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Structure of 247069-27-8

Chemical Structure| 247069-27-8

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Product Details of [ 247069-27-8 ]

CAS No. :247069-27-8
Formula : C5H5F2N3
M.W : 145.11
SMILES Code : FC1=C(N)N=C(N)C(F)=C1
MDL No. :MFCD03412208
InChI Key :GCIUCMRUMOAHKR-UHFFFAOYSA-N
Pubchem ID :10176199

Safety of [ 247069-27-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H319
Precautionary Statements:P305+P351+P338

Computational Chemistry of [ 247069-27-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 32.96
TPSA ?

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

64.93 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.03
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

0.36
Log Po/w (WLOGP)?

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

1.38
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.

0.87
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

0.84
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.9

Water Solubility

Log S (ESOL):?

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

-1.41
Solubility 5.64 mg/ml ; 0.0389 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.

-1.29
Solubility 7.47 mg/ml ; 0.0515 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

-1.84
Solubility 2.08 mg/ml ; 0.0144 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.

-6.93 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)

1.82

Application In Synthesis of [ 247069-27-8 ]

* 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 [ 247069-27-8 ]

[ 247069-27-8 ] Synthesis Path-Downstream   1~16

  • 1
  • [ 247069-27-8 ]
  • [ 98349-24-7 ]
  • (Z)-3-Hydroxy-3-(2,4,5-trifluoro-phenyl)-acrylic acid ethyl ester [ No CAS ]
  • (E)-1-(6-amino-3,5-difluoropyridin-2-yl)-6-fluoro-7-(3-isobutyryloxyazetidin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid [ No CAS ]
  • (Z)-1-(6-amino-3,5-difluoropyridin-2-yl)-6-fluoro-7-(3-isobutyryloxyazetidin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
EXAMPLE 7AA solution of EXAMPLE 6 (83.2Kg) in triethyl orthoformate (SO.lKg) at reflux wasstirred for 0.5-1 hour, treated with acetic anhydride (103.5Kg), stirred for 12 hours and cooledto ambient temperature to provide a solution that was used immediately.EXAMPLE 7BThe solution of EXAMPLE 7A was treated with N-methylpyrrolidinone (210Kg),acetonitrile (161Kg) and water (3Kg), added to a suspension of EXAMPLE 4 (57.4Kg) in 1:1N-methylpyrrolidinone (210Kg) and acetonitrile (161Kg), stirred for 2 hours, added to water(662Kg) and filtered. The filtrant was washed with (2:1) acetonitrile/water and water anddried under vacuum at 60C to provide 119.5Kg of product. Mp 157-160C; 'H NMR(CDC13, 300 MHz) (E) 8 1.15 (t, 3H), 4.16 (q, 2H), 4.64 (br s, 2H), 6.90 (m, 1H), 7.22 (t,1H), 7.32 (m, 1H), 9.03 (d, 1H), 12.44 (bd, 1H); (Z) 8 1.03 (t, 3H), 4.11 (q, 2H), 4.60 (br s,2H), 6.90 (m, 1H), 7.20 (t, 1H), 7.48 (m, 1H), 8.90 (d, 1H), 11.17 (bd, 1H).
  • 2
  • [ 247069-28-9 ]
  • [ 247069-27-8 ]
YieldReaction ConditionsOperation in experiment
