Name: 1425970-61-1|tert-Butyl 4-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene)piperidine-1-carboxylate|98%
Brand: Ambeed
SKU: A925071
Rating: 91 (40 reviews)

1
[ 26218-78-0 ]
[ 1425970-61-1 ]
[ 1425970-62-2 ]

Yield	Reaction Conditions	Operation in experiment
33%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate In 1,4-dioxane; water at 80℃; for 18h;	2.33.b Step b Intermediate 27 MethyI-6-[l-(tert-butoxycarbonyl)piperidin-4-ylidene]methyl}pyridine-3-carboxylate Step b Intermediate 27 MethyI-6-[l-(tert-butoxycarbonyl)piperidin-4-ylidene]methyl}pyridine-3-carboxylate A mixture of ferf-butyl 4-[(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2- yl)methylidene]piperidine-l -carboxylate (Int 26) (660 mg, 2.04 mmol) and methyl 6- bromopyridine-3-carboxylate (563mg, 2.14mmol) in dioxane (5 ml) and sat. aq. Na2C03 (1 ml) was degassed for 10 min. PdCl2(dppf) (149 mg, 0.02 mmol) was then added and the reaction heated to 80 °C for 18 h. The reaction mixture was allowed to cool to r.t. and was filtered through a pad of celite, washing with EtOAc. The filtrate was concentrated under reduced pressure and purified by column chromatography (Si0 ; 10 % diethyl ether in DCM) to give methyl 6-[l-(tert-butoxycarbonyl)piperidin- 4-ylidene]methyl}pyridine-3-carboxylate as a pale yellow oil (223 mg, 33 %). Ή NMR (300MHz, CDC13) δ 8.59 (s, 1 H), 8.09 (d, J = 6.8 Hz, 1H), 7.64 (d, J = 6.8 Hz, 1H), 6.34 (s, 1H), 3.99 (s, 3H), 3.52 (t, J = 4.5 Hz, 2H), 3.41 (t, J = 4.5 Hz, 2H), 2.43 (t, J = 4.5 Hz, 2H), 2.36 (t, J = 4.5 Hz, 2H), 1.46 (s, 9H)

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - WO2013/27001, 2013, A1 Location in patent: Page/Page column 70

2
[ 624-28-2 ]
[ 1425970-61-1 ]
[ 1425972-48-0 ]

Yield	Reaction Conditions	Operation in experiment
27%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate In 1,4-dioxane; water at 100℃; for 0.333333h; Microwave irradiation;	2.162.a Step a Intermediate 186 tert-Butyl 4-[(5-bromopyridin-2-yl)methylidene]piperidine-l-carboxylate Step a Intermediate 186 tert-Butyl 4-[(5-bromopyridin-2-yl)methylidene]piperidine-l-carboxylate A mixture of 2,5-dibromopyridine (1.61 g, 6.81 mmol), tert-butyl 4-((4,4,5,5- tetramethyl-l ,3,2-dioxaborolan-2-yl)methylene)piperidine-l-carboxylate (Int 26) (2.20 g, 6.81 mmol), potassium phosphate (1.45 g, 6.81 mmol) and PdCl2(dppf) (0.498 g, 0.681 mmol) in 1 , 4-dioxane (7 ml) and water (7 ml) was heated in the microwave at 100 °C for 20 min. Water was added and the mixture extracted with EtOAc, dried (MgS04), concentrated under reduced pressure and purified by column chromatography (Si02; 0 - 20 % EtOAc in petrol) to give tert-butyl 4-[(5-bromopyridin-2- yl)methylidene]piperidine-l-carboxylate as a yellow solid (645 mg, 27 %). Ή NMR (400 MHz, DMSCW6) δ 8.64 (m, 1H), 7.98 (m, 1H), 7.26 (m, 1H), 6.35 (s, 1H), 3.44 (m, 2H), 3.37 (m, 2H), 2.87 (m, 2H), 2.31 (m, 2H), 1.42 (s, 9H) MS ES+ 253/255

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - WO2013/27001, 2013, A1 Location in patent: Page/Page column 170

3
[ 1021169-68-5 ]
[ 1425970-61-1 ]
[ 1425972-75-3 ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium carbonate In 1,4-dioxane; water at 100℃; for 0.75h; Sealed tube; Microwave irradiation; Inert atmosphere;	2.173.c Step c Intermediate 202 tert-Buryl 4-[4-(tetrahydro-2H-pyran-4-ylsulfonyl)benzylidene]piperidine-l -carboxylate Step c Intermediate 202 tert-Buryl 4-[4-(tetrahydro-2H-pyran-4-ylsulfonyl)benzylidene]piperidine-l -carboxylate A microwave vial was charged with 4-(4-bromophenylsulfonyl)tetrahydro-2H-pyran (Int 201) (598 mg, 2.0 mmol), reri-butyl 4-((4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2- yl)methylene)piperidine- l-carboxylate (Int 26) (950 mg, 2.9 mmol), and potassium carbonate (1.083 g, 7.84 mmol) in 1 ,4-Dioxane : ¾0 (4 ml : 4 ml). The vial was sealed and purged with nitrogen then Pd(PPh3)4 (226 mg, 0.2 mmol) was added and mixture irradiated in the microwave for 45 min at 100 °C. Mixture was quenched by the addition of sat. aq. NaHC03 and extracted with EtOAc (x 2). The organics were washed with brine, dried (MgSO_i) and concentrated under reduced pressure. Residue was purified by column chromatography (Si02; 0 - 50 % EtOAc in petrol) to yield tert-butyl 4-[4-(tetrahydro-2H-pyran-4-ylsulfonyl)benzylidene]piperidine-l -carboxylate as a white solid. MS ES+ 422

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - WO2013/27001, 2013, A1 Location in patent: Page/Page column 186-187

4
[ 305794-65-4 ]
[ 1425970-61-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: ammonium chloride / tetrahydrofuran; methanol / 0.5 h / 0 °C / Inert atmosphere 1.2: 20 °C 2.1: triphenylphosphine; potassium acetate; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾ / 1,4-dioxane / Reflux
	Multi-step reaction with 2 steps 1.1: ammonium chloride / tetrahydrofuran; methanol / 0.5 h / 0 °C / Inert atmosphere 1.2: 4 h / 20 °C / Inert atmosphere 2.1: tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; potassium acetate; triphenylphosphine / 1,4-dioxane / Inert atmosphere; Reflux

Reference： [1]Current Patent Assignee: CANCER THERAPEUTICS CRC PTY LTD - WO2017/153520, 2017, A1
[2]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - WO2013/27001, 2013, A1

5
[ 1020329-80-9 ]
[ 73183-34-3 ]
[ 1425970-61-1 ]

