[ CAS No. 1427587-32-3 ] {[proInfo.proName]}

Name: 1427587-32-3|1-Methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroquinolin-2(1H)-one|95%
Brand: Ambeed
SKU: A234517
Rating: 92 (32 reviews)

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Cat. No.: {[proInfo.prAm]}

2D 3D

Structure of 1427587-32-3 * Storage: {[proInfo.prStorage]}

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Quality Control of [ 1427587-32-3 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 1427587-32-3 ]

SDS Specification

Alternatived Products of [ 1427587-32-3 ]

Product Details of [ 1427587-32-3 ]

CAS No. :	1427587-32-3	MDL No. :	MFCD23106122
Formula :	C₁₆H₂₂BNO₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	KBKLZANEYMGZGD-UHFFFAOYSA-N
M.W :	287.16	Pubchem ID :	72208233
Synonyms :

Calculated chemistry of [ 1427587-32-3 ]

Physicochemical Properties

Num. heavy atoms :	21
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.56
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	0.0
Molar Refractivity :	87.92
TPSA :	38.77 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	Yes
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	Yes
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.46 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	2.24
Log Po/w (WLOGP) :	1.51
Log Po/w (MLOGP) :	1.64
Log Po/w (SILICOS-IT) :	1.91
Consensus Log Po/w :	1.46

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	0.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-3.18
Solubility :	0.191 mg/ml ; 0.000665 mol/l
Class :	Soluble
Log S (Ali) :	-2.69
Solubility :	0.587 mg/ml ; 0.00204 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-4.43
Solubility :	0.0106 mg/ml ; 0.0000369 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	0.0
Synthetic accessibility :	2.87

Safety of [ 1427587-32-3 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 1427587-32-3 ]

* 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.

Upstream synthesis route of [ 1427587-32-3 ]
Downstream synthetic route of [ 1427587-32-3 ]

[ 1427587-32-3 ] Synthesis Path-Upstream 1~3

1
[ 1092523-03-9 ]
[ 73183-34-3 ]
[ 1427587-32-3 ]

Yield	Reaction Conditions	Operation in experiment
73%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium acetate In 1,4-dioxane at 80℃; Inert atmosphere	A flask was charged with 6-bromo-1-methyl-3,4-dihydro-1H-quinolin-2-one (3 g, 12.5 mmol), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (3.81 g, 15.0 mmol), potassium acetate (3.68 g, 37.5 mmol) and dioxane (48 mL). The mixture was purged with Ar, then dichloro[1,1′-bis(diphenylphosphino)-ferrocene]palladium(II) dichloromethane complex (1:1) [PdCl₂(DPPF)-CH₂Cl₂adduct] (457 mg, 0.625 mmol) was added and the resulting mixture was heated to 80° C. over night. The reaction mixture was diluted with EtOAc, filtered through Dicalite and washed with EtOAc (2×150 mL). The resulting filtrate was washed with brine, dried over Na₂SO₄, filtered and evaporated to dryness. The residue was purified by silica gel flash chromatography eluting with a 0 to 40percent EtOAc-heptane gradient to give the title compound (2.63 g, 73percent) as an off white solid. MS: 288.0 (M+H⁺)
73%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium carbonate In 1,4-dioxane at 80℃; Inert atmosphere	[B] l-Methyl-6-(4,4,5.5-tetramethyl-[l,3,21dioxaborolan-2-yl -3.4-dihvdro-lH-quinolin-2- one A flask was charged with 6-bromo-l-methyl-3,4-dihydro-lH-quinolin-2-one (3 g, 12.5 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-?z^'(l,3,2-dioxaborolane) (3.81 g, 15.0 mmol), potassium acetate (3.68 g, 37.5 mmol) and dioxane (48 mL). The mixture was purged with Ar, then dichloro [1,1 '-?z5(diphenylphosphino)-ferrocene]palladium(II) dichloromethane complex (1 : 1) [PdCl₂(DPPF)-CH₂Cl₂ adduct] (457 mg, 0.625 mmol) was added and the resulting mixture was heated to 80 °C over night. The reaction mixture was diluted with EtOAc, filtered through Dicalite and washed with EtOAc (2 x 150 mL). The resulting filtrate was washed with brine, dried over Na₂S0₄, filtered and evaporated to dryness. The residue was purified by silica gel flash chromatography eluting with a 0 to 40percent EtO Ac- heptane gradient to give the title compound (2.63 g, 73 percent) as an off white solid. MS: 288.0 (M+H⁺).
73%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium acetate In 1,4-dioxane at 80℃; Inert atmosphere	[B] l-Methyl-6-(4,4,5.5-tetramethyl-[l,3,21dioxaborolan-2-yl -3.4-dihvdro-lH-quinolin-2- oneA flask was charged with 6-bromo-l-methyl-3,4-dihydro-lH-quinolin-2-one (3 g, 12.5 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-¾z^'(l,3,2-dioxaborolane) (3.81 g, 15.0 mmol), potassium acetate (3.68 g, 37.5 mmol) and dioxane (48 mL). The mixture was purged with Ar, then dichloro[l, -¾z5(diphenylphosphino)-ferrocene]palladium(II) dichloromethane complex (1 : 1) [PdCl₂(DPPF)-CH₂Cl₂ adduct] (457 mg, 0.625 mmol) was added and the resulting mixture was heated to 80 °C over night. The reaction mixture was diluted with EtOAc, filtered through Dicalite and washed with EtOAc (2 x 150 mL). The resulting filtrate was washed with brine, dried over Na₂S0₄, filtered and evaporated to dryness. The residue was purified by silica gel flash chromatography eluting with a 0 to 40percent EtO Ac- heptane gradient to give the title compound (2.63 g, 73 percent) as an off white solid. MS: 288.0 (M+H⁺).

73%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium acetate In 1,4-dioxane at 80℃; Inert atmosphere	A flask was charged with 6-bromo-l-methyl-3,4-dihydro-lH-quinolin-2-one (3 g, 12.5 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi^'(l,3,2-dioxaborolane) (3.81 g, 15.0 mmol), potassium acetate (3.68 g, 37.5 mmol) and dioxane (48 mL). The mixture was purged with Ar, then dichloro[l,l'- bi5^,(diphenylphosphino)-ferrocene]palladium(II) dichloromethane complex (1 : 1) [PdCl₂(DPPF)- CH₂C1₂ adduct] (457 mg, 0.625 mmol) was added and the resulting mixture was heated to 80 °C over night. The reaction mixture was diluted with EtOAc, filtered through Dicalite and washed with EtOAc (2 x 150 mL). The resulting filtrate was washed with brine, dried over Na₂S0₄, filtered and evaporated to dryness. The residue was purified by silica gel flash chromatography eluting with a 0 to 40percent EtO Ac-heptane gradient to give the title compound (2.63 g, 73 percent) as an off white solid. MS: 288.0 (M+H⁺).
73%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium acetate In 1,4-dioxane at 80℃; Inert atmosphere	ΓΒ1 l-Methyl-6-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-3,4-dihvdroquinolin-2-one A flask was charged with 6-bromo-l-methyl-3,4-dihydroquinolin-2-one (3 g, 12.5 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-b (l,3,2-dioxaborolane) (3.81 g, 15.0 mmol), potassium acetate (3.68 g, 37.5 mmol) and dioxane (48 mL). The mixture was purged with Ar, then dichloro[l, -b 5'(diphenylphosphino)-ferrocene]palladium(II) dichloromethane complex (1: 1) [PdCl₂(DPPF) dichloromethane adduct] (457 mg, 0.560 mmol) was added and the resulting mixture was heated to 80 °C overnight. The reaction mixture was diluted with EtOAc, filtered through Celite and washed with EtOAc (2 x 150 mL). The resulting filtrate was washed with brine, dried over anhy. Na₂S0₄, filtered and evaporated to dryness. The residue was purified by silica gel flash chromatography eluting with a 0 to 40percent EtO Ac- heptane gradient to give the title compound (2.63 g, 73 percent) as an off white solid. MS: 288.0 (M+H⁺).
73%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium acetate In 1,4-dioxane at 80℃; Inert atmosphere	A flask was charged with 6-bromo-l-methyl-3,4-dihydroquinolin-2-one (3 g, 12.5 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-b (l,3,2-dioxaborolane) (3.81 g, 15.0 mmol), potassium acetate (3.68 g, 37.5 mmol) and dioxane (48 mL). The mixture was purged with Ar, then dichloro[l, -b 5'(diphenylphosphino)-ferrocene]palladium(II) dichloromethane complex (1: 1) [PdCl₂(DPPF) dichloromethane adduct] (457 mg, 0.560 mmol) was added and the resulting mixture was heated to 80 °C overnight. The reaction mixture was diluted with EtOAc, filtered through Celite and washed with EtOAc (2 x 150 mL). The resulting filtrate was washed with brine, dried over anhy. Na₂S0₄, filtered and evaporated to dryness. The residue was purified by silica gel flash chromatography eluting with a 0 to 40percent EtOAc - heptane gradient to give the title compound (2.63 g, 73 percent) as an off white solid. MS: 288.0 (M+H⁺).

