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Structure of 198967-24-7

Chemical Structure| 198967-24-7

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Product Details of [ 198967-24-7 ]

CAS No. :198967-24-7
Formula : C9H10FNO2
M.W : 183.18
SMILES Code : O=C(N(OC)C)C1=CC=CC=C1F
MDL No. :MFCD02684304
InChI Key :WWEPCBKULBKDCS-UHFFFAOYSA-N
Pubchem ID :18357556

Safety of [ 198967-24-7 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Computational Chemistry of [ 198967-24-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 6
Fraction Csp3 0.22
Num. rotatable bonds 3
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 45.38
TPSA ?

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

29.54 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.05
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

1.53
Log Po/w (WLOGP)?

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

1.88
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.

2.2
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

1.78

Water Solubility

Log S (ESOL):?

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

-2.08
Solubility 1.51 mg/ml ; 0.00826 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.

-1.76
Solubility 3.19 mg/ml ; 0.0174 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

-2.48
Solubility 0.611 mg/ml ; 0.00333 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.

-6.33 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)

1.73

Application In Synthesis of [ 198967-24-7 ]

* 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 [ 198967-24-7 ]

[ 198967-24-7 ] Synthesis Path-Downstream   1~20

  • 1
  • [ 6638-79-5 ]
  • [ 393-52-2 ]
  • [ 198967-24-7 ]
YieldReaction ConditionsOperation in experiment
90% Triethylamine (5.32 mL, 37.84 mmol) was added dropwise to a solution of Nu,Omicron-dimethylhydroxylamine hydrochloride (2.768 g, 28.38 mmol) in anhydrous dichloromethane (45 mL) at 0 C. After stirring for 10 min, 2-fluorobenzoyl chloride (0.303 mL, 2.52 mmol) in anhydrous dichloromethane (15 mL) was added dropwise. The reaction mixture was returned to room temperature and stirred for 5 h. The reaction mixture was quenched with water (60 mL) and the products were extracted with dichloromethane (2 x 60 mL). The combined organic phases were washed with brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. Purification using flash chromatography (silica gel, hexanes:ethyl acetate, gradient 93:7 to 60:40) afforded 2-Fluoro-N-methoxy-N-methyl-benzamide (3.1 16, 17 mmol) in a 90% yield. [0
90% Triethylamine (5.32 mL, 37.8 mmol) was added dropwise to a solution of N,O-dimethylhydroxylamine hydrochloride (2.77 g, 28.4 mmol) in anhydrous dichloromethane (45 mL) at 0 C. After stirring for 10 min, 2-flurobenzoyl chloride (0.303 mL, 2.52 mmol) in anhydrous dichloromethane (15 mL) was added dropwise. The reaction mixture was returned to room temperature and stirred for 5 h. The reaction mixture was quenched with water (60 mL) and the products were extracted with dichloromethane (2 * 60 mL). The combined organic phases were washed with brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. Purification using flash chromatography (silica gel, hexanes/ethyl acetate, gradient 93:7 to 60:40) afforded 2-Fluoro-N-methoxy-N-methyl-benzamide (3.12 g, 17.0 mmol, 90% yield). 1H NMR (500 MHz, CDCl3): delta 7.44-7.38 (2H, m), 7.19 (1H, t, J = 7.5 Hz), 7.10 (1H, t, J = 8.9 Hz), 3.55 (3H, br s), 3.35 (3H, br s). 13C NMR (125 MHz, CDCl3): delta 166.40, 158.66, (d, J = 249 Hz), 131.50, 128.90, 124.11, 123.52 (d, J = 17 Hz), 115.69 (d, J = 21 Hz), 61.21, 32.31. 19F NMR (470 MHz, CDCl3): delta -114.04 (1F, s). HRMS (ESI) calculated for C9H10FNO2H+ (M+H)+ 184.07683, found 184.07702.
