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Product Details of [ 849217-48-7 ]

CAS No. :849217-48-7
Formula : C11H10FNO3
M.W : 223.20
SMILES Code : O=C(C1(C(NC2=CC=C(F)C=C2)=O)CC1)O
MDL No. :MFCD11226313
InChI Key :PFMAFXYUHZDKPY-UHFFFAOYSA-N
Pubchem ID :21081530

Safety of [ 849217-48-7 ]

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

Computational Chemistry of [ 849217-48-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 16
Num. arom. heavy atoms 6
Fraction Csp3 0.27
Num. rotatable bonds 4
Num. H-bond acceptors 4.0
Num. H-bond donors 2.0
Molar Refractivity 54.53
TPSA ?

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

66.4 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.57
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

1.79
Log Po/w (WLOGP)?

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

1.8
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.

1.45
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

1.75
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.67

Water Solubility

Log S (ESOL):?

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

-2.37
Solubility 0.963 mg/ml ; 0.00431 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.

-2.8
Solubility 0.351 mg/ml ; 0.00157 mol/l
Class?

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

-2.88
Solubility 0.296 mg/ml ; 0.00133 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.

-6.39 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

0.0
Bioavailability Score?

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

0.56

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)

1.39

Application In Synthesis of [ 849217-48-7 ]

* 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 [ 849217-48-7 ]

[ 849217-48-7 ] Synthesis Path-Downstream   1~8

  • 1
  • [ 849217-48-7 ]
  • [ 123-30-8 ]
  • [ 849217-60-3 ]
YieldReaction ConditionsOperation in experiment
88% With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl acetamide; will1- (3-Dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride(5.15 g, 26.9 mmol)Aminophenol (2.93 g, 26.9 mmol) and1- (4-fluorophenylcarbamoyl) cyclopropanecarboxylic acid (5.00 g, 22.4 mmol)In N, N-dimethylacetamide (30 mL).The reaction was stirred until the reaction was complete and the mixture was poured into saturated aqueous sodium bicarbonate(200 ml) and stirred for 1 hour.The residue was filtered, washed with water (50 ml) and then with chloroform (50 ml)Drying tooN- (4-fluorophenyl) -N'-(4-hydroxyphenyl) -cyclopropane-1,1-dicarboxamide(6.22 g, yield: 88%).
88% With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In ISOPROPYLAMIDE; at 20℃; for 3h; To a solution of 4-aminophenol (2.93 g, 26.9 mmol) and 1- (4-FLUORO-PHENYLCARBAMOYL)-CYCLOPROPANECARBOXYLIC acid (5.00 g, 22.4 mmol) in DMA (30 mL) was added EDCI (5.15 g, 26.9 mmol). The mixture was stirred vigorously until the reaction was complete (-3 h). With vigorous stirring, the reaction mixture was then poured into a flask containing sat. aqueous NAHCO3 solution (200 mL). The stirring was continued for 1 h. The resulting suspension was then filtered. The solid was washed with water (50 mL), chloroform (50 ML) and dried under vacuum, affording 1- (4-FLUORO- phenylcarbamoyl) -cyclopropanecarboxylic acid (6.22g, 88% yield) as a powder (>95% purity by HPLC AND 1H NMR).
87.9% With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃; for 3h; General procedure: To a solution of the intermediate 9 (1.0g, 4.48mmol) and substituted aminophenol (5.38mmol) in DMF (15mL) was added EDCI (1.03g, 5.38mmol). The solution was stirred at room temperature for 3h. Then water (50mL) was added to precipitate white solid, adjusting pH to 4.0-5.0 by 1M HCl. The white solid was filtered off, washed and dried in vacuum to afford 10a-b [45]. 5.3.1 N-(4-fluorophenyl)-N-(4-hydroxyphenyl)cyclopropane-1,1-dicarboxamide (10a) Yield: 87.9%; MS (ESI) m/z: 315.4 [M+H]+. 1H NMR (400MHz, DMSO-d6) delta: 10.17 (s, 1H, CONH), 9.73 (s, 1H, CONH), 9.23 (s, 1H, OH), 7.83-6.68 (m, 8H, Ar-H), 1.48 (s, 4H, CH2CH2).
85% With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl acetamide; at 20℃; for 4h; General procedure: To a solution of 3a-k (6.40 mmol) in MeOH/H2O (30 mL,1:1=V:V), lithium hydroxide (230 mg, 9.6 mmol) was added, whichwas stirredat room temperature for 2 h. The pH value was then adjustedto 3 with dilute hydrochloric acid, and a large amount of solid wasprecipitated, which was filtered and dried to give an off-white solid (4a-k). The next step was carried out without purification of these products.A mixture of 4a-k (1 mmol), aminophenol (1 mmol), and 3-(ethyliminomethyleneamino)-N,N- dimethyl-propan-1-amine (1 mmol) in 10 mLDMA, was stirred at room temperature for 4 h. The reaction mixturewas monitored by TLC. After the starting material disappeared, thewater was added and the product was extracted with ethyl acetate andthe solvent was then evaporated. Finally, the product was separated bycolumn chromatography to give a pure product (5a-k).