Reference： [1] Patent: US2013/72679, 2013, A1, . Location in patent: Paragraph 0545; 0546
[2] Patent: WO2013/37779, 2013, A1, . Location in patent: Page/Page column 74; 75
[3] Patent: WO2013/41591, 2013, A1, . Location in patent: Page/Page column 65
[4] Patent: WO2014/139981, 2014, A1, . Location in patent: Page/Page column 24; 25
[5] Patent: WO2016/66662, 2016, A1, . Location in patent: Page/Page column 31
[6] Patent: WO2016/66597, 2016, A1, . Location in patent: Page/Page column 37; 38
[7] Patent: US2016/9720, 2016, A1, . Location in patent: Paragraph 0603
[8] Patent: US2016/9712, 2016, A1, . Location in patent: Paragraph 0373

2
[ 742100-16-9 ]
[ 73183-34-3 ]
[ 1427587-32-3 ]

Yield	Reaction Conditions	Operation in experiment
73%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium acetate In 1,4-dioxane at 80℃; Inert atmosphere	[B] 1-Methyl-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,4-dihydro-1H-quinolin-2-one[0342]6-bromo-1-methyl-3,4-dihydro-1H-quinolin-2-one (3 g, 12.5 mmol), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (3.81 g, 15.0 mmol), potassium acetate (3.68 g, 37.5 mmol) and dioxane (48 mL). The mixture was purged with Ar, then dichloro[1,1′-bis(diphenylphosphino)-ferrocene]palladium(II) dichloromethane complex (1:1) [PdCl₂(DPPF)-CH₂Cl₂adduct] (457 mg, 0.625 mmol) was added and the resulting mixture was heated to 80° C. over night. The reaction mixture was diluted with EtOAc, filtered through Dicalite and washed with EtOAc (2×150 mL). The resulting filtrate was washed with brine, dried over Na₂SO₄, filtered and evaporated to dryness. The residue was purified by silica gel flash chromatography eluting with a 0 to 40percent EtOAc-heptane gradient to give the title compound (2.63 g, 73percent) as an off white solid. MS: 288.0 (M+H⁺).

Reference： [1] Patent: US2013/79365, 2013, A1, . Location in patent: Paragraph 0342; 0343

3
[ 3279-90-1 ]
[ 1427587-32-3 ]

Reference： [1] Patent: WO2013/37779, 2013, A1,
[2] Patent: WO2013/41591, 2013, A1,
[3] Patent: WO2014/139981, 2014, A1,
[4] Patent: US2016/9712, 2016, A1,
[5] Patent: WO2016/66662, 2016, A1,
[6] Patent: WO2016/66597, 2016, A1,
[7] Patent: US2013/72679, 2013, A1,
[8] Patent: US2013/79365, 2013, A1,

[ 1427587-32-3 ] Synthesis Path-Downstream 1~65

1
[ 1092523-03-9 ]
[ 73183-34-3 ]
[ 1427587-32-3 ]

Yield	Reaction Conditions	Operation in experiment
73%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 80.0℃;Inert atmosphere;	A flask was charged with 6-bromo-1-methyl-3,4-dihydro-1H-quinolin-2-one (3 g, 12.5 mmol), 4,4,4?,4?,5,5,5?,5?-octamethyl-2,2?-bi(1,3,2-dioxaborolane) (3.81 g, 15.0 mmol), potassium acetate (3.68 g, 37.5 mmol) and dioxane (48 mL). The mixture was purged with Ar, then dichloro[1,1?-bis(diphenylphosphino)-ferrocene]palladium(II) dichloromethane complex (1:1) [PdCl2(DPPF)-CH2Cl2 adduct] (457 mg, 0.625 mmol) was added and the resulting mixture was heated to 80 C. over night. The reaction mixture was diluted with EtOAc, filtered through Dicalite and washed with EtOAc (2×150 mL). The resulting filtrate was washed with brine, dried over Na2SO4, filtered and evaporated to dryness. The residue was purified by silica gel flash chromatography eluting with a 0 to 40% EtOAc-heptane gradient to give the title compound (2.63 g, 73%) as an off white solid. MS: 288.0 (M+H+)
73%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,4-dioxane; at 80.0℃;Inert atmosphere;	[B] l-Methyl-6-(4,4,5.5-tetramethyl-[l,3,21dioxaborolan-2-yl -3.4-dihvdro-lH-quinolin-2- one A flask was charged with 6-bromo-l-methyl-3,4-dihydro-lH-quinolin-2-one (3 g, 12.5 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-?z'(l,3,2-dioxaborolane) (3.81 g, 15.0 mmol), potassium acetate (3.68 g, 37.5 mmol) and dioxane (48 mL). The mixture was purged with Ar, then dichloro [1,1 '-?z5(diphenylphosphino)-ferrocene]palladium(II) dichloromethane complex (1 : 1) [PdCl2(DPPF)-CH2Cl2 adduct] (457 mg, 0.625 mmol) was added and the resulting mixture was heated to 80 C over night. The reaction mixture was diluted with EtOAc, filtered through Dicalite and washed with EtOAc (2 x 150 mL). The resulting filtrate was washed with brine, dried over Na2S04, filtered and evaporated to dryness. The residue was purified by silica gel flash chromatography eluting with a 0 to 40% EtO Ac- heptane gradient to give the title compound (2.63 g, 73 %) as an off white solid. MS: 288.0 (M+H+).
73%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 80.0℃;Inert atmosphere;	[B] l-Methyl-6-(4,4,5.5-tetramethyl-[l,3,21dioxaborolan-2-yl -3.4-dihvdro-lH-quinolin-2- oneA flask was charged with 6-bromo-l-methyl-3,4-dihydro-lH-quinolin-2-one (3 g, 12.5 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-¾z'(l,3,2-dioxaborolane) (3.81 g, 15.0 mmol), potassium acetate (3.68 g, 37.5 mmol) and dioxane (48 mL). The mixture was purged with Ar, then dichloro[l, -¾z5(diphenylphosphino)-ferrocene]palladium(II) dichloromethane complex (1 : 1) [PdCl2(DPPF)-CH2Cl2 adduct] (457 mg, 0.625 mmol) was added and the resulting mixture was heated to 80 C over night. The reaction mixture was diluted with EtOAc, filtered through Dicalite and washed with EtOAc (2 x 150 mL). The resulting filtrate was washed with brine, dried over Na2S04, filtered and evaporated to dryness. The residue was purified by silica gel flash chromatography eluting with a 0 to 40% EtO Ac- heptane gradient to give the title compound (2.63 g, 73 %) as an off white solid. MS: 288.0 (M+H+).

