380430-55-7|(2-Amino-4-(methoxycarbonyl)phenyl)boronic acid hydrochloride| Ambeed

Structure of 380430-55-7

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Quality Control of [ 380430-55-7 ] Purity: 97% SDS Specification

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Product Details of [ 380430-55-7 ]

CAS No. :	380430-55-7
Formula :	C₈H₁₁BClNO₄
M.W :	231.44
SMILES Code :	OB(C1=CC=C(C(OC)=O)C=C1N)O.[H]Cl
MDL No. :	MFCD02258941
InChI Key :	IDUSDMZTKZZVAW-UHFFFAOYSA-N
Pubchem ID :	16427083

Safety of [ 380430-55-7 ]

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

Computational Chemistry of [ 380430-55-7 ] Show Less

Physicochemical Properties

Num. heavy atoms	15
Num. arom. heavy atoms	6
Fraction Csp3	0.12
Num. rotatable bonds	3
Num. H-bond acceptors	4.0
Num. H-bond donors	3.0
Molar Refractivity	58.92
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	92.78 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	0.0
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	1.35
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	-0.45
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.	-0.04
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	-1.56
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	-0.14

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.22
Solubility	1.38 mg/ml ; 0.00598 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.	-2.9
Solubility	0.291 mg/ml ; 0.00126 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	-1.01
Solubility	22.6 mg/ml ; 0.0977 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	No
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.	-6.75 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.	0.55

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	2.0 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)	1.87

Application In Synthesis of [ 380430-55-7 ]

* 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 [ 380430-55-7 ]