  • 2
  • [ 168268-00-6 ]
  • [ 849217-48-7 ]
  • [ 849217-57-8 ]
YieldReaction ConditionsOperation in experiment
98% With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 1h; Toa stirred mixture of 4-benzyloxy-3-fluoro-phenylamine (33.7 g, 155.3mmol),1-(4-fluoro-phenylcarbamoyl)-cyclopropanecarboxylic acid (38.13 g, 170.8mmol)and anhydrous dichloromethane (600 ml) was added EDCI (44.7 g, 233.9mmol) inportions. After stirring at RT for 1 h, the reaction mixture was diluted withsaturated sodium bicarbonate (400 ml) and stirred for 30 minutes. Theprecipitate was filtered and air dried to give the 1st crop of product. Thebiphasic filtrate was separated, and the organic phase was washed with brine(300 ml), dried over sodium sulfate, and concentrated. The residue was taken upin DCM (100 ml), stirred for 15 minutes, and filtered to give a 2nd crop ofproduct. The combined yield of cyclopropane-1,1-dicarboxylicacid(4-benzyloxy-3-fluoro-phenyl)-amide(4-fluoro-phenyl)-amide was 64.5 g(98%). Cyclopropane-1,1-dicarboxylic acid(4-benzyloxy-3-fluoro-phenyl)-amide(4-fluoro-phenyl)-amide, yield 64.5 g (98%)
98% With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 1h; To a stirred mixture of 4-benzyloxy-3-fluoro-phenylamine (33.7 g, 155.3mmol), 1-(4-fluoro-phenylcarbamoyl)-cyclopropane carboxylic acid (38.13 g, 170.8mmol) and anhydrous DCM (600 ml) was added EDCI (44.7 g, 233.9mmol) in portions. After stirring at r.t. for 1 h, the reaction mixture was diluted with saturated sodium bicarbonate (400 ml) and stirred for 30 minutes. The precipitate was filtered and air dried to give the 1st crop of product. The biphasic filtrate was separated, and the organic phase was washed with brine (300 ml), dried over anhydrous sodium sulfate, and concentrated. The residue was taken up in DCM (100 ml), stirred for 15 minutes, and filtered to give a 2nd crop of product. The combined yield of Cyclopropane-1,1-dicarboxylic acid (4-benzyloxy-3-fluoro-phenyl)-amide(4-fluoro-phenyl)-amide 64.5 g, yield: 98%. 1H-NMR (300MHz, CDCl3) delta: 8.9 (m, 2H), 7.35-7.18 (m, 8H), 6.95-6.85 (m, 4H), 5.03 (s,2H), 1.53(s, 2H).
98% With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 1h; To a stirred mixture of 4-benzyloxy-3-fluoro-phenylamine (155.3 mmol, 33.7 g), 1- (4-FLUORO-PHENYLCARBAMOYL)-CYCLOPROPANECARBOXYLIC acid (170.8 mmol, 38.13 g) and anhydrous dichloromethane (600 ml) was added EDCI (233.9 mmol, 44.7 g) in portions. After stirring at RT for 1 hr, the reaction mixture was diluted with saturated sodium bicarbonate (400 ml) and stirred for 30 minutes. The precipitate was filtered and air dried to give the 1ST CROP of product. The biphasic filtrate was separated, and the organic phase was washed with brine (300 ml), dried over sodium sulfate, and concentrated. The residue was taken up in DCM (100 ml), stirred for 15 minutes, and filtered to give a 2ND crop of product. The combined yield of cyclopropane-1, 1- dicarboxylic acid (4-benzyloxy-3-fluoro-phenyl) -amide (4-fluoro-phenyl) -amide was 64.5 g (98%).
  • 3
  • [ 849217-48-7 ]
  • [ 1350377-66-0 ]