73%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 80.0℃;Inert atmosphere;	A flask was charged with 6-bromo-l-methyl-3,4-dihydro-lH-quinolin-2-one (3 g, 12.5 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi'(l,3,2-dioxaborolane) (3.81 g, 15.0 mmol), potassium acetate (3.68 g, 37.5 mmol) and dioxane (48 mL). The mixture was purged with Ar, then dichloro[l,l'- bi5,(diphenylphosphino)-ferrocene]palladium(II) dichloromethane complex (1 : 1) [PdCl2(DPPF)- CH2C12 adduct] (457 mg, 0.625 mmol) was added and the resulting mixture was heated to 80 C over night. The reaction mixture was diluted with EtOAc, filtered through Dicalite and washed with EtOAc (2 x 150 mL). The resulting filtrate was washed with brine, dried over Na2S04, filtered and evaporated to dryness. The residue was purified by silica gel flash chromatography eluting with a 0 to 40% EtO Ac-heptane gradient to give the title compound (2.63 g, 73 %) as an off white solid. MS: 288.0 (M+H+).
73%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 80.0℃;Inert atmosphere;	GammaBeta1 l-Methyl-6-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-3,4-dihvdroquinolin-2-one A flask was charged with 6-bromo-l-methyl-3,4-dihydroquinolin-2-one (3 g, 12.5 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-b (l,3,2-dioxaborolane) (3.81 g, 15.0 mmol), potassium acetate (3.68 g, 37.5 mmol) and dioxane (48 mL). The mixture was purged with Ar, then dichloro[l, -b 5'(diphenylphosphino)-ferrocene]palladium(II) dichloromethane complex (1: 1) [PdCl2(DPPF) dichloromethane adduct] (457 mg, 0.560 mmol) was added and the resulting mixture was heated to 80 C overnight. The reaction mixture was diluted with EtOAc, filtered through Celite and washed with EtOAc (2 x 150 mL). The resulting filtrate was washed with brine, dried over anhy. Na2S04, filtered and evaporated to dryness. The residue was purified by silica gel flash chromatography eluting with a 0 to 40% EtO Ac- heptane gradient to give the title compound (2.63 g, 73 %) as an off white solid. MS: 288.0 (M+H+).
73%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 80.0℃;Inert atmosphere;	A flask was charged with 6-bromo-l-methyl-3,4-dihydroquinolin-2-one (3 g, 12.5 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-b (l,3,2-dioxaborolane) (3.81 g, 15.0 mmol), potassium acetate (3.68 g, 37.5 mmol) and dioxane (48 mL). The mixture was purged with Ar, then dichloro[l, -b 5'(diphenylphosphino)-ferrocene]palladium(II) dichloromethane complex (1: 1) [PdCl2(DPPF) dichloromethane adduct] (457 mg, 0.560 mmol) was added and the resulting mixture was heated to 80 C overnight. The reaction mixture was diluted with EtOAc, filtered through Celite and washed with EtOAc (2 x 150 mL). The resulting filtrate was washed with brine, dried over anhy. Na2S04, filtered and evaporated to dryness. The residue was purified by silica gel flash chromatography eluting with a 0 to 40% EtOAc - heptane gradient to give the title compound (2.63 g, 73 %) as an off white solid. MS: 288.0 (M+H+).
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 90.0℃;Inert atmosphere;	A mixture of 6-bromo-1-methyl-3,4-dihydroquinolin-2(1H)-one (Matrix Scientific, cat 101386: 0.4 g, 2 mmol), 4,4,5,5,4?,4?,5?,5?-octamethyl-[2,2?]bi[[1,3,2]dioxaborolanyl](630 mg, 2.5 mmol), [1,1?-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (70 mg, 0.08 mmol) and potassium acetate (490 mg, 5.0 mmol) in 1,4-dioxane (20 mL) was purged with nitrogen then heated at 90 C. overnight. After cooling it was concentrated. The crude material was purified by flash column eluting with 0 to 35% AcOEt in hexanes to give the desired product. LC-MS calculated for C16H23BNO3 (M+H)+: m/z=288.2. found 288.2.
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 90.0℃;Inert atmosphere;	A mixture of 6-bromo-1-methyl-3,4-dihydroquinolin-2(1H)-one (0.4 g, 2 mmol), 4,4,5,5,4?,4?,5?,5?-Octamethyl-[2,2?]bi[[1,3,2]dioxaborolanyl] (630 mg, 2.5 mmol), [1,1?-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) complexed with dichloromethane (1:1) (70 mg, 0.08 mmol) and potassium acetate (490 mg, 5.0 mmol) in 1,4-dioxane (20 mL) was purged with nitrogen and stirred at 90 C. overnight. After cooling to room temperature, the reaction mixture was concentrated. The residue was purified by flash chromatography eluting with 0 to 35% EtOAc in Hexanes to give the desired product. LC-MS calculated for C16H23BNO3 (M+H)+: m/z=288.2. found 288.1.

Reference： [1]Patent: US2013/72679,2013,A1 .Location in patent: Paragraph 0545; 0546
[2]Patent: WO2013/37779,2013,A1 .Location in patent: Page/Page column 74; 75
[3]Patent: WO2013/41591,2013,A1 .Location in patent: Page/Page column 65
[4]Patent: WO2014/139981,2014,A1 .Location in patent: Page/Page column 24; 25
[5]Patent: WO2016/66662,2016,A1 .Location in patent: Page/Page column 31
[6]Patent: WO2016/66597,2016,A1 .Location in patent: Page/Page column 37; 38
[7]Patent: US2016/9720,2016,A1 .Location in patent: Paragraph 0603
[8]Patent: US2016/9712,2016,A1 .Location in patent: Paragraph 0373

2
[ 1427587-32-3 ]
[ 1427585-00-9 ]

Reference： [1]Patent: WO2013/37779,2013,A1
[2]Patent: US2013/72679,2013,A1

3
[ 1427587-32-3 ]
[ 1427585-01-0 ]

Reference： [1]Patent: WO2013/37779,2013,A1
[2]Patent: US2013/72679,2013,A1

4
[ 1427587-32-3 ]
[ 1427585-03-2 ]

Reference： [1]Patent: WO2013/37779,2013,A1
[2]Patent: US2013/72679,2013,A1

5
[ 1427587-32-3 ]
[ 1427585-22-5 ]

Reference： [1]Patent: US2013/72679,2013,A1

6
[ 1427587-32-3 ]
[ 1427585-38-3 ]

Reference： [1]Patent: WO2013/37779,2013,A1
[2]Patent: US2013/72679,2013,A1

7
[ 1427587-32-3 ]
[ 1427587-26-5 ]

Reference： [1]Patent: US2013/72679,2013,A1

8
[ 1427587-32-3 ]
[ 1427587-35-6 ]
[ 1427587-36-7 ]