Yield	Reaction Conditions	Operation in experiment
43%	With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; anhydrous potassium acetate; triphenylphosphine In 1,4-dioxane Reflux;	viii.c (c) tert-Butyl 4-((4, 4,5, 5-tetramethyl- 1,3, 2-dioxaborolan-2-yI)methylene)piperidine- 1-carboxylate (122) To a solution of tert-butyl 4-(bromomethylene)piperidine-1-carboxylate 121 (3.0 g, 10.86 mmol) in 1 ,4-dioxane (30 mL) was added 4,4,4’,4’,5,5,5’,5’-octamethyl-2,2’-bi(1 ,3,2- dioxaborolane) (4.2 g, 16.29 mmol), KOAc (2.1 g, 21.72 mmol), PPh3 (171 mg, 0.652 mmol) and Pd2(dba)3 (298 mg, 0.326 mmol). The reaction was heated at reflux overnight thencooled to room temperature and the solids removed by filtration through Celite. The filtrate was concentrated and the residue partitioned between DCM (20 mL) and water (20 mL) and the aqueous phase extracted with DCM (3 x 10 mL). The combined organic extracts were washed with brine (3 x 10 mL), dried (Na2SO4), filtered and concentrated. The residue obtained was purified by column chromatography (EtOAc/petroleum ether=1/20 v/v) to givethe title compound (1.52 g, 43%) as an off-white solid. 1H NMR (400MHz, ODd3) 65.14 (s,1 H), 3.45-3.41 (m, 4H), 2.58 (t, J = 5.6 Hz, 2H), 2.24 (t, J = 5.6 Hz, 2H), 1.45 (s, 9H), 1.25 (s,12H); LCMS RT 3.31 mm; m/z 346.2 [M+Na].
41%	With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; anhydrous potassium acetate; triphenylphosphine In 1,4-dioxane Inert atmosphere; Reflux;	2.33.a Step a Intermediate 26 /ert-Butyl 4-[(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)methylidene]piperidine-l - carbox late Step a Intermediate 26 /ert-Butyl 4-[(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)methylidene]piperidine-l - carbox late tert-Butyl 4-(bromomethylidene)piperidine-l -carboxylate (3.00 g, 10.9 mmol), bis(pinacolato)diboron (4.1 g, 16 mmol), KOAc (1.9 g, 19.6 mmol), triphenylphosphine (185 mg, 0.65 mmol) and Pd2dba3 (300 mg, 0.33 mmol) were stirred in dioxane (50 ml) and degassed by bubbling Ar through the mixture for 20 min. The mixture was then heated at reflux overnight. The solution was cooled and the dioxane removed under reduced pressure. The residue was purified by column chromatography (Si02; 20; 1 heptane/ethyl acetate) to give tert-butyl 4-[(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2- yl)methylidene]piperidine-l -carboxylate as a white solid (1.45 g, 41 %). JH NM (300 MHz, CDC13) δ 5.14 (s, 1H), 3.43 (m, 4H), 2.59 (m, 2H), 1.41 (s, 9H), 1.25 (s, 18 H)
41%	With palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; anhydrous potassium acetate In 1,4-dioxane at 80℃; for 16h; Inert atmosphere;	18 Tert-butyl 4-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylidene]piperidine-1- carboxylate. To a stirred solution/mixture of tert-butyl 4-(bromomethylidene)piperidine-1- carboxylate (2.50 g, 9.052 mmol, 1 equiv.) and bis(pinacolato)diboron (3.45 g, 13.578 mmol, 1.5 equiv.) in 1,4-dioxane were added Pd(dppf)Cl2 (0.66 g, 0.905 mmol, 0.10 equiv.) and KOAc (2.67 g, 27.157 mmol, 3 equiv.) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 16 hours at 80 C under nitrogen atmosphere. The reaction was quenched with Water at room temperature. The resulting mixture was extracted with EtOAc (3 x 30 mL). The combined organic layers were washed with brine (2 x 20 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE/EtOAc (5:1) to afford tert-butyl 4- [(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylidene]piperidine-1-carboxylate (1.2 g, 41%) as an off-white solid.

41%	With palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; anhydrous potassium acetate In 1,4-dioxane at 80℃; for 16h; Inert atmosphere;	18 tert-butyl 4-[(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)methylidene]piperidine-1-carboxylate To a stirred solution/mixture of tert-butyl 4-(bromomethylidene)piperidine-1-carboxylate (2.50 g, 9.052 mmol, 1 equiv) and bis(pinacolato)diboron (3.45 g, 13.578 mmol, 1.5 equiv) in 1,4-dioxane were added Pd(dppf)Cl2 (0.66 g, 0.905 mmol, 0.10 equiv) and KOAc (2.67 g, 27.157 mmol, 3 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 16 hours at 80 °C under nitrogen atmosphere. The reaction was quenched with Water at room temperature. The resulting mixture was extracted with EtOAc (3 x 30 mL). The combined organic layers were washed with brine (2 x 20 mL), dried over anhydrous Na2SC>4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluting with petroleum ether/EtOAc (5:1) to afford tert-butyl 4-[(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)methylidene]piperidine-1-carboxylate (1.2 g, 41%) as an off-white solid.
41%	With palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; anhydrous potassium acetate In 1,4-dioxane at 80℃; for 16h; Inert atmosphere;	18 tert-butyl 4-[(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)methylidene]piperidine-1-carboxylate To a stirred solution/mixture of tert-butyl 4-(bromomethylidene)piperidine-1-carboxylate (2.50 g, 9.052 mmol, 1 equiv) and bis(pinacolato)diboron (3.45 g, 13.578 mmol, 1.5 equiv) in 1,4-dioxane were added Pd(dppf)Cl2 (0.66 g, 0.905 mmol, 0.10 equiv) and KOAc (2.67 g, 27.157 mmol, 3 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 16 hours at 80 °C under nitrogen atmosphere. The reaction was quenched with Water at room temperature. The resulting mixture was extracted with EtOAc (3 x 30 mL). The combined organic layers were washed with brine (2 x 20 mL), dried over anhydrous Na2SC>4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluting with petroleum ether/EtOAc (5:1) to afford tert-butyl 4-[(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)methylidene]piperidine-1-carboxylate (1.2 g, 41%) as an off-white solid.
720 mg	With tris(dibenzylideneacetone)dipalladium⁽⁰⁾ chloroform complex; anhydrous potassium acetate; triphenylphosphine In 1,4-dioxane at 100℃; for 4h; Sealed tube; Inert atmosphere;	88 Preparation of ferf-butyl 4-[(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl methylenelpiperidine-l - carboxylate To a re-sealable tube was charged tert-butyl 4-(bromomethylene)piperidine-l-carboxylate (700 mg; 2.51 mmol), potassium acetate (620 mg; 6.27 mmol), bis(pinacolato)diboron (1040 mg; 4.01 mmol) and dioxane (20 mL) at room temperaure. Argon was bubbled in the reaction mixture for 10 minutes and triphenylphosphine (70 mg; 0.25 mmol) and tris(dibenzylideneacetone)dipalladium-chloroform adduct (160 mg; 0.15 mmol) were added. The tube was flushed with argon and sealed. The reaction mixture was then heated to 100 °C and stirred for 4 hours. After cooling to room temperature, the reaction mixture was filtered and the cake was washed with ethyl acetate. The filtrate was finally concentrated to dryness. The crude residue was then purified by column chromatography (silica gel; cyclohexane:ethylacetate; 1 :0 to 4: 1 ; v/v) to afford tert-butyl 4-[(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)methylene]piperidine-l- carboxylate (720 mg) as a light yellow solid. 'H-NMR (400 MHz, CDCI3) δ ppm: 5.17 (s, 1H), 3.42 - 3.48 (m,4H), 2.62 (m, 2H), 2.28 (m, 2H), 1.49 (s, 9H), 1.28 (s, 12H).
720 mg	With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; anhydrous potassium acetate; triphenylphosphine In 1,4-dioxane at 100℃; for 4h; Sealed tube; Inert atmosphere;	2.1-b Step 1-b: Preparation of ferf-butyl 4-r(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)methylene1piperidine- 1-carboxylate: A sealable tube was charged with teri-butyl 4-(bromomethylene)piperidine-l-carboxylate (700 mg; 2.51 mmol), potassium acetate (620 mg; 6.27 mmol), bis(pinacolato)diboron (1040 mg; 4.01 mmol) and dioxane (20 mL) at rt. Argon was bubbled in the reaction mixture for 10 min and triphenylphosphine (70 mg; 0.25 mmol) and Pd2dba3 (160 mg; 0.15 mmol) were added. The tube was flushed with argon and sealed. The reaction mixture was then heated to 100 °C and stirred for 4 h. After cooling to rt, the reaction mixture was filtered and the cake was washed with EA. The filtrate was finally concentrated to dryness. The residue was then purified by column chromatography (silica gel; c-Hex : EA; 1 :0 to 4:1 ; v/v) to afford teri-butyl 4-[(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)methylene]piperidine-l -carboxylate (720 mg) as a light yellow solid. (0713) 'H-NMR (400 MHz, CDCI3) δ ppm: 5.17 (s, 1H), 3.48 - 3.42 (m, 4H), 2.62 (m, 2H), 2.28 (m, 2H), 1.49 (s, 9H), 1.28 (s, 12H).
720 mg	With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; anhydrous potassium acetate; triphenylphosphine In 1,4-dioxane at 100℃; for 4h; Inert atmosphere; Sealed tube;	1.1-b Step 1-b: Preparation of ieri-butyl 4-r(4.4.5.5-tetramethyl-l.3.2-dioxaborolan-2-yl)methylene1piperidine- l-carboxylate A sealable tube was charged with ieri-butyl 4-(bromomethylene)piperidine-l-carboxylate (700 mg; 2.51 mmol), potassium acetate (620 mg; 6.27 mmol), bis(pinacolato)diboron (1 040 mg; 4.01 mmol) and dioxane (20 mL) at rt. Argon was bubbled in the reaction mixture for 10 min and triphenylphosphine (70 mg; 0.25 mmol) and Pd dba3 (160 mg; 0.15 mmol) were added. The tube was flushed with argon and sealed. The reaction mixture was then heated to 100 °C and stirred for 4 h. After cooling to rt, the reaction mixture was filtered and the cake was washed with EA. The filtrate was finally concentrated to dryness. The residue was then purified by column chromatography (silica gel; c-Hex : EA; 1 :0 to 4:1 ; v/v) to afford ieri-butyl 4-[(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)methylene]piperidine-l-carboxylate (720 mg) as a light yellow solid. (0253) ‘H-NMR (400 MHz, CDCI3) d ppm: 5.17 (s, 1H), 3.48 - 3.42 (m, 4H), 2.62 (m, 2H), 2.28 (m, 2H), 1.49 (s, 9H), 1.28 (s, 12H).