62% With pyridine; In tetrahydrofuran; at 0 - 20℃; for 2.25h; N,O-Dimethylhydroxylamine hydrochloride (23.4 g, 240 mmol) was suspended inTHF (100 ml) and cooled to 0 C under nitrogen. Pyridine (32 ml, 400 mmol) was addedslowly. A solution of 2-fluorobenzoyl chloride (9.5 ml, 80 mmol) in THF (50 ml) was addedover 15 min. The reaction was removed from the ice bath and stirred at rt for 2 h. Water (100ml) and AcOEt (100 ml) were added, and the phases were separated. The aq. phase wasextracted with AcOEt (100 ml). The organic phases were pooled and washed with 1 N HCI (2x 100 ml) and 1 N NaOH (100 ml). After drying over MgSO4, the sample was concentrated toyield a yellow oil (10.7 g). The oil was purified by vacuum distillation, and a colorless oil wascollected (0.22 torr, 57-59 C, 9.1 g, 62% yield)2-fluoro-N-methoxy-N-methylbenzamide1H-NMR (300MHz, CDCI3) 53.34 (s, 3H), 3.54 (br, 3H), 7.10 (m, 1H), 7.19 (m, 1H),7.42 (m, 2H)
  • 2
  • [ 198967-24-7 ]
  • C24H24ClFN2O4S [ No CAS ]
YieldReaction ConditionsOperation in experiment
Example 48: 4-tert-Butyl-N-[5-chloro-2-(2-fluoro-benzoyi)-pyridin-3-yl]- benzenesulfonamide; [00439] N-(2-Bromo-5-chloro-pyridin-3-yl)-4-tert-butyl-N-methoxymethyl- benzenesulfonamide (140 mg, 300 mmol) was placed in a dry 2-neck 10 mL round-bottom flask. The flask was evacuated and purged with nitrogen, followed by the addition of THF (1 mL). The homogeneous mixture was lowered to -5 C and /PrMgCI (0.33 mL, 2.0 M) was added dropwise. Upon completion of the addition, the reaction was stirred 90 minutes, followed by the slow addition of 2- fluoro-N-methoxy-N-methyl-benzamide (140 mg, 750 mmol). The reaction was stirred overnight, during which the ice-bath warmed to room temperature. The following day, the reaction was quenched with a small quantity of MeOH and the solvents evaporated in vacuo. The residue was subsequently treated with 4.0 M HCI (in dioxane) (1 mL, 4.0 mmol) and H2O (0.33 mL), and then stirred at 80 C for two hours. The resultant solution was diluted with EtOAc, washed with water, saturated sodium bicarbonate, and brine; dried with MgSO4, and evaporated employing reduced pressure. The crude sulfonamide was finally purified via preparatory TLC (20% EtOAc/hexanes) and recrystallization from MeCN/H2O to afford 98 mg of the title compound: 1H NMR (400 MHz, CDCI3) delta 10.6 (s, 1 H), 8.3 (d, 1H), 8.2 (d, 1H), 7.74 (d, 2H), 7.6 (d, 1 H), 7.5 (d, 1 H), 7.43 (d, 2H), 7.42-7.37 (m, 2H), 1.26 (s, 9H); MS (ES) M+H expect 447.1 , found 447.5.
  • 3
  • [ 198967-24-7 ]
  • 3-bromo-2-(diethoxymethyl)-benzo[b]furan [ No CAS ]
  • 2-(diethoxymethyl)-3-(2-fluorobenzoyl)-benzo[b]furan [ No CAS ]
YieldReaction ConditionsOperation in experiment