  • N-(4-(3-amino-1H-indazol-4-yl)-3-methoxyphenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide [ No CAS ]
  • 4
  • [ 849217-48-7 ]
  • [ 1350377-66-0 ]
  • C24H28BFN2O5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In dichloromethane; at 0 - 20℃; General procedure: To a mixture of 6d (40 mg, 0.178 mmol) and 7 (40 mg, 0.178 mmol) dissolved in 3 mL of DCM in ice-bath, HATU (122 mg, 0.320 mmol) was added. After stirring for 10 min, TEA (25 μL, 0.178 mmol) was dropped. The reaction was warmed to the room temperature and stirred overnight. After the completion of the reaction, the mixture was diluted with DCM (40 mL) and washed with water (3 * 20 mL) followed by brine (20 mL), dried over sodium sulfate, filtered, and evaporated. The crude product was purified by chromatograph (0-3% MeOH/DCM) to give the title compound 8d as a white solid (55 mg, 72%).
  • 5
  • [ 849217-48-7 ]
  • [ 1218790-22-7 ]
  • C27H28BFN2O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In dichloromethane; at 0 - 20℃; General procedure: To a mixture of 6d (40 mg, 0.178 mmol) and 7 (40 mg, 0.178 mmol) dissolved in 3 mL of DCM in ice-bath, HATU (122 mg, 0.320 mmol) was added. After stirring for 10 min, TEA (25 muL, 0.178 mmol) was dropped. The reaction was warmed to the room temperature and stirred overnight. After the completion of the reaction, the mixture was diluted with DCM (40 mL) and washed with water (3 * 20 mL) followed by brine (20 mL), dried over sodium sulfate, filtered, and evaporated. The crude product was purified by chromatograph (0-3% MeOH/DCM) to give the title compound 8d as a white solid (55 mg, 72%). 4.7.21 N-(4-(3-Amino-1H-indazol-4-yl)naphthalen-1-yl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (31) First, the key intermediate 30 was prepared by treating compounds 29 and 6d according to a procedure similar to that of preparation of compound 8d. The title compound 31 was then prepared as a white solid from 17 and 30 following a procedure similar to that of preparation of compound 28d in 38% yield in two steps. Mp: 184-186 C. 1H NMR (300 MHz, DMSO-d6) delta: 11.76 (s, 1H), 10.73 (s, 1H), 10.25 (s, 1H), 8.11 (d, J = 8.4 Hz, 1H), 7.89 (d, J = 7.8 Hz, 1H), 7.68 (dd, J = 8.3, 4.9 Hz, 2H), 7.62-7.55 (m, 1H), 7.52-7.43 (m, 3H), 7.39-7.34 (m, 2H), 7.19 (t, J = 8.8 Hz, 2H), 6.84 (dd, J = 4.5, 3.3 Hz, 1H), 3.78 (s, 2H), 1.70-1.60 (m, 4H); 13C NMR (126 MHz, DMSO-d6) delta: 169.2, 158.4 (d, J = 240.7 Hz), 148.2, 141.6, 134.9 (d, J = 2.3 Hz), 134.2, 133.4, 133.0, 132.2, 127.8, 126.7, 126.6, 126.3 (2), 126.1, 122.8, 122.7 (d, J = 7.6 Hz), 121.3, 120.0, 115.2 (d, J = 22.1 Hz), 112.3, 109.3, 30.3, 16.6; MS (ESI, m/z): 480.3 [M+H]+; HRMS (ESI) calcd for C28H22FN5NaO2 [M+Na]+: 502.1655; found: 502.1646.
  • 6
  • [ 849217-48-7 ]
  • [ 1218790-22-7 ]
  • N-(4-(3-amino-1H-indazol-4-yl)naphthalen-1-yl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide [ No CAS ]
  • 7
  • [ 849217-48-7 ]
  • [ 849217-60-3 ]
  • 8
  • [ 6914-71-2 ]
  • [ 849217-48-7 ]
 

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