144851-82-1|Methyl 2-amino-3-fluorobenzoate| Ambeed

Size	Price	VIP Price	US Stock	Global Stock	In Stock
{[ item.pr_size ]}		Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}

US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days

{[ item.pr_size ]}

In Stock

- +

Please Login or Create an Account to: See VIP prices and availability

US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks

Quality Control of [ 144851-82-1 ] Purity: 95% SDS Specification

COA

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

NMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

CNMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

HPLC

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

LC-MS

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

1-2 Day Shipping
High Quality
Technical Support

Product Details of [ 144851-82-1 ]

CAS No. :	144851-82-1
Formula :	C₈H₈FNO₂
M.W :	169.15
SMILES Code :	NC1=C(C(=O)OC)C=CC=C1F
MDL No. :	MFCD11870179
InChI Key :	ISLOQGNBENYQQF-UHFFFAOYSA-N
Pubchem ID :	19432023

Safety of [ 144851-82-1 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H332-H335
Precautionary Statements:	P261-P280-P305+P351+P338

Computational Chemistry of [ 144851-82-1 ] Show Less

Physicochemical Properties

Num. heavy atoms	12
Num. arom. heavy atoms	6
Fraction Csp3	0.12
Num. rotatable bonds	2
Num. H-bond acceptors	3.0
Num. H-bond donors	1.0
Molar Refractivity	42.08
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	52.32 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.89
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	1.98
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	1.62
Log P_o/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.	1.75
Log P_o/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	1.4
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.73

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.37
Solubility	0.715 mg/ml ; 0.00423 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.	-2.7
Solubility	0.334 mg/ml ; 0.00197 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	-2.39
Solubility	0.692 mg/ml ; 0.00409 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.	-5.93 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	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)	1.36

Application In Synthesis of [ 144851-82-1 ]

* 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 [ 144851-82-1 ]

[ 144851-82-1 ] Synthesis Path-Downstream 1~35

1
[ 144851-82-1 ]
[ 1779-49-3 ]
[ 1126475-29-3 ]

Yield	Reaction Conditions	Operation in experiment
		A suspension of methyl triphenylphosphonium bromide (2.4 eq) and sodium amide (3.2 eq) in toluene (0.1 M) was stirred at RT for 3 h. After cooling down to 00C, a solution of Dl in toluene (0.1 M) was added to the suspension and the reaction mixture was heated to 500C for 3 h. 30 min. Then, The precipitate was filtered off and the solvent was evaporated under reduced pressure giving a crude that was purified by flash chromatography on silicagel, using AcOEt/PE (7:3) as solvent, affording the title compound as a yellow powder.1U NMR (500 MHz, CDCl3) delta: 7.78-7.68 (m, 6H), 7.62-7.54 (m, 3H), 7.52-7.45 (m, 7H), 6.97-6.89 (m, IH), 6.56-6.48 (m, IH), 5.76 (bs, 2H), 4.32-4.20 (m, IH). MS (ES) C26H2iFNOP requires: 413, found: 414 (M+H)+.

References: [1]Patent: WO2009/27730,2009,A1 .Location in patent: Page/Page column 55.

2
[ 67-56-1 ]
[ 825-22-9 ]
[ 144851-82-1 ]