Reference： [1]Current Patent Assignee: CANCER THERAPEUTICS CRC PTY LTD - WO2017/153520, 2017, A1 Location in patent: Page/Page column 56
[2]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - WO2013/27001, 2013, A1 Location in patent: Page/Page column 69
[3]Current Patent Assignee: GOLDFINCH BIO INC - WO2021/67569, 2021, A1 Location in patent: Page/Page column 108-109
[4]Current Patent Assignee: GOLDFINCH BIO INC - WO2022/11274, 2022, A1 Location in patent: Page/Page column 184
[5]Current Patent Assignee: GOLDFINCH BIO INC - WO2022/11274, 2022, A1 Location in patent: Page/Page column 184
[6]Current Patent Assignee: BASILEA PHARMACEUTICA; BASILEA PHARM INT - WO2018/2220, 2018, A1 Location in patent: Page/Page column 123
[7]Current Patent Assignee: BASILEA PHARM INT - WO2019/72978, 2019, A1 Location in patent: Page/Page column 74
[8]Current Patent Assignee: BASILEA PHARM INT - WO2019/115709, 2019, A1 Location in patent: Page/Page column 24; 29

6
[ 79099-07-3 ]
[ 1425970-61-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: triphenylphosphine; carbon tetrabromide / acetonitrile / 2.25 h / 0 - 20 °C / Inert atmosphere 2.1: ammonia hydrochloride / tetrahydrofuran; methanol / 0.5 h / 0 °C / Inert atmosphere 2.2: 20 °C 3.1: triphenylphosphine; anhydrous potassium acetate; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾ / 1,4-dioxane / Reflux
	Multi-step reaction with 2 steps 1.1: lithium hexamethyldisilazane / tetrahydrofuran / 0.33 h / -15 °C 1.2: 2 h / -15 - 20 °C 2.1: triphenylphosphine; anhydrous potassium acetate; tris(dibenzylideneacetone)dipalladium⁽⁰⁾ chloroform complex / 1,4-dioxane / 4 h / 100 °C / Sealed tube; Inert atmosphere
	Multi-step reaction with 3 steps 1.1: triphenylphosphine / dichloromethane / 72 h / 0 - 20 °C / Inert atmosphere 2.1: ammonia hydrochloride / tetrahydrofuran; methanol / 0.5 h / 0 °C / Inert atmosphere 2.2: 4 h / 20 °C / Inert atmosphere 3.1: tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; anhydrous potassium acetate; triphenylphosphine / 1,4-dioxane / Inert atmosphere; Reflux

	Multi-step reaction with 2 steps 1.1: lithium hexamethyldisilazane / tetrahydrofuran / 0.33 h / -15 °C 1.2: 2 h / 20 °C 2.1: anhydrous potassium acetate; triphenylphosphine; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾ / 1,4-dioxane / 4 h / 100 °C / Sealed tube; Inert atmosphere
	Multi-step reaction with 2 steps 1.1: lithium hexamethyldisilazane / tetrahydrofuran / 0.33 h / -15 °C / Inert atmosphere 1.2: 2 h / 18 - 25 °C / Inert atmosphere 2.1: anhydrous potassium acetate; triphenylphosphine; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾ / 1,4-dioxane / 4 h / 100 °C / Inert atmosphere; Sealed tube
	Multi-step reaction with 2 steps 1.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -20 °C 1.2: 16 h / -20 °C 2.1: anhydrous potassium acetate; palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride / 1,4-dioxane / 16 h / 80 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -20 °C / Inert atmosphere 1.2: 16 h / -20 - 20 °C / Inert atmosphere 2.1: palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; anhydrous potassium acetate / 1,4-dioxane / 16 h / 80 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: CANCER THERAPEUTICS CRC PTY LTD - WO2017/153520, 2017, A1
[2]Current Patent Assignee: BASILEA PHARMACEUTICA; BASILEA PHARM INT - WO2018/2220, 2018, A1
[3]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - WO2013/27001, 2013, A1
[4]Current Patent Assignee: BASILEA PHARM INT - WO2019/72978, 2019, A1
[5]Current Patent Assignee: BASILEA PHARM INT - WO2019/115709, 2019, A1
[6]Current Patent Assignee: GOLDFINCH BIO INC - WO2021/67569, 2021, A1
[7]Current Patent Assignee: GOLDFINCH BIO INC - WO2022/11274, 2022, A1

7
[ 1425970-61-1 ]
4-((2-(butylamino)-5-(5-chloropyridin-2-yl)pyrimidine-4-yl)amino)cyclohexanol [ No CAS ]
tert-butyl 4-((6-(2-(butylamino)-4-((4-hydroxycyclohexyl)amino)pyrimidin-5-yl)pyridin-3-yl)methylene)piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate In water; acetonitrile at 90℃; Inert atmosphere;	13 A mixture of SPhos (165 mg, 0.2 mol %), Pd(OAc)2 (45 mg, 0.4 mmol), K3P04 (850 mg, 4.0 mmol, 2.0 equiv), 4-((2-(butylammo)-5-(5-chloropyridm-2-yl)pyridin-4-yl)amino)cyclohexanol (752 mg, 2.0 mmol, 1 equiv, this compound could be prepared by procedure D in table 5), tert-butyl 4-((4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)methylene)piperidine-l-carboxylate (776 mg, 2.4 nunol, 2.0 equiv), CCN (30 mL) and water (20 mL) in a 50 mL flask was stirred under Ar atmosphere at 90°C overnight. The resulting mixture was passed through a pad of Celite and the pad was washed several times with EtOAc. The filtrate was washed with brine, dried (Na2S04), and concentrated. The crude material was purified using ISCO to provide the desired product tert-bu 4- ((6-(2-(butylamino)-4-((4-hydroxycyclohexyl)amino)pyrimidin-5 -yl)pyridin-3 -yl)methylene) piperidine-l-carboxylate. A solution of crude te -butyl 4-((6-(2-(butylamino)-4-((4- hydroxycyclohexyl)ammo)pyrimidm-5-yl)pyridm-3-yl)methylene)piperidine-l-carboxylate (536 mg, 1 mmol) in MeOH (30 mL) was subjected to H-Cube at 80°C and 100 bar. The solvent was removed and the crude product was treated with a 3.0 N HCl solution in MeOH (6.0 mL) overnight. The solvent was removed and the residue was purified using HPLC to afford pure the desired product frai-4-((2-(burylamino)-5-(5-(piperidm^ (1102) l-ol (202 mg, 37%) (UNC4335A). 1H NMR (400 MHz, CD3OD) δ 8.53 (s, 1H), 8.28 (s, 1H), 7.89 (s, 2H), 4.20-4.10 (m, 1H), 3.69-3.60 (m, 1H), 3.55-3.42 (m, 2H), 3.42-3.35 (m, 2H), 3.01-2.92 (m, 2H), 2.73 (d, J= 8.0 Hz, 2H), 2.20-2.12 (m, 2H), 2.06-1.94 (m, 3H), 1.93-1.86 (m, 2H), 1.72-1.63 (m, 2H), 1.58-1.39 (m, 8H), 1.00 (t, J= 8.0 Hz, 3H).MS m/z 439.62 [M+H]+.