With formic acid;20% Pd(OH)2 on carbon; In Isopropyl acetate; water; at 50℃; for 2h; A mixture of half-wet 20% palladium hydroxide on carbon (68.1 Kg) was treatedsequentially with 39.1% (w/w) EXAMPLE 3 in isopropyl acetate (410Kg total, 160KgEXAMPLE 3), isopropyl acetate (550Kg) and 88% formic acid (57Kg). The mixture wasstirred at 50C for 2 hours and filtered under nitrogen through diatomaceous earth (Celite)with isopropyl acetate (200Kg) rinsing. The filtrate was washed twice with 6% citric acidsolution having its pH adjusted to 4 with potassium hydroxide (water (200Kg)/citric acid(12Kg)/potassium hydroxide (2Kg)), 1M sodium bicarbonate solution (150Kg) and water(150Kg) and concentrated. The concentrate was treated with heptane(1005Kg) over 90minutes, and the solution was cooled to 0C and filtered. The filtrant was washed withheptane (220Kg) and dried under vacuum at 40C to provide 61.5Kg of product, which wasstored in an opaque container under nitrogen. H NMR (CDCls, 300 MHz) 8 7.03 (t, 1H),4.5-4.0 (brs, 4H).
  • 3
  • [ 2875-18-5 ]
  • [ 247069-27-8 ]
  • [ 3534-50-7 ]
  • 4
  • [ 2875-18-5 ]
  • [ 247069-27-8 ]
YieldReaction ConditionsOperation in experiment
91% With ammonium hydroxide; In ethanol; at 30℃; for 3h;Green chemistry; In a 250 mL sealed four-neck reaction flask,15.1 g of 2,3,5,6-tetrachloropyridine prepared in Example 5 and 100 mL of ethanol were added.Add 15 grams of 22% ammonia water,The end of the drop,The mixture was stirred and controlled at 30 C for 3 hours, and the reaction was completed. The organic phase was evaporated under reduced pressure to give a pale-yellow solid (1,3,5,5,6-tetrafluoropyridine, 13.2 g, yield 91.0%).
  • 5
  • [ 247069-27-8 ]
  • [ 17455-13-9 ]
  • [ 1415555-52-0 ]
YieldReaction ConditionsOperation in experiment
89% In tert-butyl methyl ether; at 22℃; for 1 - 2h; General procedure: A solution of 18-crown-6 (2.2 mmol) in methyl tert-butyl ether (5 mL) was added to a solution of polyhalogenated diaminopyridine (2.0 mmol) in the same solvent (5 mL). The mixture was kept for 1-2 h at room temperature (?22 C) upon stirring. The precipitate formed was filtered off, washed with a small amount of the cold solvent, dried in air to a constant weight, and recrystallized from CCl4.
at 5℃; for 12h; General procedure: b) A solution of 18-crown-6 (0.9 mmol) in one of the listed solvent (n-hexane, acetone, MeOH, t-BuOMe, CHCl3, CCl4, and DMAc, 25 mL) was added dropwise to a solution of arylenediamine (from 2.0 to 4.0 mmol) in the same solvent (25 mL). The mixture was kept at room temperature (~22 C) to evaporate 50-80% of the solvent volume, and at 5 C for 12 h. The precipitate formed was filtered off, washed with a small amount of the cold solvent, and dried in air to a constant weight. The chemical composition of the precipitate was analyzed using NMR spectroscopy.
  • 6
  • [ 247069-27-8 ]
  • [ 101799-75-1 ]
  • (E)-1-(6-amino-3,5-difluoropyridin-2-yl)-6-fluoro-7-(3-isobutyryloxyazetidin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid [ No CAS ]
  • (Z)-1-(6-amino-3,5-difluoropyridin-2-yl)-6-fluoro-7-(3-isobutyryloxyazetidin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid [ No CAS ]
  • 7
  • [ 247069-27-8 ]
  • [ 101799-75-1 ]
  • 1-(6-amino-3,5-difluoropyridin-2-yl)-6-fluoro-7-(3-isobutyryloxyazetidin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