Yield	Reaction Conditions	Operation in experiment
80%	With sulfuric acid; for 66h;Heating;	Intermediate 10. A solution of 2-amino-3-fluorobenzoic acid (559 mg, 3.62 mmol) and 1.7 mL of concentrated H2S04 in 11 mL of anhydrous methanol was heated for 66 hours. After cooling to room temperature, methanol was concentrated under reduced pressure. Residue was taken up in 30 mL of water and added to a separatory funnel. Solid sodium carbonate was added slowly until gas evolution ceased (pH 9-10). Aqueous layer was extracted with ethyl acetate (3x40 mL). The combined organic layers were washed with 100 mL sat. NaHC03(aq) and 100 mL of Brine, separated, dried (MgS04), filtered, and concentrated under reduced pressure. Column chromatography (5% Ethyl Acetate in Hexanes) yielded intermediate 10 (491 mg, 80%) as a white solid.1H-NMR (CDC13, 300 MHz): delta 7.66-7.63(m, 1H), 7.15-7.08 (m, 1H), 6.60-6.55 (m, 1H), 5.40 (br s, 2H), 3.89 (s, 3H),LCMS m/z [M+H]+ C8H8FN02 requires: 170.05. Found 170.10
80%	With sulfuric acid; for 66h;Heating;	Example 104 Preparation of Intermediate 106 [0808] [0809] A solution of 2-amino-3-fluorobenzoic acid (559 mg, 3.62 mmol) and 1.7 mL of concentrated H2SO4 in 11 mL of anhydrous methanol was heated for 66 hours. After cooling to room temperature, methanol was concentrated under reduced pressure. The residue was taken up in 30 mL of water and added to a separatory funnel. Solid sodium carbonate was added slowly until gas evolution ceased (pH 9-10). The aqueous layer was extracted with ethyl acetate (3×40 mL). The combined organic layers were washed with 100 mL sat. NaHCO300 and 100 mL of brine, separated, dried (MgSO4), filtered, and concentrated under reduced pressure. Column chromatography (5% ethyl acetate in hexanes) yielded intermediate 106 (491 mg, 80%) as a white solid. [0810] 1H-NMR (CDCl3, 300 MHz): delta 7.66-7.63 (m, 1H), 7.15-7.08 (m, 1H), 6.60-6.55 (m, 1H), 5.40 (br s, 2H), 3.89 (s, 3H), [0811] LCMS m/z [M+H]+ C8H8FNO2 requires: 170.05. Found 170.10
	With hydrogenchloride; for 2h;Heating / reflux;	2-amino-3-fluoro benzoic acid was dissolved in HCl (3 M solution in MeOH). The reaction mixture was heated to reflux for 2 h. Then, solvent was evaporated and the residue was partitioned between DCM and sat. sol. NaHCO3. The aqueous phase was separated and extracted several times withn DCM. The combined organic layers were dried (Na2SO4) and solvent was evaporated under reduced pressure to afford the title compound as a yellow oil.1H NMR (300 MHz, CDCl3) delta: 7.72-7.58 (m, IH), 7.18-7.02 (m, IH), 6.65-6.48 (m, IH), 3.88 (s, 3H). MS (ES) C8H8FNO2 requires: 169, found: 170 (M+H)+.

References: [1]Patent: WO2011/163518,2011,A1 .Location in patent: Page/Page column 158.
[2]Patent: US2013/273037,2013,A1 .Location in patent: Paragraph 0808-0811.
[3]Journal of Medicinal Chemistry,2015,vol. 58,p. 1630 - 1643.
[4]Patent: WO2009/27730,2009,A1 .Location in patent: Page/Page column 55.
[5]Chemical Communications,2018,vol. 54,p. 12766 - 12769.

3
[ 144851-82-1 ]
[ 124-63-0 ]
[ 1353628-13-3 ]