Reference： [1]Current Patent Assignee: UNIVERSITY OF NORTH CAROLINA SYSTEM - WO2015/157127, 2015, A1 Location in patent: Page/Page column 254-255

8
[ 1425970-61-1 ]
trans-4-((2-(butylamino)-5-(5-(piperidin-4-ylmethyl)pyridin-2-yl)pyrimidin-4-yl)amino)cyclohexan-1-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: palladium diacetate; potassium phosphate; dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane / water; acetonitrile / 90 °C / Inert atmosphere 2: hydrogen / methanol / 80 °C / 75007.5 Torr 3: hydrogenchloride / methanol

Reference： [1]Current Patent Assignee: UNIVERSITY OF NORTH CAROLINA SYSTEM - WO2015/157127, 2015, A1

9
[ 1425970-61-1 ]
C₂₈H₄₄N₆O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: palladium diacetate; potassium phosphate; dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane / water; acetonitrile / 90 °C / Inert atmosphere 2: hydrogen / methanol / 80 °C / 75007.5 Torr 3: hydrogenchloride / methanol 4: N-ethyl-N,N-diisopropylamine / isopropyl alcohol / 110 °C

Reference： [1]Current Patent Assignee: UNIVERSITY OF NORTH CAROLINA SYSTEM - WO2015/157127, 2015, A1

10
[ 1425970-61-1 ]
C₃₀H₄₆N₆O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: palladium diacetate; potassium phosphate; dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane / water; acetonitrile / 90 °C / Inert atmosphere 2: hydrogen / methanol / 80 °C / 75007.5 Torr

Reference： [1]Current Patent Assignee: UNIVERSITY OF NORTH CAROLINA SYSTEM - WO2015/157127, 2015, A1

11
[ 1425970-61-1 ]
ethyl 2-bromo-5-ethoxyisonicotinate [ No CAS ]
ethyl 2-((1-(tert-butoxycarbonyl)piperidin-4-ylidene)methyl)-5-ethoxyisonicotinate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate In 1,4-dioxane; water at 80℃;	viii.d (d) Ethyl 2-((1 -(tert-butoxycarbonyl)piperidin-4-ylidene)methyl)-5-ethoxyisonicotinate (123) To a solution of tert-butyl 4-((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene) piperidine-1-carboxylate 122 (1.5 g, 4.64 mmol) and ethyl 2-bromo-5-ethoxyisonicotinate 119 (1 .53 g, 5.57 mmol) in 1,4 -dioxane (20 mL) was added a saturated aqueous Na2003 solution (4 mL) and Pd(dppf)C12 (680 mg, 0.928 mmol). The mixture was heated at 80 00 overnight then filtered through Celite and the filtrate concentrated. The residue obtained waspartitioned between DCM (20 mL) and water (20 mL) and the aqueous phase extracted withDCM (3 x 10 mL). The combined organic extracts were washed with a saturated aqueousNaHCO3 solution (3 x 10 mL), brine (3 x 10 mL), dried (Na2SO4), filtered and concentrated.The residue obtained was purified by column chromatography (EtOAc/petroleum ether=1/5v/v) to give the title compound (1.1 g, 60%) as an off-white solid. 1H NMR (400MHz, ODd3)68.36 (s, 1H), 7.43 (s, 1H), 6.33 (s, 1H), 4.40-4.35 (q, J= 7.2 Hz, 2H), 4.24-4.18 (q, J= 6.8Hz, 2H), 3.51 (t, J = 6.0 Hz, 2H), 3.44 (t, J = 6.0 Hz, 2H), 2.79 (t, J = 5.6 Hz, 2H), 2.35 (t, J =5.6 Hz, 2H), 1.48-1.44 (m, 12H), 1.38 (t, J = 7.2 Hz, 3H); LCMS RT 3.17 mm; m/z 391.2[M+H]

Reference： [1]Current Patent Assignee: CANCER THERAPEUTICS CRC PTY LTD - WO2017/153520, 2017, A1 Location in patent: Page/Page column 56

12
[ 1425970-61-1 ]
ethyl 2-((1-(tert-butoxycarbonyl)piperidin-4-yl)methyl)-5-ethoxyisonicotinate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: sodium carbonate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane; water / 80 °C 2: palladium 10% on activated carbon; hydrogen / methanol / 20 °C

Reference： [1]Current Patent Assignee: CANCER THERAPEUTICS CRC PTY LTD - WO2017/153520, 2017, A1

13
[ 1425970-61-1 ]
ethyl 5-ethoxy-2-(piperidin-4-ylmethyl)isonicotinate dihydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: sodium carbonate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane; water / 80 °C 2: palladium 10% on activated carbon; hydrogen / methanol / 20 °C 3: hydrogenchloride / diethyl ether; methanol / 2 h / 20 °C

Reference： [1]Current Patent Assignee: CANCER THERAPEUTICS CRC PTY LTD - WO2017/153520, 2017, A1

14
[ 1425970-61-1 ]
2-((1-acetylpiperidin-4-yl)methyl)-5-ethoxyisonicotinic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: sodium carbonate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane; water / 80 °C 2: palladium 10% on activated carbon; hydrogen / methanol / 20 °C 3: hydrogenchloride / diethyl ether; methanol / 2 h / 20 °C 4: triethylamine / dichloromethane / 20 °C 5: lithium hydroxide monohydrate; water / tetrahydrofuran; methanol / 20 °C

Reference： [1]Current Patent Assignee: CANCER THERAPEUTICS CRC PTY LTD - WO2017/153520, 2017, A1

15
[ 1425970-61-1 ]
ethyl 2-((1-acetylpiperidin-4-yl)methyl)-5-ethoxyisonicotinate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: sodium carbonate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane; water / 80 °C 2: palladium 10% on activated carbon; hydrogen / methanol / 20 °C 3: hydrogenchloride / diethyl ether; methanol / 2 h / 20 °C 4: triethylamine / dichloromethane / 20 °C

Reference： [1]Current Patent Assignee: CANCER THERAPEUTICS CRC PTY LTD - WO2017/153520, 2017, A1

16
[ 1425970-61-1 ]
3-(4-chloro-1-oxo-1H-pyrrolo[3,4-c]pyridin-2(3H)-yl)piperidine-2,6-dione [ No CAS ]
tert-butyl 4-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-4-yl)methylene)piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
34.5%	With methanesulfonic acid(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II); caesium carbonate; XPhos In tetrahydrofuran; water at 60℃; for 5h; Inert atmosphere;	Intermediate 34-2. Preparation of tert-Butyl 4-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-4-yl)methylene)piperidine-1-carboxylate Brought 3-(4-chloro-1-oxo-1H-pyrrolo[3,4-c]pyridin-2(3H)-yl)piperidine-2,6-dione (30- 2) (120 mg, 0.4290 mmol) , tert-butyl 4-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)methylene)piperidine-1-carboxylate (34-1) (277 mg, 0.858 mmol) , cesium carbonate (417 mg, 1.28 mmol) , dicyclohexyl(2',4',6'-triisopropyl-[1,1'-biphenyl]-2-yl)phosphine (30.6 mg, 0.06435 mmol) and XPhos G3 (54.4 mg, 0.06435 mmol) up in thf (2.86 mL ) / water (300 ul ) under Ar. Stirred at 60°C for 5 hours. Concentrated off THF and concentrated onto celite from toluene. Purified by isco 0-15% MeOH/DCM to give tert-butyl 4-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3- dihydro-1H-pyrrolo[3,4-c]pyridin-4-yl)methylene)piperidine-1-carboxylate (34-2) (65.0 mg, 0.1475 mmol, 34.5 %) as an off-white solid. LCMS (ES+): m/z= 441 [M + H]+