Yield	Reaction Conditions	Operation in experiment
90%	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In N,N-dimethyl-formamide; at 120.0℃; for 0.5h;Inert atmosphere; Microwave irradiation;	A microwave vial was charged with 3-bromo-5-[(S)-2-(tert-butyl-dimethyl-silanyloxymethyl)-pyrrolidin-1-yl]-pyridine (0.091 g, 0.245 mmol), <strong>[1427587-32-3]1-methyl-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,4-dihydro-1H-quinolin-2-one</strong> (intermediate A-1, 0.077 g, 0.270 mmol) and DMF (1.5 mL). The reaction mixture was purged with Argon; then, bis(triphenylphosphine)palladium(II)chloride (0.017 g, 0.025 mmol), followed by a 1N Na2CO3 aqueous solution (0.980 mL, 0.980 mmol) were added and the reaction mixture was heated in the microwave at 120 C. for 30 min. The reaction mixture was diluted with EtOAc, poured into aq. NaHCO3 (10 mL) and the aqueous layer was extracted with EtOAc (2×40 mL). Combined organics were washed with brine, dried over Na2SO4, filtered and evaporated. The residue was purified by silica gel flash chromatography eluting with a 0 to 5% MeOH-DCM gradient to give the title compound (0.1 g, 90%) as a white solid. MS: 452.1 (M+H+)
90%	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In water; N,N-dimethyl-formamide; at 120.0℃; for 0.5h;Microwave irradiation; Inert atmosphere;	[C] 6- {5-[(S)-2-(ter^Butyl-dimethyl-silanyloxymethyl)-pyrrolidin- 1 -yl]-pyridin-3-yl} - 1 - methyl-3,4-dihydro-lH-quinolin-2-oneA microwave vial was charged with 3-bromo-5-[(S)-2-(tert-butyl-dimethyl- silanyloxymethyl)-pyrrolidin-l-yl]-pyridine (0.091 g, 0.245 mmol), l-methyl-6-(4,4,5,5- tetramethyl-[l ,3,2]dioxaborolan-2-yl)-3,4-dihydro-lH-quinolin-2-one (intermediate A-1 , 0.077 g, 0.270 mmol) and DMF (1.5 mL). The reaction mixture was purged with Argon; then, ?z5(triphenylphosphine)palladium(II)chloride (0.017 g, 0.025 mmol), followed by a IN Na2C03 aqueous solution (0.980 mL, 0.980 mmol) were added and the reaction mixture was heated in the microwave at 120 C for 30 min. The reaction mixture was diluted with EtOAc, poured into aq. NaHC03 (10 mL) and the aqueous layer was extracted with EtOAc (2 x 40 mL). Combined organics were washed with brine, dried over Na2S04, filtered and evaporated. The residue was purified by silica gel flash chromatography eluting with a 0 to 5% MeOH-DCM gradient to give the title compound (0.1 g, 90%) as a white solid. MS: 452.1 (M+H+).

Reference： [1]Patent: US2013/72679,2013,A1 .Location in patent: Paragraph 0557; 0558
[2]Patent: WO2013/37779,2013,A1 .Location in patent: Page/Page column 78

9
[ 3279-90-1 ]
[ 1427587-32-3 ]

Reference： [1]Patent: WO2013/37779,2013,A1
[2]Patent: WO2013/41591,2013,A1
[3]Patent: WO2014/139981,2014,A1
[4]Patent: US2016/9712,2016,A1
[5]Patent: WO2016/66662,2016,A1
[6]Patent: WO2016/66597,2016,A1
[7]Patent: US2013/72679,2013,A1
[8]Patent: US2013/79365,2013,A1

10
[ 1427587-32-3 ]
[ 1428651-87-9 ]
[ 1428651-83-5 ]

Yield	Reaction Conditions	Operation in experiment
68%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; at 85.0℃;Inert atmosphere;	General procedure: [E] (rac)-6-(8-Amino-5,6,7,8-tetrahydroisoquinolin-4-yl)-1-methyl-3,4-dihydroquinolin-2(1H)-one[0353](rac)-4-bromo-5,6,7,8-tetrahydroisoquinolin-8-amine (745 mg, 3.28 mmol) and <strong>[1427587-32-3]1-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroquinolin-2(1H)-one</strong> (intermediate A-1) (1.13 g, 3.94 mmol) were dissolved in ethanol (60 mL) to give a light brown solution. Na2CO3 (382 mg, 3.61 mmol), dissolved in water (10 mL) was added followed by tetrakis(triphenylphosphine)palladium (0) (114 mg, 98.4 mumol) after evacuation and replacing 5 times with Argon. The solution was then heated at 85 C. overnight. The reaction was treated with an aq. 10% NaCl solution and extracted with AcOEt (3×). The organic phases were washed again with an aq. 10% NaCl solution, dried over Na2SO4, filtered and evaporated under reduced pressure to give 1.39 g brown foam which was purified by flash chromatography (50 g SiO2, Telos-cartridge, CH2Cl2/MeOH (3, 5, 7.5, 10 and 15%)) and precipitated from CH2Cl2 with n-pentane to give the title compound (690 mg, 68%) as a light brown foam. MS: 308.2 (M+H+).
68%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; at 85.0℃;Inert atmosphere;	[E] (rac)-6-(8-Amino-5,6,7,8-tetrahydroisoquinolin-4-yl)-l-methyl-3,4-dihydroquinolin- 2(lH)-oneIn a 100 mL round-bottomed flask, (rac)-4-bromo-5,6,7,8-tetrahydroisoquinolin-8-amine (745 mg, 3.28 mmol) and l-methyl-6-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)-3,4- dihydroquinolin-2(lH)-one (intermediate A-l) (1.13 g, 3.94 mmol) were dissolved in ethanol (60 mL) to give a light brown solution. Na2C03 (382 mg, 3.61 mmol), dissolved in water (10 mL) was added followed by tetra^'5(triphenylphosphine)palladium (0) (1 14 mg, 98.4 muiotaetaomicron?) after evacuation and replacing 5 times with Argon. The solution was then heated at 85 C overnight. The reaction was treated with an aq. 10% NaCl solution and extracted with AcOEt (3 x). The organic phases were washed again with an aq. 10 % NaCl solution, dried over Na2S04, filtered and evaporated under reduced pressure to give 1.39 g brown foam which was purified by flash chromatography (50 g Si02, Telos-cartridge, CH2Cl2/MeOH (3, 5, 7.5, 10 and 15%)) and precipitated from CH2C12 with n-pentane to give the title compound (690 mg, 68%) as a light brown foam. MS: 308.2 (M+H+).