Yield	Reaction Conditions	Operation in experiment
74%	With pyridine; In dichloromethane; at 0 - 20℃; for 40h;	Intermediate 11.To a mixture of <strong>[144851-82-1]methyl 2-amino-3-fluorobenzoate</strong> (intermediate 10) (334 mg, 1.97 mmol) and pyridine (0.41 mL, 4.95 mmol) in 5.5 mL of dichloromethane at 0 C, was added slowly methanesulfonyl chloride (0.40 mL, 4.95 mmol). Mixture was warmed to room temperature and stirred overnight. HPLC indicated -48% conversion to desired product.Pyridine (0.55 mL) and 0.50 mL of methanesulfonyl chloride (approximately 6.8 mmol each) was then added at room temperature. After a total of 40 hours, reaction mixture was quenched with 10 mL of IN HCl. After 5 minutes of stirring, mixture was poured into 20 mL of water. Aqueous layer was extracted with ethyl acetate (3x30 mL). The combined organic layers were washed with 100 mL of IN HCl (aq) and 100 mL Brine, separated, dried (MgS04), filtered, and concentrated under reduced pressure. Column chromatography (15-50% Ethyl Acetate in Hexanes) yielded intermediate 11 (360 mg, 74%) as a white solid.1H-NMR (CDC13, 300 MHz): delta 9.79 (s, 1H), 7.83 (d, J= 7.8 Hz, 1H), 7.35 (m, 1H), 7.19-7.17 (m, 1H), 3.96 (s, 3H), 7.21 3.35 (s, 3H)LCMS m/z [M+H]+ C9Hi0FNO4S requires: 248.03. Found 248.08
74%	With pyridine; In dichloromethane; at 0 - 20℃;	Example 105 Preparation of Intermediate 107 [0812] [0813] To a mixture intermediate 106 (334 mg, 1.97 mmol) and pyridine (0.41 mL, 4.95 mmol) in 5.5 mL of dichloromethane at 0 C., was added slowly methanesulfonyl chloride (0.40 mL, 4.95 mmol). The mixture was warmed to room temperature and stirred overnight. HPLC indicated 48% conversion to desired product. Pyridine (0.55 mL) and 0.50 mL of methanesulfonyl chloride (approximately 6.8 mmol each) was then added at room temperature. After a total of 40 hours, reaction mixture was quenched with 10 mL of 1N HCl. After 5 minutes of stirring, mixture was poured into 20 mL of water. The aqueous layer was extracted with ethyl acetate (3×30 mL). The combined organic layers were washed with 100 mL of 1N HCl(aq) and 100 mL brine, separated, dried (MgSO4), filtered, and concentrated under reduced pressure. Column chromatography (15-50% ethyl acetate in hexanes) yielded intermediate 107 (360 mg, 74%) as a white solid. [0814] 1H-NMR (CDCl3, 300 MHz): delta 9.79 (s, 1H), 7.83 (d, J=7.8 Hz, 1H), 7.35 (m, 1H), 7.19-7.17 (m, 1H), 3.96 (s, 3H), 7.21-3.35 (s, 3H) [0815] LCMS m/z [M+H]+ C9H10FNO4S requires: 248.03. Found 248.08

References: [1]Patent: WO2011/163518,2011,A1 .Location in patent: Page/Page column 158-159.
[2]Patent: US2013/273037,2013,A1 .Location in patent: Paragraph 0812-0815.
[3]Journal of Medicinal Chemistry,2015,vol. 58,p. 1630 - 1643.

4
[ 144851-82-1 ]
(x)C₂HF₃O₂*C₂₁H₂₄FN₅O₄S [ No CAS ]

References: [1]Patent: WO2011/163518,2011,A1 .

5
[ 144851-82-1 ]
[ 1353628-14-4 ]

References: [1]Patent: WO2011/163518,2011,A1 .
[2]Patent: US2013/273037,2013,A1 .
[3]Journal of Medicinal Chemistry,2015,vol. 58,p. 1630 - 1643.

6
[ 67-56-1 ]
[ 51108-29-3 ]
[ 144851-82-1 ]
[ 1356116-39-6 ]
[ 1356116-41-0 ]

References: [1]Organic Letters,2012,vol. 14,p. 946 - 949.

7
[ 144851-82-1 ]
[ 1470032-29-1 ]

References: [1]Patent: US2013/273037,2013,A1 .

8
[ 144851-82-1 ]
C₂₃H₂₅ClFN₅O₃S*C₂HF₃O₂ [ No CAS ]

References: [1]Patent: US2013/273037,2013,A1 .

9
[ 144851-82-1 ]
[ 77287-34-4 ]
8-fluoroquinazolin-4(3H)-one [ No CAS ]

References: [1]MedChemComm,2014,vol. 5,p. 1290 - 1296.

10
[ 144851-82-1 ]
(S)-N-(2-(2-(5, 6-dimethyl-7-oxo-4,7-dihydropyrazolo[1,5-a]pyrimidin-2-yl)piperidine-1-carbonyl)-6-fluorophenyl)methanesulfonamide trifluoroacetic acid salt [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 1630 - 1643.