[ 380430-55-7 ] Synthesis Path-Downstream 1~35

1
[ 1009826-93-0 ]
[ 380430-55-7 ]
methyl 5-oxo-5,6-dihydropyrimido[4,5-c]-quinoline-8-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
8.5%	With sodium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In N,N-dimethyl-formamide; at 120℃; for 18.0h;	Sodium acetate (4.0 eq, 1.92 g, 23.41 mmol) and 1,1'- bis(diphenylphosphino)ferrocene palladium (II) chloride (complexed with dichloromethane) (0.05 eq, 214 mg, 0.29 mmol) were added to a mixture of methyl-5- bromopyrimidine-4-carboxylate (1.0 eq, 1.27 g, 5.85 mmol), and 2-amino-4- (methoxycarbonyl)phenylboronic acid hydrochloride (1.0 eq, 1.35 g, 5.85 mmol) in anydrous DMF (10 ml). The Mixture was stirred under nitrogen atmosphere at 1200C for 18 hours. Water and brine were added and the resulting solid impurities filtered off. The material was extracted with CH2Cl2 (4x) and the combined extracts dried over Na2SO4. After evaporation of CH2Cl2, the remaining DMF was evaporated by heating the residue in vacuo. The resulting solid was triturated in CH2Cl2, filtered and <n="76"/>dried to provide methyl 5-oxo-5,6-dihydropyrimido[4,5-c]quinoline-8-carboxylate as a beige solid (127 mg, 8.5percent yield). LCMS (ES): >80percent pure, m/z 256 [M+l]+; 1H NMR (DMSO-^6, 400 MHz) delta 3.79 (s, 3H), 7.81 (d, / = 8.0, IH), 8.68 (d, / = 8.8, IH), 9.49 (s, IH), 10.19 (s, IH), 12.37 (s, IH) ppm.
8.5%	With sodium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In N,N-dimethyl-formamide; at 120℃; for 18.0h;	Process 5 Sodium acetate (4.0 eq, 1.92 g, 23.41 mmol) and 1,1'-bis(diphenylphosphino)ferrocene palladium (II) chloride (complexed with dichloromethane) (0.05 eq, 214 mg, 0.29 mmol) were added to a mixture of methyl-5-bromopyrimidine-4-carboxylate (1.0 eq, 1.27 g, 5.85 mmol), and <strong>[380430-55-7]2-amino-4-(methoxycarbonyl)phenylboronic acid hydrochloride</strong> (1.0 eq, 1.35 g, 5.85 mmol) in anhydrous DMF (10 ml). The mixture was stirred under nitrogen atmosphere at 120° C. for 18 hours. Water and brine were added and the resulting solid impurities filtered off. The material was extracted with CH2Cl2 (4.x.) and the combined extracts dried over Na2SO4. After evaporation of CH2Cl2, the remaining DMF was evaporated by heating the residue in vacuo. The resulting solid was triturated in CH2Cl2, filtered and dried to provide methyl 5-oxo-5,6-dihydropyrimido[4,5-c]quinoline-8-carboxylate as a beige solid (127 mg, 8.5percent yield). LCMS (ES): >80percent pure, m/z 256 [M+1]+; 1H NMR (DMSO-d6, 400 MHz) delta 3.79 (s, 3H), 7.81 (d, J=8.0, 1H), 8.68 (d, J=8.8, 1H), 9.49 (s, 1H), 10.19 (s, 1H), 12.37 (s, 1H) ppm.