7.9 g In acetonitrile; at 10 - 30℃; (2) Compound A-2 (5 g, 20.3 mmol), triethylorthoformate (10 ml) and acetic anhydride (6 ml) were mixed and stirred, and the temperature was raised to 120-130C. The mixture was stirred for 4 hours, and the reaction was completely cooled down to 15 - The mixture was stirred at 25 C, added with water (30 ml) and ethyl acetate (30 ml) for 10 minutes. The mixture was extracted with liquid and the organic phase was dried over anhydrous sodium sulfate. The organic layer was concentrated under reduced pressure and dissolved in acetonitrile (20 ml). A mixture of diamino-3,5-difluoropyridine (3.2 g, 22.3 mmol) and acetonitrile (20 ml) was added dropwise, and the temperature was controlled at 10-30C for 1-2 hours. The reaction was complete, the temperature was lowered, an appropriate amount of water was added, filtered, and dried to give 7.9 g of Compound A-3, HPLC 97.4%, and Compound 12.3%. Yield 97%.
  • 8
  • [ 247069-27-8 ]
  • [ 1493-13-6 ]
  • 3,5-difluoropyridine-2,6-diyl bis(trifluoromethanesulfonate) [ No CAS ]
  • 3,5-difluoropyridin-2-yl trifluoromethanesulfonate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium nitrite; In hexane; dimethyl sulfoxide; at 5 - 20℃; for 1h; General procedure: To a solution of hexane (5 mL), DMSO (0.5 mL), and trifluoromethanesulfonicacid (0.54 mL, 6 mmol) at 5 C were sequentially added therespective aminopyridine 1a-j (2 mmol) and NaNO2 (0.35 g, 5 mmol)under stirring and the mixture was stirred for 10 min. An immediateemission of N2 bubbles was observed. In the case of diamino derivatives1k-n, double amounts of NaNO2 and TfOH were used. The resultingmixture was then stirred for 50 min at r.t. until the startingamine had been consumed as monitored by TLC. The reaction mixturewas poured into H2O and extracted with CH2Cl2 (2 × 25 mL). Thecombined organic extracts were dried (Na2SO4), filtered, and the solventwas removed under reduced pressure on a rotary evaporator.The product was purified by silica gel flash chromatography (eluent:CH2Cl2).
  • 9
  • [ 247069-27-8 ]
  • ethyl 3-ethoxy-2-(3-chloro-2,4,5-trifluorobenzoyl)acrylate [ No CAS ]
  • ethyl 3-[(6-amino-3,5-difluoropyridin-2-yl)amino]-2-(3-chloro-2,4,5-trifluorobenzoyl)acrylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
53% In 1-methyl-pyrrolidin-2-one; acetonitrile; at 20℃; for 6h; General procedure: To a mixture of the above 5a, 5b, N-methylpyrrolidone (NMP, 80 mL) and acetonitrile (40 mL) was added a solution of <strong>[247069-27-8]3,5-difluoropyridine-2,6-diamine</strong> (29.80 g0.205 mol), NMP (30 mL) and acetonitrile (20 mL) in portions and stirred for 6 h at room temperature. The reaction mixture was poured into water (120 mL) and stirred for 2 h, and then filtered. The solid was collected by suction, washed with acetonitrile and water (v:v = 60:1), and dried in vacuo to give the title compounds 6a, 6b (37-53%, from 1a, 1b) as yellow solids.
28.4 g In 1-methyl-pyrrolidin-2-one; acetonitrile; at 20℃; for 1h; To a three-necked flask was added compound 3 (20g, 0.071mol),triethylorthoformate (18.97mL, 0.11mol) and acetic anhydride (20.21mL, 0.21mol) wasstirred and heated to reflux (~ 139 ) 3h, falls at room temperature, the reactionliquid was NMP- acetonitrile (50mL-50mL) diluted with 1mL of distilled water was addedto prepare the compound 4 directly without separation into the next reaction. Threeneckedflask was added 2,6-diamino-3,5-difluoro-pyridine (11.38g, 0.078mol), NMPacetonitrile(50mL-50mL), stirred and dissolved at room temperature, the reactionsolution was added dropwise a step, droplets Bi reaction was stirred at room temperature1h. 160mL of distilled water was added dropwise to the reaction, the precipitated lightyellow solid was filtered, followed by acetonitrile - water (48mL-24mL), water (50mL)and washed beating, 60 deg.] C and dried in vacuo to give a yellow powder 28.4g,HPLC98.4%.