11
[ 144851-82-1 ]
[ 906811-49-2 ]

Yield	Reaction Conditions	Operation in experiment
65%	With lithium aluminium tetrahydride; In tetrahydrofuran; at 0℃;	To a suspension of lithium aluminum hydride (1.835 g, 48.3 mmot) in THF (20 mL) was added dropwise at 0 C a solution of <strong>[144851-82-1]methyl 2-amino-3-fluorobenzoate</strong> (90a) (5 g, 32.2 rnmol) in THF (20 inL). The reaction mixture was stirred at room temperature overnight. The mixture was then cooled down to 0 C, quenched with ethyl acetate (30 mL) and water(10 mL). The slurry obtained was filtered through celite and washed with ethyl acetate (50 mL). The aqueous layer was separated and organic layer was dried, filtered and concentrated in vacuum to dryness to give crude product. The crude was purified by flash column chromatography (silica gel 40 g, eluting with 0-100% ethyl acetate in hexane) to furnish (2-Amino-3-fluorophenyl)rnethanol (90b) (2.958 g, 65 % yield) as a tan solid; ?HNMR (300 MHz, DMSO-d) oe 6.98 - 6.86 (in, 2H), 6.52 (td, .1= 7.8, 5.2 Hz, I H), 5.15 0..j= 5.5 Hz, I H), 4.88 (s. 2H), 4.43 (d, J = 5.5 Hz, 2H); ?9F NMR (282 MHz, DMSO-d6) -136.17 (dd,J= 11.3,5.2 Hz); MS (ES+) 165 (M+Na); (ES-) 140.0 (M-l).

References: [1]Patent: WO2015/134998,2015,A1 .Location in patent: Page/Page column 382; 383.

12
[ 144851-82-1 ]
1-(3-cyanophenyl )-N-(2-fluoro-6-(hydroxymethyl)phenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide [ No CAS ]

References: [1]Patent: WO2015/134998,2015,A1 .

13
[ 144851-82-1 ]
1-(3-cyanophenyl)-N-(2-fluoro-6-formylphenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide [ No CAS ]

References: [1]Patent: WO2015/134998,2015,A1 .

14
[ 144851-82-1 ]
1-(3-cyanophenyl)-N-(2-fluoro-6-(hydroxy(phenyl)methyl)phenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide [ No CAS ]

References: [1]Patent: WO2015/134998,2015,A1 .

15
[ 144851-82-1 ]
1-(3-(aminomethyl)phenyl)-N-(2-fluoro-6-(hydroxy(phenyl)methyl)phenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide [ No CAS ]

References: [1]Patent: WO2015/134998,2015,A1 .

16
3-fluoro-2-nitro-benzoic acid [ No CAS ]
[ 144851-82-1 ]

References: [1]Patent: WO2015/184011,2015,A2 .

17
3-fluoro-2-nitro-benzoic acid methyl ester [ No CAS ]
[ 144851-82-1 ]

Yield	Reaction Conditions	Operation in experiment
100%	With palladium 10% on activated carbon; hydrogen; In methanol; water; at 20℃;	[0334] To a stirred solution of 3-fluoro-2-nitro-benzoic acid methyl ester (350 mg, 1.75 rnmol) in MeOH (10 mL) was amed Pd/C (35.0 mg, 10%, wet). The suspension was stirred under H2 at room temperature overnight. The reactant was filtered. The filtrate was evaporated in vacuum to afford 2-arnino3-fluoro-benzoic acid methyl ester (300 mg, yield:100%) as a yellow oil, which was used for next step without further purificaiton.[0335] ?I-I NMR (CDCI3, 300 MHz): 6 7.66 (d, 1H), 7.12 (m, 11-1), 6.58 (t, IH), 5.80 (s, 21-1), 3.90 (s, 3H,).

References: [1]Patent: WO2015/184011,2015,A2 .Location in patent: Paragraph 0333; 0334; 0335.

18
[ 144851-82-1 ]
[ 5535-48-8 ]
8-fluoro-3-(phenylsulfonyl)-2,3-dihydroquinolin-4(1H)-one [ No CAS ]

References: [1]Chemistry Letters,2016,vol. 45,p. 1356 - 1358.