	With sodium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In N,N-dimethyl-formamide; at 120℃; for 18.0h;Inert atmosphere;	Sodium acetate (4.0 eq, 1.92 g, 23.41 mmol) and 1,1'-bis(diphenylphosphino)ferrocene palladium (II) chloride (complexed with dichloromethane) (0.05 eq, 214 mg, 0.29 mmol) were added to a mixture of methyl-5-bromopyrimidine-4-carboxylate (1.0 eq, 1.27 g, 5.85 mmol), and <strong>[380430-55-7]2-amino-4-(methoxycarbonyl)phenylboronic acid hydrochloride</strong> (1.0 eq, 1.35 g, 5.85 mmol) in anhydrous DMF (10 ml). The Mixture was stirred under nitrogen atmosphere at 120° C. for 18 hours. Water and brine were added and the resulting solid impurities filtered off. The material was extracted with CH2Cl2 (4.x.) and the combined extracts dried over Na2SO4. After evaporation of CH2Cl2, the remaining DMF was evaporated by heating the residue in vacuo. The resulting solid was triturated in CH2Cl2, filtered and dried to provide methyl 5-oxo-5,6-dihydropyrimido[4,5-c]quinoline-8-carboxylate as a beige solid (127 mg, 8.5percent yield). LCMS (ES): >80percent pure, m/z 256 [M+1]+; 1H NMR (DMSO-d6, 400 MHz) delta 3.79 (s, 3H), 7.81 (d, J=8.0, 1H), 8.68 (d, J=8.8, 1H), 9.49 (s, 1H), 10.19 (s, 1H), 12.37 (s, 1H) ppm.

References: [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 635 - 654.
[2]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 1687 - 1691.
[3]Patent: WO2008/28168,2008,A2 .Location in patent: Page/Page column 74-75.
[4]Patent: US2009/93465,2009,A1 .Location in patent: Page/Page column 32.
[5]Patent: US2009/239859,2009,A1 .Location in patent: Page/Page column 41-42.

2
[ 1009827-04-6 ]
[ 380430-55-7 ]
methyl 3-(methylamino)-5-oxo-5,6-dihydropyrimido[4,5-c]quinoline-8-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
21%	With sodium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In N,N-dimethyl-formamide; at 120℃; for 0.166667h;Microwave;	Sodium acetate (3.0 eq, 240 mg, 2.93 mmol) and 1,1'- bis(diphenylphosphino)ferrocene palladium (II) chloride (complexed with dichloromethane) (0.05 eq, 36 mg, 0.049 mmol) were added to a mixture of methyl 5- bromo-2-(methylamino)pyrimidine-4-carboxylate (1.0 eq, 240 mg, 0.975mmol), and <strong>[380430-55-7]2-amino-4-(methoxycarbonyl)phenylboronic acid hydrochloride</strong> (1.0 eq, 226 mg, 0.98 mmol) in anydrous DMF (2 ml). The mixture was stirred under microwave heating at 1200C for 10 min. Addition of water induced precipitation of the expected compound that was filtered and dried, methyl 3-(methylamino)-5-oxo-5,6-dihydropyrimido[4,5- c]quinoline-8-carboxylate (57 mg, 21percent yield). LCMS (ES): >80percent pure, m/z 285 [M+l]+.
	With sodium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In N,N-dimethyl-formamide; at 120℃; for 18.0h;	Sodium acetate (3.0 eq, 240 mg, 2.93 mmol) and 1,1'-bis(diphenylphosphino)ferrocene palladium (II) chloride (complexed with dichloromethane) (0.05 eq, 36 mg, 0.049 mmol) were added to a mixture of methyl 5-bromo-2-(methylamino)pyrimidine-4-carboxylate (1.0 eq, 240 mg, 0.975 mmol), and <strong>[380430-55-7]2-amino-4-(methoxycarbonyl)phenylboronic acid hydrochloride</strong> (1.0 eq, 226 mg, 0.98 mmol) in anhydrous DMF (2 ml). The mixture was stirred under microwave heating at 120° C. for 10 min. Addition of water induced precipitation of the expected compound that was filtered and dried. methyl 3-(methylamino)-5-oxo-5,6-dihydropyrimido[4,5-c]quinoline-8-carboxylate (57 mg, 21percent yield). LCMS (ES): >80percent pure, m/z 285 [M+1]+.

