of tert-butyl 4-(7-bromo-6-chloro-2-(chloromethyl)-8-fluoroquinazolin-4- yl)piperazine-1-carboxylate (494 mg, 1 mmol), <strong>[31181-79-0](3-fluoropyridin-2-yl)methanol</strong> (381 mg, 3 mmol) and Bu4NBr (322 mg, 1 mmol) in 5 mL of DCM, 5 mL of 20percent NaOH aqueous solution was added. The resulting mixture was stirred at 50 oC in a sealed vial for 48 h. The mixture was allowed to cool to RT and partitioned between DCM and water. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified via Isolera One (MeOH/DCM = 0-10percent) to afford the desired product (450 mg.77percent yield).
  • 32
  • [ 31181-79-0 ]
  • tert-butyl (2R,5S)-4-(7-bromo-6-chloro-2-(chloromethyl)-8-fluoroquinazolin-4-yl)-2,5-dimethylpiperazine-1-carboxylate [ No CAS ]
  • tert-butyl (2R,5S)-4-(7-bromo-6-chloro-8-fluoro-2-(((3-fluoropyridin-2-yl)methoxy)methyl)quinazolin-4-yl)-2,5-dimethylpiperazine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
51% With tetrabutylammomium bromide; sodium hydroxide; In dichloromethane; at 50℃; for 48h;Sealed tube; To a solution of tert-butyl (2R,5S)-4-(7-bromo-6-chloro-2- (chloromethyl)-8-fluoroquinazolin-4-yl)-2, 5 -dimethylpiperazine- 1 -carboxylate (500mg, 0.96 mmol), <strong>[31181-79-0](3-fluoropyridin-2-yl)methanol</strong> (381 mg, 3 mmol) and Bu4NBr (322 mg, 1mmol) in DCM (5 mL), 20percent NaOH aqueous solution (5 mL) was added and the resulting mixture was stirred at 50 °C in a sealed vial for 48 h. The mixture was allowed to cool to RT and partitioned between DCM and water. The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified via Isolera One(MeOHIDCM = 0-10percent) to afford the desired product (300 mg, 51percent yield)
  • 33
  • [ 31181-79-0 ]
  • 3-(3-((6-fluoropyridin-3-yl)methyl)isoxazol-5-yl)pyridin-2-amine [ No CAS ]
  • 3-(3-((6-((3-fluoropyridin-4-yl)methoxy)pyridin-3-yl)methyl)isoxazol-5-yl)pyridin-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
57% With potassium tert-butylate; In tetrahydrofuran; for 0.5h; To a neat mixture of 3-(3-((6-fluoropyridin-3-yl)methyl)isoxazol-5-yl)pyridin-2 -amine (Intermediate E, 50 mg, O. l9mmol) and 3-fluoropyridin-2-yl)methanol (235mg, l.85mmol) was added potassium 2-methylpropane-2-olate (1M in THF, l.85mL, l.85mmol) and the mixture was stirred for 30min. The mixture was transferred to a silica gel samplet which was subsequently loaded on to a Biotage Snap column. The residue was purified by column chromatography (Si02, hexane/ethyl acetate). Combined fractions were concentrated under reduced pressure. Residue was dissolved in acetonitrile (5mL) and water (lOmL), frozen and lyophilized to yield 3-(3-((6-((3-fluoropyridin-2- yl)methoxy)pyridin-3-yl)methyl)isoxazol-5-yl)pyridin-2-amine (40mg, O.l lmmol, 57%) as a white solid. MS: 378.2 [M+H]+.
  • 34
  • [ 31181-79-0 ]
  • S-((3-fluoropyridin-2-yl)methyl)ethanethioate [ No CAS ]
  • 35
  • [ 31181-79-0 ]
  • (3-fluoropyridin-2-yl)methanesulfonyl chloride [ No CAS ]
 

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