With tert.-butyl lithium; In n-heptane; water; toluene; EXAMPLE 13 2-(Diethoxymethyl)-3-(2-fluorobenzoyl)-benzo[b]furan To a solution of 3 g of 3-bromo-2-(diethoxymethyl)-benzo[b]furan in 80 ml of dry ether under nitrogen at -100 C was added 17.4 ml of a 1.7 M solution of tert-butyllithium in hexanes. The solution was stirred at the low temperature for 2 h then a solution of 2.76 g of <strong>[198967-24-7]N-methoxy-N-methyl-2-fluorobenzamide</strong> in 20 ml of dry ether was added and the solution stirred at the low tempertature for 10 min. The solution was then allowed to slowly warm to 0 C., water was added and the organic layer was separated, washed with water and dried over sodium sulfate and evaporated. Gravity chromatography eluding 0 to 50% toluene in heptane afforded 0.91 g of 2-(diethoxymethyl)-3-(2-fluorobenzoyl)-benzo[b]furan as an oil, 1 H-NMR (200 MHz, CDCl3) d 5.76 (CHOEt). In a similar manner were prepared: 2-(Diethoxymethyl)-5-(2-fluorobenzoyl)-thiophene, starting from 2-bromo-5-(diethoxymethyl)-thiophene (see D. J. Chadwick, J. Chambers, P. K. Hodgson, G. D, Meakins and R. L. Snowden, J. Chem. Soc., Perkin Trans. 1, 1994, 2735), 1 H-NMR (200 MHz, CDCl3) d 5.75 (CHOEt),
  • 4
  • [ 198967-24-7 ]
  • [ 108-36-1 ]
  • [ 698982-90-0 ]
  • 5
  • [ 198967-24-7 ]
  • [ 106-37-6 ]
  • [ 59396-43-9 ]
  • 6
  • [ 393-52-2 ]
  • [ 1117-97-1 ]
  • [ 198967-24-7 ]
YieldReaction ConditionsOperation in experiment
84.6% With triethylamine; In dichloromethane; at 0 - 20℃; To a solution of 2-fluorobenzoyl chloride (50 g, 0.31 mol) in CH2Cl2 (200 mL) was added N,O-dimethylhydroxylamine (46 g, 0.47 mol), and a solution of triethylamine (127 g, 1.26 mol) in CH2Cl2 (100 mL) at 0 C. The reaction mixture was warmed slowly to rt, and stirred for 3 h. The mixture was quenched with iced water and extracted with CH2Cl2 (200 mL). The organic layer was dried over Na2SO4, filtered, and concentrated to afford 2-fluoro-N-methoxy-N-methylbenzamide (48 g, yield: 84.6%).
  • 7
  • [ 198967-24-7 ]
  • [ 1826-67-1 ]
  • [ 89638-21-1 ]
YieldReaction ConditionsOperation in experiment
58.4% In tetrahydrofuran; at -78 - 20℃; A solution of <strong>[198967-24-7]2-fluoro-N-methoxy-N-methylbenzamide</strong> (16 g, 87.4 mmol) in THF (150 mL) was cooled to -78 C. Vinylmagnesium bromide (120 mL, 120 mmol) was slowly added, and the mixture stirred at -78 C. for 10 min, slowly warmed to rt, and stirred for another 3 h. The reaction mixture was quenched with 1 N aq HCl (100 mL) at 0 C. The aqueous layer was extracted with EtOAc (100 mL). The combined organic phase was washed with brine (50 mL), dried over Na2SO4, and concentrated. The residue was purified by column chromatography to afford 1-(2-fluorophenyl)-prop-2-en-1-one (7.6 g, yield: 58.4%) as a colorless oil.
  • 8
  • [ 198967-24-7 ]
  • C8H12O3(2-)*Li(1+)*Na(1+) [ No CAS ]
  • [ 1394949-24-6 ]
  • 9
  • [ 198967-24-7 ]
  • [ 141-32-2 ]
  • (E)-butyl 3-(2-(methoxy(methyl)carbarmoyl)-3-fluorophenyl)acrylate [ No CAS ]
  • (Z)-butyl 3-(2-(methoxy(methyl)carbarmoyl)-3-fluorophenyl)acrylate [ No CAS ]
  • 10
  • [ 198967-24-7 ]
  • [ 1458033-38-9 ]
  • 11
  • [ 198967-24-7 ]
  • [ 626-39-1 ]
  • [ 1458033-50-5 ]
YieldReaction ConditionsOperation in experiment