References: [1]Patent: WO2008/28168,2008,A2 .Location in patent: Page/Page column 79.
[2]Patent: US2009/239859,2009,A1 .Location in patent: Page/Page column 44-45.

3
[ 380430-55-7 ]
[ 50593-91-4 ]
methyl 3-(methylthio)-5-oxo-5,6-dihydropyrimido[4,5-c]quinoline-8-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
10%	With sodium acetate; In N,N-dimethyl-formamide; at 120℃; for 0.666667h;Microwave;	In a microwave vessel, methyl 5-bromo-2-(methylthio)pyrimidine-4- carboxylate (1.0 eq, 274 mg, 1.18 mmol), <strong>[380430-55-7]2-amino-4-(methoxycarbonyl)phenylboronic acid hydrochloride</strong> (1.2 eq, 329 mg, 1.42 mmol), and sodium acetate (3.0 eq, 291 mg, 3.55 mmol) were mixed in anhydrous DMF (2 ml). The mixture was degassed by bubbling nitrogen gas in the solution for 10 min and the reaction heated under microwaves at 1200C for 30 min. After cooling down the expected material crashed out of NMP. The solid was filtered, suspended in water filtered and dried. The material was triturated in AcOEt and filtered give a yellow solid. The same procedure was repeated 9 times using the same amounts of materials to provide methyl 3-(methylthio)-5-oxo-5,6-dihydropyrimido[4,5-c]quinoline-8- carboxylate (283 mg, 10% yield). LCMS (ES): >95% pure, m/z 302 [M+l]+, 1H NMR <n="82"/>(DMSO-d6, 400 MHz) delta 2.71 (s, 3H), 3.89 (s, 3H), 7.80 (dd, / = 1.6, / = 8.4, IH), 7.97 (d, / = 1.6, IH), 8.59 (d, / = 8.8, IH), 9.98 (s, IH), 12.34 (s, IH) ppm.
10%	With sodium acetate; In N,N-dimethyl-formamide; at 120℃; for 0.666667h;Microwave irradiation;	Process 8 In a microwave vessel, methyl 5-bromo-2-(methylthio)pyrimidine-4-carboxylate (1.0 eq, 274 mg, 1.18 mmol), <strong>[380430-55-7]2-amino-4-(methoxycarbonyl)phenylboronic acid hydrochloride</strong> (1.2 eq, 329 mg, 1.42 mmol), and sodium acetate (3.0 eq, 291 mg, 3.55 mmol) were mixed in anhydrous DMF (2 ml). The mixture was degassed by bubbling nitrogen gas in the solution for 10 min and the reaction heated under microwaves at 120 C. for 30 min. After cooling down the expected material crashed out of NMP. The solid was filtered, suspended in water filtered and dried. The material was triturated in AcOEt and filtered give a yellow solid. The same procedure was repeated 9 times using the same amounts of materials to provide methyl 3-(methylthio)-5-oxo-5,6-dihydropyrimido[4,5-c]quinoline-8-carboxylate (283 mg, 10% yield). LCMS (ES): >95% pure, m/z 302 [M+l]+, 1H NMR (DMSO-d6, 400 MHz) delta 2.71 (s, 3H), 3.89 (s, 3H), 7.80 (dd, J=1.6, J=8.4, 1H), 7.97 (d, J=1.6, 1H), 8.59 (d, J=8.8, 1H), 9.98 (s, 1H), 12.34 (s, 1H) ppm.
10%	With sodium acetate; In N,N-dimethyl-formamide; at 120℃; for 0.666667h;Microwave irradiation;	In a microwave vessel, methyl 5-bromo-2-(methylthio)pyrimidine-4-carboxylate (1.0 eq, 274 mg, 1.18 mmol), <strong>[380430-55-7]2-amino-4-(methoxycarbonyl)phenylboronic acid hydrochloride</strong> (1.2 eq, 329 mg, 1.42 mmol), and sodium acetate (3.0 eq, 291 mg, 3.55 mmol) were mixed in anhydrous DMF (2 ml). The mixture was degassed by bubbling nitrogen gas in the solution for 10 min and the reaction heated under microwaves at 120 C. for 30 min. After cooling down the expected material crashed out of NMP. The solid was filtered, suspended in water filtered and dried. The material was triturated in AcOEt and filtered give a yellow solid. The same procedure was repeated 9 times using the same amounts of materials to provide methyl 3-(methylthio)-5-oxo-5,6-dihydropyrimido[4,5-c]quinoline-8-carboxylate (283 mg, 10% yield). LCMS (ES): >95% pure, m/z 302 [M+1]+, 1H NMR (DMSO-d6, 400 MHz) delta 2.71 (s, 3H), 3.89 (s, 3H), 7.80 (dd, J=1.6, J=8.4, 1H), 7.97 (d, J=1.6, 1H), 8.59 (d, J=8.8, 1H), 9.98 (s, 1H), 12.34 (s, 1H) ppm.