Reference： [1]Patent: US2013/79365,2013,A1 .Location in patent: Paragraph 0353; 0354
[2]Patent: WO2013/41591,2013,A1 .Location in patent: Page/Page column 68

11
[ 1427587-32-3 ]
[ 1428652-15-6 ]

Reference： [1]Patent: WO2013/41591,2013,A1
[2]Patent: US2013/79365,2013,A1

12
[ 1427587-32-3 ]
[ 1428652-19-0 ]

Reference： [1]Patent: WO2013/41591,2013,A1
[2]Patent: US2013/79365,2013,A1

13
[ 1427587-32-3 ]
[ 1428652-26-9 ]

Reference： [1]Patent: WO2013/41591,2013,A1
[2]Patent: US2013/79365,2013,A1

14
[ 37669-64-0 ]
[ 1427587-32-3 ]
[ 1427588-22-4 ]

Yield	Reaction Conditions	Operation in experiment
97.5%	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In water; N,N-dimethyl-formamide; at 120.0℃; for 1.5h;Sealed tube; Inert atmosphere;	A sealed tube was charged with (5-bromo-pyridin-3-yl)-methanol (1 g, 5.32 mmol), l-methyl-6- (4,4,5 ,5-tetramethyl-[ 1 ,3 ,2]dioxaborolan-2-yl)-3 ,4-dihydro- 1 H-quinolin-2-one (intermediate A- 1 ) (1.6 g, 5.58 mmol) and DMF (15 mL). After purging the reaction mixture with argon, bi5'(triphenylphosphine)palladium(II)chloride (0.373 g, 0.532 mmol) and 1 M aq. Na2C03 solution (13.3 mL, 13.3 mmol) were added and the reaction was heated to 120 C for 1.5 h. The mixture was filtered over Dicalite, washed with EtOAc and the resulting filtrate was evaporated to dryness. The residue was purified by silica gel flash chromatography eluting with a 3 to 10% - MeOH-DCM gradient to give the title compound (1.392 g, 97.5 %) as a brown solid. MS: 269.5 (M+H+).
74%	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In N,N-dimethyl-formamide; at 120.0℃; for 0.833333h;Inert atmosphere; Microwave irradiation;	Example 2066-{5-[(3-Ethyl-oxetan-3-ylamino)-methyl]-pyridin-3-yl}-l-methyl-3,4-dihyd] quinolin-2-one [A] 6-(5 -Hydro xymethyl-pyridin-3-yl)- 1 -methyl-3 ,4-dihydro- lH-quinolin-2-oneA microwave vial was charged with (5-bromo-pyridin-3-yl)-methanol (376 mg, 2.0 mmol), l-methyl-6-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-3,4-dihydro-lH- quinolin-2-one (intermediate A-l) (574 mg, 2.0 mmol) and DMF (4 mL). After purging the reaction mixture with argon, ¾z'5(triphenylphosphine)palladium(II)chloride (140 mg, 0.2 mmol) and 2 N aq. Na2C03 solution (2.0 mL, 4 mmol) were added and the reaction was heated in the microwave at 120 C for 50 min. The reaction mixture was diluted with EtOAc, filtered through Dicalite and washed with EtOAc (2 x 20 mL). The resulting filtrate was washed with brine, dried over anhydrous Na2S04, filtered and evaporated to dryness. The residue was purified by silica gel flash chromatography eluting with a 0 to 5% MeOH-DCM gradient to give the title compound (198 mg, 74 %) as a white solid. MS: 269.2 (M+H+).

Reference： [1]Patent: WO2014/139981,2014,A1 .Location in patent: Page/Page column 26; 27
[2]Patent: US2013/72679,2013,A1 .Location in patent: Paragraph 0831; 0832
[3]Patent: WO2013/37779,2013,A1 .Location in patent: Page/Page column 221

15
[ 1427587-32-3 ]
[ 1427587-34-5 ]

Reference： [1]Patent: WO2013/37779,2013,A1

16
[ 1427587-32-3 ]
[ 1427584-65-3 ]

Reference： [1]Patent: WO2013/37779,2013,A1

17
[ 1427587-32-3 ]
[ 1427584-66-4 ]

Reference： [1]Patent: WO2013/37779,2013,A1

18
[ 1427587-32-3 ]
[ 1427587-88-9 ]

Reference： [1]Patent: WO2013/37779,2013,A1

19
[ 1427587-32-3 ]
[ 1427584-67-5 ]

Reference： [1]Patent: WO2013/37779,2013,A1

20
[ 1427587-32-3 ]
[ 1427588-24-6 ]

Reference： [1]Patent: WO2013/37779,2013,A1
[2]Patent: WO2014/139981,2014,A1
[3]Patent: US2013/72679,2013,A1

21
[ 1427587-32-3 ]
[ 1427586-71-7 ]

Reference： [1]Patent: WO2013/37779,2013,A1
[2]Patent: US2013/72679,2013,A1

22
[ 1427587-32-3 ]
[ 186593-31-7 ]
[ 1427585-08-7 ]

Yield	Reaction Conditions	Operation in experiment
86%	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In N,N-dimethyl-formamide; at 110.0℃; for 1.0h;	A sealed tube was charged with (S)-2-(5-bromo-pyridin-3-yloxymethyl)-azetidine-1-carboxylic acid tert-butyl ester (intermediate A-26, 0.260 g, 0.76 mmol), <strong>[1427587-32-3]1-methyl-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,4-dihydro-1H-quinolin-2-one</strong> (intermediate A-1, 0.239 g, 0.83 mmol) and DMF (3 mL). Then, bis(triphenylphosphine)palladium(II)chloride (0.053 g, 0.076 mmol), followed by 1N aqueous Na2CO3 solution (2.27 mL, 2.27 mmol) were added and the reaction was heated to 110 C. (pre-heated oil bath) for 1 h. The mixture was diluted with EtOAc, filtered through Dicalite and washed with EtOAc (20 mL). The resulting filtrate was poured into aq. NaHCO3 (20 mL) and the aqueous layer was extracted with EtOAc (20 mL). Combined organics were washed with brine, dried over Na2SO4, filtered and evaporated. The residue was purified by silica gel flash chromatography eluting with a 0 to 100% EtOAc-heptane gradient to give the title compound (0.277 g, 86%) as a light brown foam. MS: 424.1 (M+H+)
86%	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In N,N-dimethyl-formamide; at 110.0℃; for 1.0h;Sealed tube;	Example 45 (S)-2-[5-(l-Methyl-2-oxo-l,2,3,4-tetrahydro-quinolin-6-yl)-pyridin-3-yloxymethyl]- azetidine-l-carboxylic acid tert-butyl ester A sealed tube was charged with (S)-2-(5-bromo-pyridin-3-yloxymethyl)-azetidine-l- carboxylic acid tert-butyl ester (intermediate A-26, 0.260 g, 0.76 mmol), l-methyl-6- (4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-3,4-dihydro-lH-quinolin-2-one(intermediate A-l, 0.239 g, 0.83 mmol) and DMF (3 mL). Then,?z'5(triphenylphosphine)palladium(II)chloride (0.053 g, 0.076 mmol), followed by IN aqueous Na2C03 solution (2.27 mL, 2.27 mmol) were added and the reaction was heated to 110 C (pre-heated oil bath) for lh. The mixture was diluted with EtO Ac, filtered through Dicalite and washed with EtO Ac (20 mL). The resulting filtrate was poured into aq. NaHC03 (20 mL) and the aqueous layer was extracted with EtO Ac (20 mL).Combined organics were washed with brine, dried over Na2S04, filtered and evaporated. The residue was purified by silica gel flash chromatography eluting with a 0 to 100 % EtO Ac-heptane gradient to give the title compound (0.277 g, 86%) as a light brown foam. MS: 424.1 (M+H+).