7.3 g In acetonitrile; at 10 - 30℃; (2) Compound W-2 (5 g, 17.8 mmol), triethylorthoformate (8 ml) and acetic anhydride (6 ml) were mixed and stirred, and the temperature was raised to 120-130C. The mixture was stirred for 4 hours, and the reaction was completely cooled down to 15C. The mixture was stirred at 25 C, added with water (30 ml) and ethyl acetate (30 ml) for 10 minutes. The mixture was extracted with liquid and the organic phase was dried over anhydrous sodium sulfate. The organic layer was concentrated under reduced pressure and dissolved in acetonitrile (20 ml). A mixture of <strong>[247069-27-8]2,6-diamino-3,5-difluoropyridine</strong> (3.1 g, 21.4 mmol) and acetonitrile (20 ml) was added dropwise, and the temperature was adjusted to 10-30 C for 1-2 hours. The reaction was complete, the temperature was lowered, an appropriate amount of water was added, filtered, and dried to give 7.3 g of Compound W-4, HPLC 97.1%, and Compound 2 2.5%. Yield 94.1%.
  • 10
  • [ 247069-27-8 ]
  • [ 96568-05-7 ]
  • ethyl 3-[(6-amino-3,5-difluoropyridin-2-yl)amino]-2-(2,6-dichloro-5-fluoronicotinoyl)acrylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
37% In 1-methyl-pyrrolidin-2-one; acetonitrile; at 20℃; for 6h; General procedure: To a mixture of the above 5a, 5b, N-methylpyrrolidone (NMP, 80 mL) and acetonitrile (40 mL) was added a solution of <strong>[247069-27-8]3,5-difluoropyridine-2,6-diamine</strong> (29.80 g0.205 mol), NMP (30 mL) and acetonitrile (20 mL) in portions and stirred for 6 h at room temperature. The reaction mixture was poured into water (120 mL) and stirred for 2 h, and then filtered. The solid was collected by suction, washed with acetonitrile and water (v:v = 60:1), and dried in vacuo to give the title compounds 6a, 6b (37-53%, from 1a, 1b) as yellow solids.
  • 11
  • [ 247069-27-8 ]
  • [ 18621-18-6 ]
  • [ 101799-75-1 ]
  • [ 77-92-9 ]
  • [ 442526-91-2 ]
YieldReaction ConditionsOperation in experiment
93.58% Ethyl 2,4,5-trifluorobenzoylacetate (20.0 g, 0.081 mol) was added to a 250 mL reaction flask.Triethylorthoformate (21.6 mL, 0.130 mol), acetic anhydride (32.5 mL, 0.344 mol), stirring,Heating was started and the temperature of the feed was raised to 130 C. for 4.0 hours.After the reaction was completed, the solvent was distilled off under reduced pressure to obtain an oily liquid.Add 70 mL of N-methylpyrrolidone to make the oily liquidThe solution was dissolved, <strong>[247069-27-8]3,5-difluoro-2,6-diaminopyridine</strong> (13.8 g, 0.095 mol) was added, and the feed solution was warmed to 50C.Stir and stir for 1.5h. After the addition of anhydrous lithium chloride (6.12 g, 0.146 mol), DBU (11.37 g, 0.075 mol) was added, and the reaction temperature was controlled at 35 C. for 2.0 h.3-Hydroxyazetidine hydrochloride (8.45 g, 0.077 mol) was added, DBU (26.82 g, 0.176 mol) was slowly added, and the temperature was 35 C. for 2.5 h.After the reaction is complete, transfer to a 500 mL reaction flask and add 25 mL of ethyl acetate.Slowly add 145 mL of 10% citric acid solution.After the addition was completed, the temperature was adjusted to 20C, and the crystals were crystallized for 4.0 hours. The crystals were collected, and the mixture was collected by suction filtration. The cake was collected and dried in an oven at 60C to obtain 38.35 g of the intermediate I. The yield was 93.58%.