Reference： [1]Current Patent Assignee: C4 THERAPEUTICS INC - WO2017/197056, 2017, A1 Location in patent: Page/Page column 379

17
[ 1425970-61-1 ]
3-fluoro-4-(4-piperidylidenemethyl)benzaldehyde trifluoroacetic acid salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: potassium carbonate; tetrakis(triphenylphosphine) palladium⁽⁰⁾ / 1,4-dioxane; water / 3 h / 95 °C / Sealed tube; Inert atmosphere 2: dichloromethane

Reference： [1]Current Patent Assignee: BASILEA PHARMACEUTICA; BASILEA PHARM INT - WO2018/2220, 2018, A1

18
[ 1425970-61-1 ]
[ 133059-43-5 ]
tert-butyl 4-[(2-fluoro-4-formylphenyl)methylene]piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
400 mg	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium carbonate In 1,4-dioxane; water at 95℃; for 3h; Sealed tube; Inert atmosphere;	88 Preparation of ferf-butyl 4-[(2-fluoro-4-formyl-phenyl)methylenelpiperidine-l-carboxylate In a re-sealable tube was charged tert-butyl 4-[(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2- yl)methylene]piperidine-l-carboxylate (720 mg; 2.01 mmol), 4-bromo-3-fluoro-benzaldehyde (500 mg; 2.41 mmol) [133059-46-5], potassium carbonate (800 mg; 5.73 mmol), water (4 mL) and dioxane (20 mL) at room temperature. Argon was bubbled into the mixture for 10 minutes and tetrakis(triphenylphosphine)palladium(0) (140 mg; 0.12 mmol) was added. Argon was bubbled for additional 5 minutes and the tube was sealed. The reaction mixture was then heated to 95 °C and stirred for 3 hours. After cooling to room temperature, ethyl acetate and water were added and the organic layer was separated, washed with brine, dried over MgSO i, filtered and concentrated to dryness. The crude residue was then purified by column chromatography (silica gel; cyclohexane:ethylacetate; 1 :0 to 65:35; v/v) to afford tert-butyl 4-[(2-fluoro-4-formyl-phenyl)methylene]piperidine-l-carboxylate (400 mg) as a light yellow solid. 'H-NMR (400 MHz, CDC13) δ ppm: 9.98 (s, 1H), 7.54 - 7.56 (m, 2H), 7.36 - 7.40 (m, 1H), 6.34 (s, 1H), 3.56 (m, 2H), 3.46 (m, 2H), 2.37 - 2.43 (m, 4H), 1.50 (s, 9H).

Reference： [1]Current Patent Assignee: BASILEA PHARMACEUTICA; BASILEA PHARM INT - WO2018/2220, 2018, A1 Location in patent: Page/Page column 123-124

19
[ 1425970-61-1 ]
[ 57054-92-9 ]
tert-butyl 4-((2-chloro-4-methoxypyrimidin-5-yl)methylene)piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 80℃; for 24h;Inert atmosphere; Sealed tube;	Prepared according to General Procedure 4 using <strong>[57054-92-9]5-bromo-2-chloro-4-methoxypyrimidine</strong> (259 mg, 1 .16 mmol), fe/f-butyl 4-((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)piperidine-1- carboxylate (PCT Int. Appl., 2013027001 , 28 Feb 2013) (450 mg, 1.39 mmol), Pd(PPh3)4 (67 mg, 0.058 mmol), sodium carbonate (2 M in water, 1.16 mL, 2.32 mmol) and DME (5.8 mL). The mixture was heated at 80 C for 24 h to give the title compound (334 mg, 85%). LCMS (Method B): RT = 1.80 min, m/z = 340, 342 [M+H]+. 1 H NMR (300 MHz, CDCI3): 5 8.10 (s, 1 H), 6.07 (s, 1 H), 4.04 (s, 3H), 3.52 (t, 2H), 3.42 (t, 2H), 2.37 (t, 2H), 2.32 (t, 2H), 1.48 (s, 9H).

Reference： [1]Patent: WO2018/20242,2018,A1 .Location in patent: Page/Page column 115; 116

20
[ 1425970-61-1 ]
(R)-1-(4-((2-chloro-4-methoxypyrimidin-5-yl)methylene)piperidin-1-yl)-3-phenylbutan-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate / water; 1,2-dimethoxyethane / 24 h / 80 °C / Inert atmosphere; Sealed tube 2: dichloromethane / 2 h / 20 °C 3: dmap; N-ethyl-N,N-diisopropylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 24 h / 20 °C

Reference： [1]Current Patent Assignee: THE MCCLAY FOUNDATION - WO2018/20242, 2018, A1

21
[ 1425970-61-1 ]
C₁₁H₁₄ClN₃O*C₂HF₃O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate / water; 1,2-dimethoxyethane / 24 h / 80 °C / Inert atmosphere; Sealed tube 2: dichloromethane / 2 h / 20 °C

Reference： [1]Current Patent Assignee: THE MCCLAY FOUNDATION - WO2018/20242, 2018, A1

22
[ 1425970-61-1 ]
(R)-1-(4-((4-methoxy-2-phenylpyrimidin-5-yl)methylene)piperidin-1-yl)-3-phenylbutan-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate / water; 1,2-dimethoxyethane / 24 h / 80 °C / Inert atmosphere; Sealed tube 2: dichloromethane / 2 h / 20 °C 3: dmap; N-ethyl-N,N-diisopropylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 24 h / 20 °C 4: tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate / water; 1,2-dimethoxyethane / 24 h / 75 °C / Inert atmosphere; Sealed tube

Reference： [1]Current Patent Assignee: THE MCCLAY FOUNDATION - WO2018/20242, 2018, A1

23
[ 1425970-61-1 ]
(3R)-1-(2-(4-methoxy-2-phenylpyrimidin-5-yl)-1-oxa-6-azaspiro[2.5]octan-6-yl)-3-phenylbutan-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate / water; 1,2-dimethoxyethane / 24 h / 80 °C / Inert atmosphere; Sealed tube 2: dichloromethane / 2 h / 20 °C 3: dmap; N-ethyl-N,N-diisopropylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 24 h / 20 °C 4: tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate / water; 1,2-dimethoxyethane / 24 h / 75 °C / Inert atmosphere; Sealed tube 5: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 1.5 h

Reference： [1]Current Patent Assignee: THE MCCLAY FOUNDATION - WO2018/20242, 2018, A1

24
[ 1425970-61-1 ]
(R)-1-(4-hydroxy-4-((4-methoxy-2-phenylpyrimidin-5-yl)methyl)piperidin-1-yl)-3-phenylbutan-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate / water; 1,2-dimethoxyethane / 24 h / 80 °C / Inert atmosphere; Sealed tube 2: dichloromethane / 2 h / 20 °C 3: dmap; N-ethyl-N,N-diisopropylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 24 h / 20 °C 4: tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate / water; 1,2-dimethoxyethane / 24 h / 75 °C / Inert atmosphere; Sealed tube 5: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 1.5 h 6: palladium 10% on activated carbon; hydrogen / methanol / 20 - 40 °C / 37503.8 Torr

Reference： [1]Current Patent Assignee: THE MCCLAY FOUNDATION - WO2018/20242, 2018, A1