References: [1]Patent: WO2008/28168,2008,A2 .Location in patent: Page/Page column 80-81.
[2]Patent: US2009/93465,2009,A1 .Location in patent: Page/Page column 33.
[3]Patent: US2009/239859,2009,A1 .Location in patent: Page/Page column 45.

4
[ 76360-43-5 ]
[ 380430-55-7 ]
[ 1009827-21-7 ]

Yield	Reaction Conditions	Operation in experiment
50%	With sodium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In N,N-dimethyl-formamide; at 120℃; for 0.166667h;Microwave;	In a microwave vessel, methyl 2-bromo-3-thiophene carboxylate (1.0 eq, 260 mg, 1.18 mmol), <strong>[380430-55-7]2-amino-4-(methoxycarbonyl)phenylboronic acid hydrochloride</strong> (1.1 eq, 300 mg, 1.30 mmol), sodium acetate (3.0 eq, 292 mg, 3.56 mmol) and PdCl2(dppf) (0.05 eq, 31 mg, 0.059 mmol) were mixed together in anhydrous DMF (2 ml). The mixture was heated in a microwave oven at 1200C for 10 mn. Water was added and the solid filtered and dried. The material was suspended in CH2Cl2 , filtered and dried to afford methyl 4-oxo-4,5-dihydrothieno[3,2-c]quinoline-7-carboxylate as a yellow solid (152 mg, 50percent yield). LCMS (ES): 95percent pure, m/z 260 [M+l]+ ; <n="104"/>1H NMR (CDCl3, 400 MHz) delta 3. 99 (s, 3H), 7.54 (d, / = 5.2, IH), 7.79 (d, / = 4.8, IH), 7.86 (d, J = 8.4, IH), 7.91 (dd, J = 8.4, / = 1.6, IH), 8.03 (d, J = 1.2, IH) ppm.
50%	With sodium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In N,N-dimethyl-formamide; at 120℃; for 0.166667h;Microwave irradiation;	Process 11 In a microwave vessel, methyl 2-bromo-3-thiophene carboxylate (1.0 eq, 260 mg, 1.18 mmol), <strong>[380430-55-7]2-amino-4-(methoxycarbonyl)phenylboronic acid hydrochloride</strong> (1.1 eq, 300 mg, 1.30 mmol), sodium acetate (3.0 eq, 292 mg, 3.56 mmol) and PdCl2(dppf) (0.05 eq, 31 mg, 0.059 mmol) were mixed together in anhydrous DMF (2 ml). The mixture was heated in a microwave oven at 120° C. for 10 nm. Water was added and the solid filtered and dried. The material was suspended in CH2Cl2, filtered and dried to afford methyl 4-oxo-4,5-dihydrothieno[3,2-c]quinoline-7-carboxylate as a yellow solid (152 mg, 50percent yield). LCMS (ES): 95percent pure, m/z 260 [M+1]+; 1H NMR (CDCl3, 400 MHz) delta 3.99 (s, 3H), 7.54 (d, J=5.2, 1H), 7.79 (d, J=4.8, 1H), 7.86 (d, J=8.4, 1H), 7.91 (dd, J=8.4, J=1.6, 1H), 8.03 (d, J=1.2, 1H) ppm.
50%	With sodium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In N,N-dimethyl-formamide; at 120℃; for 0.166667h;Microwave irradiation;	In a microwave vessel, methyl 2-bromo-3-thiophene carboxylate (1.0 eq, 260 mg, 1.18 mmol), <strong>[380430-55-7]2-amino-4-(methoxycarbonyl)phenylboronic acid hydrochloride</strong> (1.1 eq, 300 mg, 1.30 mmol), sodium acetate (3.0 eq, 292 mg, 3.56 mmol) and PdCl2(dppf) (0.05 eq, 31 mg, 0.059 mmol) were mixed together in anhydrous DMF (2 ml). The mixture was heated in a microwave oven at 120° C. for 10 nm. Water was added and the solid filtered and dried. The material was suspended in CH2Cl2, filtered and dried to afford methyl 4-oxo-4,5-dihydrothieno[3,2-c]quinoline-7-carboxylate as a yellow solid (152 mg, 50percent yield). LCMS (ES): 95percent pure, m/z 260 [M+1]+; 1H NMR (CDCl3, 400 MHz) delta 3.99 (s, 3H), 7.54 (d, J=5.2, 1H), 7.79 (d, J=4.8, 1H), 7.86 (d, J=8.4, 1H), 7.91 (dd, J=8.4, J=1.6, 1H), 8.03 (d, J=1.2, 1H) ppm.

References: [1]Patent: WO2008/28168,2008,A2 .Location in patent: Page/Page column 102-103.
[2]Patent: US2009/93465,2009,A1 .Location in patent: Page/Page column 46.
[3]Patent: US2009/239859,2009,A1 .Location in patent: Page/Page column 90-91.
[4]Journal of Medicinal Chemistry,2011,vol. 54,p. 635 - 654.

5
[ 913836-22-3 ]
[ 380430-55-7 ]
[ 1009827-48-8 ]