19
[ 144851-82-1 ]
[ 5535-48-8 ]
C₁₆H₁₆FNO₄S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium tert-butylate; bis[2-(diphenylphosphino)phenyl] ether; copper(l) chloride; In toluene; at 22℃; for 20h;Inert atmosphere; Sealed tube;	General procedure: CuCl (1.50 mg, 0.0150 mmol), DPEPhos (8.10 mg, 0.0150 mmol) and KOt-Bu (1.70 mg,0.0150 mmol) were added to a 8 mL vial charged with a magnetic bar. The vial was sealedwith a cap (phenolic open top cap with gray PTFE/silicone) and purged by N2 gas for 5 min.Toluene (0.8 mL) and methyl 2-aminobenzoate (1a) (46.6 L, 0.360 mmol) were added to themixture, which was allowed for 10 min. And then a solution of phenyl vinyl sulfone (2) (50.5mg, 0.300 mmol) in toluene (0.7 mL) was added to the reaction solution. After stirring atroom temperature for 5 h, THF (5 mL) was added and the reaction was allowed to cool to 0C (ice bath). After addition of KOt-Bu (101 mg, 0.900 mmol), the resulting solution wasallowed to stir for further 1 h at 0 C. After that time, the reaction was quenched with asaturated aqueous solution of NH4Cl (1 mL) and NaHCO3 (2 mL) and washed with EtOAc (7x 3 mL). The organic layers were combined, dried over MgSO4, filtered, and concentrated invacuo. The crude product was purified by silica gel column chromatography (CH2Cl2/EtOAc,8:1) to afford the desired product 4a (76.8 mg, 0.267 mmol, 89% yield) as a yellow solid.

References: [1]Chemistry Letters,2016,vol. 45,p. 1356 - 1358.

20
[ 144851-82-1 ]
[ 1413944-33-8 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 711 - 719.

21
[ 420-04-2 ]
[ 144851-82-1 ]
[ 1379218-75-3 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; In ethanol; water; at 100℃;	Into a 500mL round bottom flask equipped with a magnetic stir bar was placed methyl 2-amino-6-methoxybenzoate (25 g, 149.6 mmol), ethanol (200 mL), cyanamide (9.43 g, 224 mmol), and concentrated HCl (6 mL). The mixture was allowed to stir at reflux for 6 hours. At one hour intervals, concentrated HCl (0.5 mL) was added. The reaction mixture was allowed to cool to room temperature and the solid, 7i, was isolated via filtration and washed with ethanol. 1H NMR (400 MHz, DMSO-d6) delta ppm 3.88 (s, 3 H), 6.96 (dd, J=8.2, 3.1 Hz, 2 H), 7.69 (t, J=8.3 Hz, 1 H), 8.28 (br. s., 2 H), 12.67 (br. s., 1 H)
	With hydrogenchloride; In ethanol; water; at 80℃; for 18h;	<strong>[144851-82-1]2-amino-3-fluoro-benzoic acid methyl ester</strong> (15g, 88.68 mmol) was dissolved in EtOH (100 ml_) in a 250ml_ pressure tube, then cyanamide (5.59 g, 133 mmol) and HCI (37% in H2O) were added and the reaction mixture stirred 18h at 80C. Upon cooling, a precipitate formed and isolated by filtration, washed with EtOH and dried in vacuo to afford the title compound as a white powder. Rt: 0.44min., m/z - 180 [M+H], method B.

References: [1]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 711 - 719.
[2]Patent: WO2019/166532,2019,A1 .Location in patent: Page/Page column 27; 28.

22
[ 144851-82-1 ]
[ 1126475-31-7 ]

References: [1]Patent: WO2009/27730,2009,A1 .

23
[ 144851-82-1 ]
[ 1126475-34-0 ]

References: [1]Patent: WO2009/27730,2009,A1 .

24
[ 144851-82-1 ]
[ 1126475-37-3 ]

References: [1]Patent: WO2009/27730,2009,A1 .

25
[ 144851-82-1 ]
1-{3-[(4-ethyl-3-oxopiperazin-1-yl)carbonyl]-4-fluorobenzyl}-8-hydroxy-4-oxo-1,4-dihydrocinnolin-1-ium trifluoroacetate [ No CAS ]

References: [1]Patent: WO2009/27730,2009,A1 .

26
[ 144851-82-1 ]
[ 1126475-32-8 ]

References: [1]Patent: WO2009/27730,2009,A1 .

27
[ 144851-82-1 ]
[ 1126473-84-4 ]

References: [1]Patent: WO2009/27730,2009,A1 .

28
[ 144851-82-1 ]
3-fluoro-2-isobutylamido-N,N-dimethylbenzamide [ No CAS ]