25
[ 1425970-61-1 ]
(R)-5-((4-hydroxy-1-(3-phenylbutanoyl)piperidin-4-yl)methyl)-2-phenylpyrimidin-4(3H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate / water; 1,2-dimethoxyethane / 24 h / 80 °C / Inert atmosphere; Sealed tube 2: dichloromethane / 2 h / 20 °C 3: dmap; N-ethyl-N,N-diisopropylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 24 h / 20 °C 4: tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate / water; 1,2-dimethoxyethane / 24 h / 75 °C / Inert atmosphere; Sealed tube 5: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 1.5 h 6: palladium 10% on activated carbon; hydrogen / methanol / 20 - 40 °C / 37503.8 Torr 7: sodium iodide; chloro-trimethyl-silane / acetonitrile / 15 h / 80 °C

Reference： [1]Current Patent Assignee: THE MCCLAY FOUNDATION - WO2018/20242, 2018, A1

26
3-bromo-4H-pyrido[1,2-a]pyrimidin-4-one [ No CAS ]
[ 1425970-61-1 ]
tert-butyl 4-((4-oxo-4H-pyrido[1,2-a]pyrimidin-3-yl)methylene)piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate In 1,2-dimethoxyethane; water at 80℃; for 72h; Inert atmosphere;	101.1 General procedure 5: Suzuki coupling General procedure: A reaction vial was charged with a mixture of the bromide (1 equiv.), the organoboron reagent (1-3 equiv.), a Pd catalyst (0.05-0.1 equiv.) and an inorganic base (2-5 equiv.) in 1 ,4-dioxane/water or DME/water and the 02 was removed by evacuating and refilling with N2 three times before the reaction tube was sealed. The reaction was heated under the indicated conditions for the indicated time before being cooled to RT and saturated NH4CI(aq) was added. The mixture was then extracted with DCM (x3) using a Biotage phase separator. The combined organic phases were concentrated and the residue purified by flash chromatography (Biotage KP-Sil and KP-NH, 0-100% EtOAc in cyclohexane or PE, then 0- 30% MeOH in EtOAc) to give the product.

Reference： [1]Current Patent Assignee: THE MCCLAY FOUNDATION; ROCHE HOLDING AG; O DOWD COLIN - WO2018/73602, 2018, A1 Location in patent: Page/Page column 55; 56; 141

27
3-bromo-4H-pyrido[1,2-a]pyrimidin-4-one [ No CAS ]
[ 1425970-61-1 ]
tert-butyl 4-hydroxy-4-(hydroxy(4-oxo-4H-pyrido[1,2-a]pyrimidin-3-yl)methyl)piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: sodium carbonate; tetrakis(triphenylphosphine) palladium⁽⁰⁾ / 1,2-dimethoxyethane; water / 72 h / 80 °C / Inert atmosphere 2: potassium osmate(VI) dihydrate; 4-methylmorpholine N-oxide / dichloromethane; water / 24 h

Reference： [1]Current Patent Assignee: THE MCCLAY FOUNDATION; ROCHE HOLDING AG; O DOWD COLIN - WO2018/73602, 2018, A1

28
[ 1425970-61-1 ]
3-bromo-9-phenyl-4H-pyrido[1,2-a]pyrimidin-4-one [ No CAS ]
tert-butyl 4-((4-oxo-9-phenyl-4H-pyrido[1,2-a]pyrimidin-3-yl)methylene)piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate In 1,2-dimethoxyethane; water at 100℃; for 72h; Inert atmosphere;	19.2 General procedure 5: Suzuki coupling General procedure: A reaction vial was charged with a mixture of the bromide (1 equiv.), the organoboron reagent (1-3 equiv.), a Pd catalyst (0.05-0.1 equiv.) and an inorganic base (2-5 equiv.) in 1 ,4-dioxane/water or DME/water and the 02 was removed by evacuating and refilling with N2 three times before the reaction tube was sealed. The reaction was heated under the indicated conditions for the indicated time before being cooled to RT and saturated NH4CI(aq) was added. The mixture was then extracted with DCM (x3) using a Biotage phase separator. The combined organic phases were concentrated and the residue purified by flash chromatography (Biotage KP-Sil and KP-NH, 0-100% EtOAc in cyclohexane or PE, then 0- 30% MeOH in EtOAc) to give the product.

Reference： [1]Current Patent Assignee: THE MCCLAY FOUNDATION; ROCHE HOLDING AG; O DOWD COLIN - WO2018/73602, 2018, A1 Location in patent: Page/Page column 55; 56; 71

29
[ 883546-16-5 ]
[ 1425970-61-1 ]
tert-butyl 4-[(4-chloro-2,6-difluorophenyl)methylene]piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
4000 mg	With potassium phosphate; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; XPhos In 1,4-dioxane; water at 100℃; for 2h; Inert atmosphere;	2.1-c Step 1-c: Preparation of fer/-butyl 4-r(4-chloro-2,6-difluorophenyl)methylene1piperidine-l-carboxylate: Under argon atmosphere, a mixture of X-Phos (745 mg; 1.53 mmol), 2-bromo-5-chloro-l,3-difluoro- benzene (3518 mg; 15.31 mmol), teri-butyl 4-[(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)methylene]- piperidine-l-carboxylate (5500 mg;, 15.31 mmol), Pd2dba3 (708 mg; 0.76 mmol) and K3PO4 (4975 mg; 22.97 mmol) in a mixture of H20 (5 mL) and dioxane (100 mL) was heated to 100 °C and stirred for 2 h. After cooling down to rt, H20 and EA were added. The organic layer was separated, washed with brine, dried over MgSO i, filtered and concentrated to dryness. The residue was purified by column chromatography (silica gel; PE : EA; 40: 1 ; v/v) to afford feri-butyl 4-[(4-chloro-2,6-difluorophenyl)- methylene]piperidine-l-carboxylate (4000 mg) as a light yellow solid. (0715) MS m/z (+ESI): 288.0, 290.0 [M-i-Bu+H]+. (0716) 'H-NMR (400 MHz, CDC13) δ ppm: 6.96 - 6.91 (m, 2H), 5.93 (s, 1H), 3.53 (t, J= 5.6 Hz, 2H), 3.43 (t, J = 5.6 Hz, 2H), 2.38 (t, J= 5.6 Hz, 2H), 2.13 (t, J= 5.6 Hz, 2H), 1.48 (s, 9H).

Reference： [1]Current Patent Assignee: BASILEA PHARM INT - WO2019/72978, 2019, A1 Location in patent: Page/Page column 74-75

30
[ 1425970-61-1 ]
4-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene)-piperidine hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	With hydrogenchloride In 1,4-dioxane for 2h;

Reference： [1]Kovalenko, Maksym; Yarmoliuk, Dmytro V.; Serhiichuk, Dmytro; Chernenko, Daria; Smyrnov, Vladyslav; Breslavskyi, Artur; Hryshchuk, Oleksandr V.; Kleban, Ihor; Rassukana, Yuliya; Tymtsunik, Andriy V.; Tolmachev, Andrey A.; Kuchkovska, Yuliya O.; Grygorenko, Oleksandr O. [European Journal of Organic Chemistry, 2019, vol. 2019, # 33, p. 5624 - 5635]

31
[ 1425970-61-1 ]
tert-butyl 4-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-methyl)piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With palladium 10% on activated carbon; hydrogen In tetrahydrofuran at 20℃;

Reference： [1]Kovalenko, Maksym; Yarmoliuk, Dmytro V.; Serhiichuk, Dmytro; Chernenko, Daria; Smyrnov, Vladyslav; Breslavskyi, Artur; Hryshchuk, Oleksandr V.; Kleban, Ihor; Rassukana, Yuliya; Tymtsunik, Andriy V.; Tolmachev, Andrey A.; Kuchkovska, Yuliya O.; Grygorenko, Oleksandr O. [European Journal of Organic Chemistry, 2019, vol. 2019, # 33, p. 5624 - 5635]