50% Tert-butyllithium in pentane (1.6M, 7.72 mL) was added dropwise to a solution of 1 ,3,5 tribromobenzene (0.972 g, 3.09 mmol) in anhydrous ether (30 mL) at -78 C under a flow of nitrogen gas. After 2 h, 2-Fluoro-/V-methoxy-/V- methyl-benzamide (1.132 g, 6.18 mmol) dissolved in anhydrous ether (5 mL) was added dropwise and the reaction mixture was allowed to slowly come to room temperature and stirred for 24 h. After 24 h, the reaction mixture was quenched with water (30 ml_) and the products were extracted with ether (2 x 50 ml_). The combined organic phases were washed with brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. Purification using flash chromatography (silica gel, hexanes:ethyl acetate, gradient 95:5 to 60:40) afforded 2-1 ,3-bis(2-fluoro-benzoyl)-5-bromobenzene 10 (0.617 g, 6.18 mmol) in a 50% yield.
  • 12
  • [ 198967-24-7 ]
  • 1,3-bis(3-fluorobenzoyl)-5-bromobenzene thiosemicarbazone [ No CAS ]
  • 13
  • [ 198967-24-7 ]
  • [ 626-39-1 ]
  • 1,3-bis(3-fluorobenzoyl)-5-bromobenzene [ No CAS ]
YieldReaction ConditionsOperation in experiment
50% tert-Butyllithium in pentane (1.6 M, 7.72 mL) was added dropwise to a solution of 1,3,5-tribromobenzene (0.972 g, 3.09 mmol) in anhydrous ether (30 mL) at -78 C under a flow of nitrogen gas. After 2 h, <strong>[198967-24-7]2-fluoro-N-methoxy-N-methyl-benzamide</strong> (1.132 g, 6.18 mmol) dissolved in anhydrous ether (5 mL) was added dropwise and the reaction mixture was allowed to slowly come to room temperature and stirred for 24 h. After 24 h, the reaction mixture was quenched with water (30 mL) and the products were extracted with ether (2 * 50 mL). The combined organic phases were washed with brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. Purification using flash chromatography (silica gel, hexanes/ethyl acetate, gradient 95:5 to 60:40) afforded 1,3-bis(3-fluorobenzoyl)-5-bromobenzene (0.617 g, 6.18 mmol, 50% yield). 1H NMR (500 MHz, CDCl3): delta 8.16 (2H, m), 8.12 (1H, pentet, J = 1.4 Hz), 7.61-7.56 (4H, m), 7.30 (2H, td, J = 7.5 Hz, 1.0 Hz), 7.20-7.16 (2H, m). 13C NMR (125 MHz, CDCl3): delta 191.23, 160.40 (d, J = 254 Hz), 139.67, 133.61, 134.29 (d, J = 8.6 Hz), 131.12 (d, J = 1.9 Hz), 129.31, 125.79 (d, J = 13.8 Hz), 124.79 (d, J = 3.8 Hz), 123.18, 116.70 (d, J = 21 Hz). 19F NMR (470 MHz, CDCl3): delta -109.73 to -109.78 (1F, m). HRMS (ESI) calculated for C20H11BrF2O2H+ (M+H)+ 400.99833, found 400.99857.
  • 14
  • [ 6638-79-5 ]
  • [ 445-29-4 ]
  • [ 198967-24-7 ]
YieldReaction ConditionsOperation in experiment
73% With N-ethyl-N,N-diisopropylamine; HATU; In dichloromethane; at 20℃; for 2h; 2-Fluoro-N-methoxy-N-methylbenzamide was prepared in 73% yield according to the Example 1 , Step A substituting 6-bromopicolinic acid for 2-fluorobenzoic acid.
  • 15
  • [ 198967-24-7 ]
  • [ 107-30-2 ]
  • [ 925211-28-5 ]
  • 16
  • [ 198967-24-7 ]
  • [ 593-71-5 ]
  • [ 18156-74-6 ]
  • 2-chloro-1-(2-fluorophenyl)-N-methoxy-N-methyl-1-[(trimethylsilyl)oxy]ethanamine [ No CAS ]
  • 17
  • [ 198967-24-7 ]
  • [ 218601-55-9 ]
  • C23H28FNO3 [ No CAS ]
  • C23H28FNO3 [ No CAS ]
  • 18
  • [ 198967-24-7 ]
  • [ 65864-64-4 ]
  • [ 1378683-82-9 ]
  • 19
  • [ 198967-24-7 ]
  • (Z)-1-(2-fluorophenyl)pent-4-en-1-one O-methyl oxime [ No CAS ]
  • (E)-1-(2-fluorophenyl)pent-4-en-1-one O-methyl oxime [ No CAS ]
  • 20
  • [ 5162-44-7 ]
  • [ 198967-24-7 ]
  • [ 1338961-41-3 ]
 

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