Reference： [1]Patent: US2013/72679,2013,A1 .Location in patent: Paragraph 0781; 0782
[2]Patent: WO2013/37779,2013,A1 .Location in patent: Page/Page column 139; 140

23
[ 1427587-32-3 ]
[ 873302-39-7 ]
2,2-dimethyl-N-[5-(1-methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-6-yl)-pyridin-3-yl]-propionamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	With bis-triphenylphosphine-palladium(II) chloride; In N,N-dimethyl-formamide; at 0.12℃; for 0.08333330000000001h;Inert atmosphere; Microwave irradiation;	A microwave vial was charged with N-(5-bromopyridin-3-yl)pivalamide (0.2 g, 0.778 mmol), <strong>[1427587-32-3]1-methyl-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,4-dihydro-1H-quinolin-2-one</strong> (intermediate A-1) (0.246 g, 0.856 mmol) and DMF (4 mL). The reaction mixture was purged with Argon; then, bis(triphenylphosphine)palladium(II)chloride (0.055 g, 0.078 mmol), followed by 1N aqueous Na2CO3 solution (2.33 mL, 2.33 mmol) were added and the reaction was heated in the microwave at 120 C. for 5 min. The reaction mixture was diluted with EtOAc, filtered through Dicalite and washed with EtOAc (2×20 mL). The resulting filtrate was washed with brine, dried over Na2SO4, filtered and evaporated to dryness. The residue was purified by silica gel flash chromatography eluting with a 0 to 5% MeOH-DCM gradient to give the title compound (0.195 g, 74%) as a white solid. MS: 338.2 (M+H+)
74%	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In N,N-dimethyl-formamide; at 120.0℃; for 0.08333330000000001h;Microwave irradiation; Inert atmosphere;	Intermediate A-26-(5-Amino-pyridin-3-yl)-l-methyl-3,4-dihydro-lH-quinolin-2-one hydrochloride[A] 2,2-Dimethyl-N-[5-(l-methyl-2-oxo-l,2J^-tetrahydro-quinolin-6-yl)-pyridin-3-yl]- propionamideA microwave vial was charged with N-(5-bromopyridin-3-yl)pivalamide (0.2 g, 0.778 mmol), l-methyl-6-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-3,4-dihydro-lH- quinolin-2-one (intermediate A-1) (0.246 g, 0.856 mmol) and DMF (4 mL). The reaction mixture was purged with Argon; then, ?z'5(triphenylphosphine)palladium(II)chloride (0.055 g, 0.078 mmol), followed by IN aqueous Na2C03 solution (2.33 mL, 2.33 mmol) were added and the reaction was heated in the microwave at 120 C for 5 min. The reaction mixture was diluted with EtOAc, filtered through Dicalite and washed with EtOAc (2 x 20 mL). The resulting filtrate was washed with brine, dried over Na2S04, filtered and evaporated to dryness. The residue was purified by silica gel flash chromatography eluting with a 0 to 5% MeOH-DCM gradient to give the title compound (0.195 g, 74 %) as a white solid. MS: 338.2 (M+H+).

Reference： [1]Patent: US2013/72679,2013,A1 .Location in patent: Paragraph 0548; 0549
[2]Patent: WO2013/37779,2013,A1 .Location in patent: Page/Page column 75; 76

24
[ 135124-70-8 ]
[ 1427587-32-3 ]
[ 1427584-99-3 ]

Yield	Reaction Conditions	Operation in experiment
94%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; at 85.0℃;	A round-bottomed flask was charged with 5-bromo-pyridin-3-yl-methylamine (0.5 g, 2.67 mmol), <strong>[1427587-32-3]1-methyl-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,4-dihydro-1H-quinolin-2-one</strong> (intermediate A-1, 0.845 g, 2.94 mmol) and EtOH (48 mL). Then, tetrakis(triphenylphosphine)palladium(0) (0.093 g, 0.080 mmol), followed by aqueous Na2CO3 solution (8 mL, 0.312 g, 2.94 mmol) were added and the reaction mixture heated to 85 C. over night. The mixture was evaporated to dryness, the residue was taken up in EtOAc, filtered through Dicalite and washed with EtOAc (2×50 mL). The filtrate was evaporated to dryness. Then, the residue was purified by silica gel flash chromatography eluting with a 0 to 20% MeOH(1% NH4OH)-DCM gradient to give the title compound (0.7 g, 94%) as an off white solid. MS: 268.2 (M+H+)
94%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; at 85.0℃;	Example 366-(5-Aminomethyl-pyridin-3-yl)-l-methyl-3,4-dihydro-lH-quinolinA round-bottomed flask was charged with 5-bromo-pyridin-3-yl-methylamine (0.5 g, 2.67 mmol), l-methyl-6-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-3,4-dihydro-lH- quinolin-2-one (intermediate A-l, 0.845 g, 2.94 mmol) and EtOH (48 mL). Then, tetra^'5(triphenylphosphine)palladium(0) (0.093 g, 0.080 mmol), followed by aqueous Na2C03 solution (8 mL, 0.312 g, 2.94 mmol) were added and the reaction mixture heated to 85 C over night. The mixture was evaporated to dryness, the residue was taken up in EtOAc, filtered through Dicalite and washed with EtOAc (2 x 50 mL). The filtrate was evaporated to dryness. Then, the residue was purified by silica gel flash chromatography eluting with a 0 to 20% MeOH(l% NH4OH)-DCM gradient to give the title compound (0.7 g, 94 %) as an off white solid. MS: 268.2 (M+H+).

Reference： [1]Patent: US2013/72679,2013,A1 .Location in patent: Paragraph 0763; 0764
[2]Patent: WO2013/37779,2013,A1 .Location in patent: Page/Page column 134; 135

25
[ 1255871-43-2 ]
[ 1427587-32-3 ]
[ 1427588-15-5 ]

Yield	Reaction Conditions	Operation in experiment
100%	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In N,N-dimethyl-formamide; at 120.0℃; for 1.0h;	A flask was charged with potassium 1-(5-bromopyridin-3-yl)cyclopropanecarboxylate (0.5 g, 1.52 mmol), <strong>[1427587-32-3]1-methyl-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,4-dihydro-1H-quinolin-2-one</strong> (intermediate A-1, 0.479 g, 1.67 mmol) and DMF (7 mL). Then, bis(triphenylphosphine)palladium(II)chloride (0.106 g, 0.152 mmol), followed by 1N aqueous Na2CO3 solution (3.64 mL, 2.4 mmol) were added and the reaction was heated to 120 C. (pre-heated oil bath) for 1 h. The mixture was evaporated to dryness and the residue purified by silica gel flash chromatography eluting with a 0 to 15% MeOH-DCM gradient to give the title compound (0.551 g, 100%) as a brown solid. MS: 323.4 (M+H+)
100%	With bis-triphenylphosphine-palladium(II) chloride; water; sodium carbonate; In N,N-dimethyl-formamide; at 120.0℃; for 1.0h;	[C] l-(5-(l-Methyl-2-oxo-l,2J^-tetrahydroquinolin-6-yl)pyridin-3yl)cyclopropane- carboxylic acidA flask was charged with potassium l-(5-bromopyridin-3-yl)cyclopropanecarboxylate (0.5 g, 1.52 mmol), l-methyl-6-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-3,4-dihydro-lH- quinolin-2-one (intermediate A-l, 0.479 g, 1.67 mmol) and DMF (7 mL). Then,?z'5(triphenylphosphine)palladium(II)chloride (0.106 g, 0.152 mmol), followed by IN aqueous Na2C03 solution (3.64 mL, 2.4 mmol) were added and the reaction was heated to 120 C (pre-heated oil bath) for lh. The mixture was evaporated to dryness and the residue purified by silica gel flash chromatography eluting with a 0 to 15 % MeOH-DCM gradient to give the title compound (0.551 g, 100%) as a brown solid. MS: 323.4 (M+H+).