32
[ 79099-07-3 ]
[ 78782-17-9 ]
[ 1425970-61-1 ]

Yield	Reaction Conditions	Operation in experiment
80%	Stage #1: 4,4,5,5-tetramethyl-2-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl]-1,3,2-dioxaborolane With 2,2,6,6-tetramethyl-piperidine; n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.05h; Stage #2: N-tert-butyloxycarbonylpiperidin-4-one In tetrahydrofuran; hexane at -78 - 20℃;

Reference： [1]Kovalenko, Maksym; Yarmoliuk, Dmytro V.; Serhiichuk, Dmytro; Chernenko, Daria; Smyrnov, Vladyslav; Breslavskyi, Artur; Hryshchuk, Oleksandr V.; Kleban, Ihor; Rassukana, Yuliya; Tymtsunik, Andriy V.; Tolmachev, Andrey A.; Kuchkovska, Yuliya O.; Grygorenko, Oleksandr O. [European Journal of Organic Chemistry, 2019, vol. 2019, # 33, p. 5624 - 5635]

33
[ 1425970-61-1 ]
4-[(4-chloro-2-fluorophenyl)methylene]piperidine hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; XPhos; potassium phosphate / 1,4-dioxane; water / 2 h / 100 °C / Inert atmosphere 2: hydrogenchloride / ethyl acetate / 2 h / Inert atmosphere

Reference： [1]Current Patent Assignee: BASILEA PHARM INT - WO2019/115709, 2019, A1

34
[ 1425970-61-1 ]
4-[(4-chloro-2-fluorophenyl)methylene]-N-(2,3-dimethyl-4-pyridyl)piperidine-1-carboxamide trifluoroacetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; XPhos; potassium phosphate / 1,4-dioxane; water / 2 h / 100 °C / Inert atmosphere 2.1: hydrogenchloride / ethyl acetate / 2 h / Inert atmosphere 3.1: dmap; triethylamine / tetrahydrofuran / 2 h / 0 - 25 °C / Inert atmosphere 3.2: 16 h / Inert atmosphere

Reference： [1]Current Patent Assignee: BASILEA PHARM INT - WO2019/115709, 2019, A1

35
[ 1425970-61-1 ]
4-[(4-chloro-2-fluorophenyl)methylene]-N-(3-methoxy-2-methyl-4-pyridyl)piperidine-1-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; XPhos; potassium phosphate / 1,4-dioxane; water / 2 h / 100 °C / Inert atmosphere 2.1: hydrogenchloride / ethyl acetate / 2 h / Inert atmosphere 3.1: triethylamine / acetonitrile / 24 h / -10 - 25 °C / Inert atmosphere 3.2: 24 h / 70 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: BASILEA PHARM INT - WO2019/115709, 2019, A1

36
[ 1996-29-8 ]
[ 1425970-61-1 ]
tert-butyl 4-[(4-chloro-2-fluorophenyl)methylene]piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
4000 mg	With potassium phosphate; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; XPhos In 1,4-dioxane; water at 100℃; for 2h; Inert atmosphere;	1.1-c Step 1-c: Preparation of ieri-butyl 4-r(4-chloro-2-fluoro-phenyl)methylene1piperidine-l -carboxylate Under argon atmosphere, a mixture of X-Phos (750 mg; 1.53 mmol), l-bromo-4-chloro-2-fluoro-benzene (1.93 mL; 15.31 mmol), ieri-butyl 4-[(4, 4,5, 5-tetramethyl-l, 3, 2-dioxaborolan-2-yl)methylene]piperidine- 1 -carboxylate (5 500 mg;, 15.31 mmol), Pd dba3 (708 mg; 0.76 mmol) and K3P04 (4 975 mg; 22.97 mmol) in a mixture of H20 (5 mL) and dioxane (100 mL) was heated to 100 °C and stirred for 2 h. After cooling down to rt, H20 and EA were added. The organic layer was separated, washed with brine, dried over MgS04, filtered and concentrated to dryness. The residue was purified by column chromatography (silica gel;PE: EA; 30:1 ; v/v) to afford feri-butyl 4-[(4-chloro-2-fluoro-phenyl)methylene]piperidine-l- carboxylate (4 000 mg) as a white solid. (0255) MS xn/z (+ESI): 311.1, 313.1 [M-/-Bu+HCOOH]+. (0256) ‘H-NMR (400 MHz, CDC13) d ppm: 7.10 - 7.06 (m, 3H), 6.20 (s, 1H), 3.51 (t, J= 5.6 Hz, 2H), 3.41 (t, J = 5.6 Hz, 2H), 2.36 - 2.30 (m, 4H), 1.48 (s, 9H).

Reference： [1]Current Patent Assignee: BASILEA PHARM INT - WO2019/115709, 2019, A1 Location in patent: Page/Page column 24; 29-30

37
[ 1425970-61-1 ]
3-(8-(bis(4-methoxybenzyl)amino)-2-(2-chloro-6-fluorobenzyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-2-fluorobenzonitrile [ No CAS ]
tert-butyl 4-(2-((8-(bis(4-methoxybenzyl)amino)-6-(3-cyano-2-fluorophenyl)-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)methyl)-3-fluorobenzylidene)piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphino-(2′-aminobiphenyl-2-yl)(chloro)palladium; potassium carbonate In 1,4-dioxane; water at 120℃; for 1.53333h; Inert atmosphere;	91.1 Step 1: tert-butyl 4-(2-((8-(bis(4-methoxybenzyl)amino)-6-(3-cyano-2-fiuorophenyl,)- [1,2, 4]triazolo[1 , 5-a]pyrazin-2-yl)methyl)-3-fiuorobenzylidene,)pzperidine-1- carboxylate A mixture of 3 -(8-(bis(4-methoxybenzyl)amino)-2-(2-chloro-6-fluorobenzyl)-[1 ,2,4jtriazolo [1,5 -ajpyrazin-6-yl)-2-fluorobenzonitrile (193 mg, 0.303 mmol) (fromExample 99, step 4), XPhos Pd G2 (23.84 mg, 0.030 mmol), potassium phosphate (193 mg, 0.909 mmol) and tert-butyl 4-((4,4,5,5 -tetramethyl- 1 ,3,2-dioxaborolan-2- yl)methylene)piperidine-1-carboxylate (98.1 mg, 0.303 mmol) in 1,4-dioxane (2.75 mL)/Water (0.550 mL) in a 40 mL vial was flushed with nitrogen for ca 2 mm and heated at 120 °C for 3 h. After cooling to room temp, the mixture was diluted with water and extracted with DCM (x3). The combined organic extracts were dried (anhyd. Na2SO4), concentrated under reduced pressure, and purified by Biotage Isolera (with 50 g silica gel column) eluting with 0-100% EtOAc/Hexane to give theproduct. LCMS calculated for C46H46F2N7O4 (M+H): m/z = 798.4; found: 798.4.