  • 12
  • [ 247069-27-8 ]
  • [ 101799-75-1 ]
  • diethyl (2Z,2'Z)-3,3'-((3,5-difluoropyridine-2,6-diyl)bis(azanediyl))bis(2-(2,4,5-trifluorobenzoyl)acrylate) [ No CAS ]
YieldReaction ConditionsOperation in experiment
4 g In water; acetonitrile; at 60 - 70℃; for 10h; (1) Compound A-2 (5 g, 20.3 mmol), triethylorthoformate (10 ml), acetic anhydride (6 ml) were mixed and stirred, and the temperature was raised to 120-130C, and the mixture was stirred for 4 hours. The reaction was completely cooled down to 15C. Acetonitrile (20 ml) was added at 25C, water (3 ml) was stirred for 10 minutes, and it was added dropwise to 2,4-diamino-3,5-difluoropyridine (1.2 g, 8.1 mmol), acetonitrile (20 ml). In the reaction flask, after completion of the dropwise addition, the temperature was raised to 60 to 70C and stirred for 10 hours. The reaction was complete, cooled, filtered and dried to give Compound 1 (4.0 g) in a yield of 75.1%. ESI-MS: [M+H]+658.
  • 13
  • [ 247069-27-8 ]
  • ethyl 3-ethoxy-2-(3-chloro-2,4,5-trifluorobenzoyl)acrylate [ No CAS ]
  • diethyl (2Z,2'Z)-3,3'-((3,5-difluoropyridine-2,6-diyl)bis(azanediyl))bis(2-(3-chloro-2,4,5-trifluorobenzoyl)acrylate) [ No CAS ]
YieldReaction ConditionsOperation in experiment
3.9 g at 60 - 70℃; for 10h; (1) Compound W-2 (5 g, 17.8 mmol), triethylorthoformate (10 ml) and acetic anhydride (6 ml) were mixed and stirred, and the temperature was raised to 120-130C. The mixture was stirred for 4 hours, and the reaction was completely cooled down to 15C. Acetonitrile (20 ml) was added at 25C, water (3 ml) was stirred for 10 minutes, and it was added dropwise to 2,4-diamino-3,5-difluoropyridine (1.0 g, 7.1 mmol) in acetonitrile (20 ml). In the reaction flask, after completion of the dropwise addition, the temperature was raised to 60 to 70C and stirred for 10 hours. The reaction was complete, cooled, filtered and dried to give compound 2 (3.9 g) in a yield of 75.6%. ESI-MS: [M+H]+727.
  • 14
  • [ 2176-62-7 ]
  • [ 247069-27-8 ]
  • 15
  • C17H13F2N3O4S2 [ No CAS ]
  • [ 247069-27-8 ]
YieldReaction ConditionsOperation in experiment
96% With sulfuric acid; at 20℃; for 1h; 500 mL of concentrated sulfuric acid was added to Compound I (Example 3 product, 412 g).After reacting at room temperature for 1 h, the LC raw material disappeared, and 1 L of saturated sodium carbonate solution was slowly added.Extract 1 L of diethyl ether twice, combine the organic phases, wash with water, wash with brine,The crude product was evaporated under reduced pressure and purified with isopropyl alcohol to yield 139 g of Compound II (yield: 96%).
  • 16
  • C13H21F2N3O4S2 [ No CAS ]
  • [ 247069-27-8 ]
YieldReaction ConditionsOperation in experiment
95% With hydrogenchloride; In water; at 20℃; for 2h; 3 L of concentrated hydrochloric acid was added to the compound I (Example 1 product, 380 g).After reacting at room temperature for 2 h, the LC raw material disappeared, diluted with 1 L of water, and allowed to stand.The obtained solid is washed with water,The crude product was dried and purified with isopropyl alcohol to give 136 g of Compound II (yield 95%).
 

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