Reference： [1]Patent: US2013/72679,2013,A1 .Location in patent: Paragraph 0789; 0790
[2]Patent: WO2013/37779,2013,A1 .Location in patent: Page/Page column 148; 149

26
[ 1427587-32-3 ]
[ 1428652-16-7 ]
[ 1428652-17-8 ]

Reference： [1]Patent: US2013/79365,2013,A1

27
[ 1427587-32-3 ]
[ 1428652-20-3 ]
[ 1428652-21-4 ]

Reference： [1]Patent: US2013/79365,2013,A1

28
[ 1427587-32-3 ]
6-[1-(2-amino-ethyl)-1,2,3,4-tetrahydro-[1,7]naphthyridin-5-yl]-1-methyl-3,4-dihydro-1H-quinolin-2-one hydrochloride [ No CAS ]

Reference： [1]Patent: WO2013/41591,2013,A1

29
[ 1427587-32-3 ]
[ 1428652-28-1 ]

Reference： [1]Patent: WO2013/41591,2013,A1

30
[ 1427587-32-3 ]
[ 1428652-29-2 ]

Reference： [1]Patent: WO2013/41591,2013,A1

31
[ 1427587-32-3 ]
[ 1428652-30-5 ]

Reference： [1]Patent: WO2013/41591,2013,A1
[2]Patent: US2013/79365,2013,A1

32
[ 1427587-32-3 ]
[ 1428652-31-6 ]

Reference： [1]Patent: WO2013/41591,2013,A1
[2]Patent: US2013/79365,2013,A1

33
[ 1427587-32-3 ]
[ 1428652-34-9 ]
[ 1428652-33-8 ]

Reference： [1]Patent: WO2013/41591,2013,A1
[2]Patent: US2013/79365,2013,A1

34
[ 1427587-32-3 ]
[ 1428651-91-5 ]
[ 1428651-92-6 ]

Yield	Reaction Conditions	Operation in experiment
14%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; at 85.0℃;Inert atmosphere;	General procedure: Intermediate A-4(rac)-6-(7-Amino-6,7-dihydro-5H-cyclopenta[c]pyridin-4-yl)-1-methyl-3,4-dihydroquinolin-2(1H)-one[0365](rac)-4-bromo-6,7-dihydro-5H-cyclopenta[c]pyridin-7-amine (intermediate A-3[C]) (107 mg, 500 mumol) and <strong>[1427587-32-3]1-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroquinolin-2(1H)-one</strong> (intermediate A-1) (172 mg, 600 mumol) were dissolved in EtOH (9 mL) to give a brown solution. Na2CO3 (58.3 mg, 550 mumol), dissolved in water (1.5 mL) was added followed by tetrakis(triphenylphosphine)palladium (0) (17.3 mg, 15.0 mmol) after evacuation and replacing 5 times with Argon. The suspension was then heated at 85 C. overnight. A aq. 10% NaCl solution was added at RT, and the mixture was extracted with AcOEt (3×). The organic fractions were washed again with aq. 10% NaCl solution, dried over Na2SO4, filtered, evaporated and purified by flash chromatography (50 g SiO2, Telos-cartridge, CH2Cl2/MeOH (2%)) to afford the title compound (21 mg, 14%) as a dark green powder. MS: 294.2 (M+H+)

Reference： [1]Patent: US2013/79365,2013,A1 .Location in patent: Paragraph 0365; 0366

35
[ 1427587-32-3 ]
[ 1432064-93-1 ]
[ 1428651-93-7 ]

Yield	Reaction Conditions	Operation in experiment
72%	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In water; N,N-dimethyl-formamide; at 120.0℃; for 0.5h;Inert atmosphere; Microwave irradiation;	Intermediate A-51-Methyl-6-(1,2,3,4-tetrahydro-1,7-naphthyridin-5-yl)-3,4-dihydroquinolin-2(1H)-one[0367]5-bromo-1,2,3,4-tetrahydro-1,7-naphthyridine hydrochloride (0.1 g, 0.401 mmol), <strong>[1427587-32-3]1-methyl-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,4-dihydro-1H-quinolin-2-one</strong> (intermediate A-1, 0.127 g, 0.441 mmol) and DMF (2.5 mL). The reaction mixture was purged with Argon. Then, bis(triphenylphosphine)palladium(II)chloride (0.028 g, 0.040 mmol), followed by a 1N aqueous Na2CO3 solution (1.6 mL, 1.6 mmol) were added and the reaction mixture was heated in the microwave at 120 C. for 30 min. The reaction mixture was diluted with EtOAc, filtered through Dicalite and washed with EtOAc (2×20 mL). The resulting filtrate was washed with brine, dried over Na2SO4, filtered and evaporated to dryness. The residue was purified by silica gel flash chromatography eluting with a 0 to 5% MeOH-DCM gradient to give the title compound (0.085 g, 72%) as a white solid. MS: 294.2 (M+H+)

Reference： [1]Patent: US2013/79365,2013,A1 .Location in patent: Paragraph 0367; 0368

36
[ 1427587-32-3 ]
[ 1428652-07-6 ]
(+)-N-[(7SR,8RS)-7-methyl-4-(1-methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-6-yl)-5,6,7,8-tetrahydro-isoquinolin-8-yl]-propionamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
23.8%	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In water; N,N-dimethyl-formamide; at 100.0℃; for 0.5h;Inert atmosphere; Microwave irradiation;	General procedure: (+)-N-[(7S,8R or 7R,8S)-7-Methyl-4-(1-methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-6-yl)-5,6,7,8-tetrahydro-isoquinolin-8-yl]-propionamide[0507](+)-N-((7S,8R or 7R,8S)-4-bromo-7-methyl-5,6,7,8-tetrahydro-isoquinolin-8-yl)-propionamide (50 mg, 0.168 mmol) (intermediate B-6c) and 1-methyl-6-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-yl)-3,4-dihydro-1H-quinolin-2-one (53 mg, 0.185 mmol) (intermediate A-1) in DMF (1.5 mL) was purged with argon for 1 min before bis(triphenylphosphine)palladium (II)chloride (12 mg, 0.017 mmol) and 2 N aq. Na2CO3 solution (0.168 mL, 0.336 mmol) were added. The resulting reaction mixture was purged with argon for 2 min and then heated at 100 C. for 30 min in a microwave. After cooling to room temperature, the reaction mixture was diluted with EtOAc (5 mL), filtered through Dicalite and washed with EtOAc (2×20 mL). The resulting filtrate was washed with brine, dried over anhy. Na2SO4, filtered and evaporated to dryness. The crude product was then purified by Prep-HPLC to give title compound (15 mg, 23.8%) as a white foam. MS: 378.1 (M+H)+.

Reference： [1]Patent: US2013/79365,2013,A1 .Location in patent: Paragraph 0507; 0508

37
[ 742100-16-9 ]
[ 73183-34-3 ]
[ 1427587-32-3 ]

Yield	Reaction Conditions	Operation in experiment
73%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 80.0℃;Inert atmosphere;	[B] 1-Methyl-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,4-dihydro-1H-quinolin-2-one[0342]6-bromo-1-methyl-3,4-dihydro-1H-quinolin-2-one (3 g, 12.5 mmol), 4,4,4?,4?,5,5,5?,5?-octamethyl-2,2?-bi(1,3,2-dioxaborolane) (3.81 g, 15.0 mmol), potassium acetate (3.68 g, 37.5 mmol) and dioxane (48 mL). The mixture was purged with Ar, then dichloro[1,1?-bis(diphenylphosphino)-ferrocene]palladium(II) dichloromethane complex (1:1) [PdCl2(DPPF)-CH2Cl2 adduct] (457 mg, 0.625 mmol) was added and the resulting mixture was heated to 80 C. over night. The reaction mixture was diluted with EtOAc, filtered through Dicalite and washed with EtOAc (2×150 mL). The resulting filtrate was washed with brine, dried over Na2SO4, filtered and evaporated to dryness. The residue was purified by silica gel flash chromatography eluting with a 0 to 40% EtOAc-heptane gradient to give the title compound (2.63 g, 73%) as an off white solid. MS: 288.0 (M+H+).