Yield	Reaction Conditions	Operation in experiment
39%	With sodium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In N,N-dimethyl-formamide; at 120℃; for 0.166667h;Microwave;	In a microwave vessel, methyl 5-bromothiazole-4-carboxylate (1.0 eq, 97 mg, 0.44 mmol), 2-amino-3-methoxycarbonyl phenyl boronic acid HCl (1.1 eq, 111 mg, 0.48 mmol), sodium acetate (3.0 eq, 107 mg, 1.31 mmol) and PdCl2(dppf) (0.05 eq, 11 mg, 0.022 mmol) were mixed together in anhydrous DMF (1 ml). The mixture was heated in a microwave oven at 1200C for 10 mn. Water was added and the material extracted with CH2CI2. The combined extracts wre washed with brine, dried over Na2SO4 and the solvents removed by evaporation. The material was dissolved in <n="159"/>a mixture of CH2CI2 and MeOH and the solution filtered through a pad of celite. Evaporation of the volatiles afforded crude methyl 4-oxo-4,5-dihydrothiazolo[4,5- c]quinoline-7-carboxylate as a black solid (44 mg, 39percent yield). A small part of the compound was subjected to preparative HPLC for analytical purpose. LCMS (ES): 95percent pure, m/z 261 [M+l]+.
39%	With sodium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In N,N-dimethyl-formamide; at 120℃; for 0.166667h;Microwave irradiation;	Process 24 In a microwave vessel, methyl 5-bromothiazole-4-carboxylate (1.0 eq, 97 mg, 0.44 mmol), 2-amino-3-methoxycarbonyl phenyl boronic acid HCl (1.1 eq, 111 mg, 0.48 mmol), sodium acetate (3.0 eq, 107 mg, 1.31 mmol) and PdCl2(dppf) (0.05 eq, 11 mg, 0.022 mmol) were mixed together in anhydrous DMF (1 ml). The mixture was heated in a microwave oven at 120° C. for 10 nm. Water was added and the material extracted with CH2Cl2. The combined extracts were washed with brine, dried over Na2SO4 and the solvents removed by evaporation. The material was dissolved in a mixture of CH2Cl2 and MeOH and the solution filtered through a pad of celite. Evaporation of the volatiles afforded crude methyl 4-oxo-4,5-dihydrothiazolo[4,5-c]quinoline-7-carboxylate as a black solid (44 mg, 39percent yield). A small part of the compound was subjected to preparative HPLC for analytical purpose. LCMS (ES): 95percent pure, m/z 261 [M+1]+.
	With sodium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In N,N-dimethyl-formamide; at 120℃; for 0.166667h;Microwave irradiation;	In a microwave vessel, methyl 5-bromothiazole-4-carboxylate (1.0 eq, 97 mg, 0.44 mmol), 2-amino-3-methoxycarbonyl phenyl boronic acid HCl (1.1 eq, 111 mg, 0.48 mmol), sodium acetate (3.0 eq, 107 mg, 1.31 mmol) and PdCl2(dppf) (0.05 eq, 11 mg, 0.022 mmol) were mixed together in anhydrous DMF (1 ml). The mixture was heated in a microwave oven at 120° C. for 10 nm. Water was added and the material extracted with CH2Cl2. The combined extracts were washed with brine, dried over Na2SO4 and the solvents removed by evaporation. The material was dissolved in a mixture of CH2Cl2 and MeOH and the solution filtered through a pad of celite. Evaporation of the volatiles afforded crude methyl 4-oxo-4,5-dihydrothiazolo[4,5-c]quinoline-7-carboxylate as a black solid (44 mg, 39percent yield). A small part of the compound was subjected to preparative HPLC for analytical purpose. LCMS (ES): 95percent pure, m/z 261 [M+1]+.

References: [1]Patent: WO2008/28168,2008,A2 .Location in patent: Page/Page column 157-158.
[2]Patent: US2009/93465,2009,A1 .Location in patent: Page/Page column 50.
[3]Patent: US2009/239859,2009,A1 .Location in patent: Page/Page column 138.

6
[ 380430-55-7 ]
[ 63592-85-8 ]
[ 1186040-13-0 ]

Yield	Reaction Conditions	Operation in experiment
90%	With caesium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; water; for 0.666667h;Reflux;	A solution of methyl 4-chloronicotinate (1.68 g, 6.05 mmol), <strong>[380430-55-7]2-amino-4-(methoxycarbonyl)phenylboronic acid hydrochloride</strong> (3.17 g, 13.70 mmol), Cs2CO3 (8.90 g, 27.32 mmol), and PdCl2(dppf) (335 mg, 0.46 mmol) in dioxane (5percent H2O, 60 mL) was heated at reflux for 40 min. The reaction was cooled to rt, the precipitate was collected by filtration, and washed (dioxane, H2O, then with MeOH) to yield the desired lactam (2.07 g, 90percent). LCMS (ES): >95percent pure, m/z 255 [M+1]+.

References: [1]Patent: US2009/239859,2009,A1 .Location in patent: Page/Page column 305.

7
[ 380430-55-7 ]
[ 24424-99-5 ]
[ 1186638-14-1 ]