Reference： [1]Current Patent Assignee: INCYTE CORP - WO2020/10197, 2020, A1 Location in patent: Page/Page column 219-220

38
[ 1425970-61-1 ]
potassium [6-(tert-butoxycarbonyl)-2,2-difluoro-6-azaspiro-[2.5]octan-1-yl]trifluoroborate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: methanol 2: sodium iodide / tetrahydrofuran / 0.5 h / Reflux

Reference： [1]Grygorenko, Oleksandr O.; Hryshchuk, Oleksandr V.; Kuchkovska, Yuliya O.; Tymtsunik, Andriy V.; Varenyk, Anatolii O.; Yurov, Yevhen [European Journal of Organic Chemistry, 2020, vol. 2020, # 15, p. 2217 - 2224]

39
potassium hydrogen difluoride [ No CAS ]
[ 1425970-61-1 ]
potassium [1-(tert-butoxycarbonyl)piperidin-4-ylidene]methyl}trifluoroborate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	In methanol

Reference： [1]Grygorenko, Oleksandr O.; Hryshchuk, Oleksandr V.; Kuchkovska, Yuliya O.; Tymtsunik, Andriy V.; Varenyk, Anatolii O.; Yurov, Yevhen [European Journal of Organic Chemistry, 2020, vol. 2020, # 15, p. 2217 - 2224]

40
[ 1425970-61-1 ]
5-cyano-N-(3-iodo-1H-indazol-5-yl)-3,4-dimethylpicolinamide [ No CAS ]
tert-butyl 4-((5-(5-cyano-3,4-dimethylpicolinamido)-1H-indazol-3-yl)methylene)piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II); potassium acetate In ethanol; water at 90℃; for 12h; Inert atmosphere;	259.3 Step 3: tert-butyl 4-((5-(5-Cyano-3,4-dimethylpicolinamido)-1H-indazol-3- yl)methylene)piperidine-1-carboxylate To a solution of 5-cyano-N-(3-iodo-1H-indazol-5-yl)-3,4-dimethylpicolinamide (64.54 mg, 154.69 umol) in EtOH (4 mL) and H2O (1 mL) was added KOAc (75.90 mg, 773.43 umol), Pd(Amphos)Cl2 (10.95 mg, 15.47 umol) and tert-butyl 4-((4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)methylene)piperidine-1-carboxylate (50 mg, 154.69 umol) at 20 °C. Then the reaction mixture was stirred at 90 °C for 12 hrs under N2. The reaction mixture was concentrated and purified by preparative HPLC using Method AV to afford the title compound (28.8 mg, 38%) as a pale yellow solid.1H NMR (400 MHz, DMSO-d6) d 12.99 (s, 1H), 10.66 (s, 1H), 8.88 (s, 1H), 8.31 (s, 1H), 7.59 - 7.47 (m, 2H), 6.52 (s, 1H), 3.49 - 3.38 (m, 4H), 2.83 (br s, 2H), 2.55 (s, 3H), 2.44 (s, 3H), 2.42 - 2.38 (m, 2H), 1.43 (s, 9H). MS-ESI (m/z) calc’d for C27H31N6O3 [M+H]+: 487.2 Found 487.3.

Reference： [1]Current Patent Assignee: E SCAPE BIO - WO2021/7477, 2021, A1 Location in patent: Page/Page column 411; 412; 143

41
[ 1425970-61-1 ]
2,7-dichloro-1,6-naphthyridine [ No CAS ]
tert-butyl 4-[(7-chloro-1,6-naphthyridin-2-yl)methylidene]piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis-(triphenylphosphine)-palladium; anhydrous sodium carbonate In water monomer at 100℃; for 40h; Inert atmosphere;	18 Tert-butyl 4-[(7-chloro-1,6-naphthyridin-2-yl)methylidene]piperidine-1-carboxylate. A mixture of 2,7-dichloro-1,6-naphthyridine (1.98 g, 9.948 mmol, 1 equiv.), tert-butyl 4-[(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)methylidene]piperidine-1-carboxylate (6.43 g, 19.896 mmol, 2 equiv.), Pd(PPh3)4 (2.30 g, 1.990 mmol, 0.20 equiv.) in dioxane (100 mL) and Na2CO3 (2.11 g, 19.896 mmol, 2 equiv.) in H2O (10 mL, 555.084 mmol, 55.80 equiv.) and this resulting mixture was stirred at 100 C for 40 hours under N2 atmosphere. The reaction mixture was cooled down to room temperature and added H2O (100 mL). The resulting mixture was extracted with EtOAc (3 x 100 mL). The combined organic layers were washed with brine (2x100 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure to give the residue, which was purified by silica gel column chromatography, eluted with PE:EtOAc (4:1 to 2:1) to afford tert-butyl 4-[(7-chloro-1,6-naphthyridin-2- yl)methylidene]piperidine-1-carboxylate (2.0 g, 65% purity, 36%) as a light yellow oil.
	With tetrakis-(triphenylphosphine)-palladium; anhydrous sodium carbonate In 1,4-dioxane; water monomer at 100℃; for 40h; Inert atmosphere;	18 tert-butyl 4-[(7-chloro-1,6-naphthyridin-2-yl)methylidene]piperidine-1-carboxylate A mixture of 2,7-dichloro-1,6-naphthyridine (1.98 g, 9.948 mmol, 1 equiv), tert-butyl 4-[(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)methylidene]piperidine-1-carboxylate (6.43 g, 19.896 mmol, 2 equiv), Pd(PPh3)4 (2.30 g, 1.990 mmol, 0.20 equiv) in dioxane (100 mL) and Na2CCh (2.11 g, 19.896 mmol, 2 equiv) in LhO (10 mL, 555.084 mmol, 55.80 equiv) and this resulting mixture was stirred at 100 °C for 40 hours under N2 atmosphere. The reaction mixture was cooled down to room temperature and added H2O (100 mL). The resulting mixture was extracted with EtOAc (3 x 100 mL). The combined organic layers were washed with brine (2x100 mL), dried over anhydrous Na2S04. After filtration, the filtrate was concentrated under reduced pressure to give the residue, which was purified by silica gel column chromatography, eluting with petroleum ether :EtO Ac (4:1 to 2: 1) to afford tert-butyl 4-[(7-chloro-1,6-naphthyridin-2-yl)methylidene]piperidine-1-carboxylate (2.0 g, 65% purity, 36%) as a light yellow oil.
	With tetrakis-(triphenylphosphine)-palladium; anhydrous sodium carbonate In 1,4-dioxane; water monomer at 100℃; for 40h; Inert atmosphere;	18 tert-butyl 4-[(7-chloro-1,6-naphthyridin-2-yl)methylidene]piperidine-1-carboxylate A mixture of 2,7-dichloro-1,6-naphthyridine (1.98 g, 9.948 mmol, 1 equiv), tert-butyl 4-[(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)methylidene]piperidine-1-carboxylate (6.43 g, 19.896 mmol, 2 equiv), Pd(PPh3)4 (2.30 g, 1.990 mmol, 0.20 equiv) in dioxane (100 mL) and Na2CCh (2.11 g, 19.896 mmol, 2 equiv) in LhO (10 mL, 555.084 mmol, 55.80 equiv) and this resulting mixture was stirred at 100 °C for 40 hours under N2 atmosphere. The reaction mixture was cooled down to room temperature and added H2O (100 mL). The resulting mixture was extracted with EtOAc (3 x 100 mL). The combined organic layers were washed with brine (2x100 mL), dried over anhydrous Na2S04. After filtration, the filtrate was concentrated under reduced pressure to give the residue, which was purified by silica gel column chromatography, eluting with petroleum ether :EtO Ac (4:1 to 2: 1) to afford tert-butyl 4-[(7-chloro-1,6-naphthyridin-2-yl)methylidene]piperidine-1-carboxylate (2.0 g, 65% purity, 36%) as a light yellow oil.

Reference： [1]Current Patent Assignee: GOLDFINCH BIO INC - WO2021/67569, 2021, A1 Location in patent: Page/Page column 108-110
[2]Current Patent Assignee: GOLDFINCH BIO INC - WO2022/11274, 2022, A1 Location in patent: Page/Page column 184
[3]Current Patent Assignee: GOLDFINCH BIO INC - WO2022/11274, 2022, A1 Location in patent: Page/Page column 184

42
[ 1425970-61-1 ]
tert-butyl 4-[(7-[[2-fluoro-4-(pyrazol-1-yl)phenyl]amino]-1,6-naphthyridin-2-yl)methylidene]piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: tetrakis-(triphenylphosphine)-palladium; anhydrous sodium carbonate / water monomer / 40 h / 100 °C / Inert atmosphere 2: 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; palladium diacetate; Cs₂CO₃ / 1,4-dioxane / 2 h / 110 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1: tetrakis-(triphenylphosphine)-palladium; anhydrous sodium carbonate / 1,4-dioxane; water monomer / 40 h / 100 °C / Inert atmosphere 2: palladium diacetate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; Cs₂CO₃ / 1,4-dioxane / 2 h / 110 °C / Inert atmosphere