Reference： [1]Patent: US2013/79365,2013,A1 .Location in patent: Paragraph 0342; 0343

38
[ 1255871-43-2 ]
[ 1427587-32-3 ]
[ 1427585-22-5 ]

Reference： [1]Patent: WO2013/37779,2013,A1

39
[ 1427587-32-3 ]
[ 1428651-88-0 ]
[ 1428651-92-6 ]

Yield	Reaction Conditions	Operation in experiment
14%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; at 85.0℃;Inert atmosphere;	Intermediate A-4(rac)-6-(7-Amino-6,7-dihydro-5H-cyclopenta[c]pyridin-4-yl)-l-methyl-3,4- dihydroquinolin-2(lH)-oneIn a 50 ml round-bottomed flask, (rac)-4-bromo-6,7-dihydro-5H-cyclopenta[c]pyridin-7- amine (intermediate A-3[C]) (107 mg, 500 muiotaetaomicron?) and l-methyl-6-(4,4,5,5-tetramethyl- l,3,2-dioxaborolan-2-yl)-3,4-dihydroquinolin-2(lH)-one (intermediate A-l) (172 mg, 600 muiotaetaomicron?) were dissolved in EtOH (9 mL) to give a brown solution. Na2C03 (58.3 mg, 550 muiotaetaomicron?), dissolved in water (1.5 mL) was added followed bytetra^'5(triphenylphosphine)palladium (0) (17.3 mg, 15.0 muiotaetaomicron?) after evacuation and replacing 5 times with Argon. The suspension was then heated at 85 C overnight. A aq. 10 % NaCl solution was added at RT, and the mixture was extracted with AcOEt (3 x). The organic fractions were washed again with aq. 10 %> NaCl solution, dried over Na2S04, filtered, evaporated and purified by flash chromatography (50 g S1O2, Telos-cartridge, CH2Cl2/MeOH (2%)) to afford the title compound (21 mg, 14%) as a dark green powder. MS: 294.2 (M+H+)

Reference： [1]Patent: WO2013/41591,2013,A1 .Location in patent: Page/Page column 71; 72

40
[ 1427587-32-3 ]
5-bromo-1,2,3,4-tetrahydro-1,7-naphthyridine hydrochloride [ No CAS ]
[ 1428651-93-7 ]

Yield	Reaction Conditions	Operation in experiment
72%	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In water; N,N-dimethyl-formamide; at 120.0℃; for 0.5h;Inert atmosphere; Microwave irradiation;	Intermediate A-5 l-Methyl-6-(l,2,3,4-tetrahydro-l,7-naphthyridin-5-yl)-3,4-dihydroquinolin-2(lH)-A microwave vial was charged with 5-bromo-l,2,3,4-tetrahydro-l,7-naphthyridine hydrochloride (0.1 g, 0.401 mmol), l-methyl-6-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan- 2-yl)-3,4-dihydro-lH-quinolin-2-one (intermediate A-1, 0.127 g, 0.441 mmol) and DMF (2.5 mL). The reaction mixture was purged with Argon. Then,¾z'5(triphenylphosphine)palladium(II)chloride (0.028 g, 0.040 mmol), followed by a IN aqueous Na2C03 solution (1.6 mL, 1.6 mmol) were added and the reaction mixture was heated in the microwave at 120 C for 30 min. The reaction mixture was diluted with EtOAc, filtered through Dicalite and washed with EtOAc (2 x 20 mL). The resulting filtrate was washed with brine, dried over Na2S04, filtered and evaporated to dryness. The residue was purified by silica gel flash chromatography eluting with a 0 to 5% MeOH- DCM gradient to give the title compound (0.085 g, 72 %) as a white solid. MS: 294.2 (M+H+).

Reference： [1]Patent: WO2013/41591,2013,A1 .Location in patent: Page/Page column 72

41
[ 1427587-32-3 ]
(-)-rel-(R)-N-(4-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-5,6,7,8-tetrahydroisoquinolin-8-yl)propionamide [ No CAS ]
(+)-rel-(S)-N-(4-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-5,6,7,8-tetrahydroisoquinolin-8-yl)propionamide [ No CAS ]

Reference： [1]Patent: WO2013/41591,2013,A1

42
[ 1427587-32-3 ]
(-)-rel-(R)-N-(4-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-5,6,7,8-tetrahydroisoquinolin-8-yl)ethanesulfonamide [ No CAS ]
(+)-rel-(S)-N-(4-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-5,6,7,8-tetrahydroisoquinolin-8-yl)ethanesulfonamide [ No CAS ]

Reference： [1]Patent: WO2013/41591,2013,A1

43
[ 1427587-32-3 ]
(+)-rel-N-((7S,8R)-4-bromo-7-methyl-5,6,7,8-tetrahydro-isoquinolin-8-yl)-propionamide [ No CAS ]
(+)-N-[rel-(7S,8R)-7-methyl-4-(1-methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-6-yl)-5,6,7,8-tetrahydro-isoquinolin-8-yl]-propionamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
23.8%	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In N,N-dimethyl-formamide; at 100.0℃; for 0.5h;Inert atmosphere; Microwave irradiation;	Example 42(+)- V-[(7S,8R or 7R,8S)-7-Methyl-4-(l-methyl-2-oxo-l,2,3,4-tetrahydro-quinolin-6- yl)-5,6,7,8-tetrahydro-isoquinolin-8-yl]-propionamideA mixture of (+)-N-((7S,8R or 7R,8S)-4-bromo-7-methyl-5,6,7,8-tetrahydro-isoquinolin-8- yl)-propionamide (50 mg, 0.168 mmol) (intermediate B-6c) and l-methyl-6-(4,4,5,5- tetramethyl-[l ,3,2]- dioxaborolan-2-yl)-3,4-dihydro-lH-quinolin-2-one (53 mg, 0.185 mmol) (intermediate A-l) in DMF (1.5 mL) was purged with argon for 1 min before ?z'5(triphenylphosphine)palladium (Il)chloride (12 mg, 0.017 mmol) and 2 N aq. Na2C03 solution (0.168 mL, 0.336 mmol) were added. The resulting reaction mixture was purged with argon for 2 min and then heated at 100 C for 30 min in a microwave. After cooling to room temperature, the reaction mixture was diluted with EtOAc (5 mL), filtered through Dicalite and washed with EtOAc (2 x 20 mL). The resulting filtrate was washed with brine, dried over anhy. Na2S04, filtered and evaporated to dryness. The crude product was then purified by Prep-HPLC to give title compound (15 mg, 23.8 %) as a white foam. MS: 378.1 (M+H)+.

Reference： [1]Patent: WO2013/41591,2013,A1 .Location in patent: Page/Page column 115

44
[ 1427587-32-3 ]
6-[5-(5-fluoro-2-oxo-2H-pyridin-1-ylmethyl)-pyridin-3-yl]-1-methyl-3,4-dihydro-1H-quinolin-2-one [ No CAS ]
6-[5-(5-fluoro-pyridin-2-yloxymethyl)-pyridin-3-yl]-1-methyl-3,4-dihydro-1H-quinolin-2-one [ No CAS ]