Name: 1370008-65-3|3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)cyclopent-2-enone|98%
Brand: Ambeed
SKU: A696611
Price: 43.0 USD
Availability: InStock
Rating: 95 (32 reviews)

1
[ 51865-32-8 ]
[ 73183-34-3 ]
[ 1370008-65-3 ]

Yield	Reaction Conditions	Operation in experiment
96%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate In 1,4-dioxane at 120℃; for 0.5h; Inert atmosphere;	Step-2 Synthesis of 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclopent-2-en-1-one (Intermediate AA192-3) To a solution of Intermediate AA192-2 (1.5 g, 46.55 mmol) in dioxane (15 mL) was added potassium acetate (2.6 g, 39.65 mmol, 4 eq) followed by dropwise addition of bispinacoline diborane (2.98 g, 40.55 mmol, 3.0 eq). After degassing with argon for 10 mins, PdCl2(dppf)2(0.702 g, 32.74 mmol, 0.07 eq) was added. After stirring at 120° C. for 30 mins, the reaction was quenched with water (500 mL) and extracted by ethyl acetate. The combined organic layer was washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by column chromatography (10% gradient of ethyl acetate in hexane) to afford Intermediate AA192-3 (1.2 g, 96%), MS (ES): m/z 299 [M+1]+
84%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium acetate In 1,4-dioxane at 100℃; for 16h; Inert atmosphere;	7-9 Intermediate 7B: 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclopent-2-en-1-one To a stirred solution of 3-bromocyclopent-2-en-1-one (10 g, 62.1 mmol) in 1,4-dioxane (250 mL) were added bis(pinacolato)diboron (18.93 g, 74.5 mmol) and potassium acetate (12.19 g, 124 mmol). The reaction mixture was degassed with N2 for 10 min, PdCl2(dppf)-CH2Cl2 adduct (3.55 g, 4.35 mmol) was added, and the reaction mixture was stirred at 100° C. for 16 h. The reaction mass was diluted with EtOAc, filtered through Celite, washed with EtOAc, the filtrate was collected and concentrated to get crude product. The crude product was purified by ISCO using silica gel column chromatography, the fractions was collected and concentrated to afford 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclopent-2-en-1-one (10.9 g, 52.4 mmol, 84% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 6.43 (s, 1H), 2.66 (m, 2H), 2.26 (m, 2H), 1.18 (s, 9H).
78%	With potassium acetate In 1,4-dioxane at 20 - 100℃; for 18h; Inert atmosphere;	27.1 1. 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclopent-2-en-1-one Cyclopentane-1,3-dione (5.28 g, 53.8 mmol) and triethylamine (8.25 mL, 59.2 mmol) are added to a stirred suspension of dibromo-triphenyl phosphine (25.08 g, 59.2 mmol) in benzene (100 mL) at room temperature. The resulting mixture is stirred at room temperature for 18 hr, then concentrated in vacuo. The resulting residue is filtered through a pad of silica gel and rinsed with ether. The ether is collected and removed in vacuo and the crude product is purified by chromatograph to give 3-bromocyclopent-2-en-1-one (8.10 g, 94%) as colorless oil. PdCl2(dppf)2 (0.32 g, 0.44 mmol) is added to a degassed mixture of 3-bromocyclopent-2-en-1-one (1.00 g, 6.21 mmol), bis(pinacolato)diboron (1.73 g, 6.83 mmol), KOAc (1.22 g, 12.40 mmol) in 1,4-dioxane (15 mL) at room temperature. The resulting mixture is heated to 100° C. for 18 hr under nitrogen atmosphere. The reaction mixture is concentrated in vacuo and the crude product is purified by chromatograph to give 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclopent-2-en-1-one as a solid (1.00 g, 78%).

61%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate In 1,4-dioxane at 100℃; for 23h; Inert atmosphere; Sealed tube;	135.1 A 100-mL sealed tube was charged with 3-bromocyclopent-2-enone (2.00 g, 12.4 mmol), pinacol diborane (3.47 g, 13.7 mmol), Pd(dppf)Ci2 (0.72 g, 0.88 mmol) and potassium acetate (2.43 g, 24.8 mmol) in dioxane (30 mL). The resulting mixture was heated at 100 °C under argon for 23 h. After this time, the reaction mixture was cooled, filtered through celite washing solids with ethyl acetate, then concentrated under reduced pressure. The residue was purified by chromatography on silica using hexanes/ethyl acetate (10:0 to 1 :2) as eluent to afford the title compound (1.59 g, 61%) as a light yellow solid. MW = 208.06. ]H NMR (CDC13, 500 MHz) δ 6.62 (t, J = 2.0 Hz, 1H), 2.78-2.74 (m, 2H), 2.37- 2.34 (m, 2H), 1.32 (s, 12H).
57%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium acetate In 1,4-dioxane at 100℃; for 16h; Inert atmosphere;	2 Step 2: The stirred solution of 3-bromocyclopent-2-en-1 -one (3.0 g, 18.6 mmol), bis(pinacoato)diboron (4.7 g, 18.6 mmol), KOAc (3.7 g, 37.3 mmol) and PdCI2(dppf)-GH2Cl2 adduct (1 .5 g, 1 .9 mmol) in 1 ,4-dioxane (60 mL) was degassed with nitrogen for 10 min and heated at 100 >C under nitrogen for 16 h. The reaction mixture was diluted with water and extracted with EtOAc thrice. The combined organic solution was washed with brine, dried over anhydrous Na2S0 and concentrated in vacuo. The crude residue was purified on silica gel (EtOAc/hexane, 30-40%) to afford 3-(4,4,5,5-tetramethyl-1 ,3,2-dioxaboroian-2- yl)cyclopent-2-en-1 -one (2 2 g, 57% yield) as a pale yellow liquid: 1H NMR (300 MHz, CDCb) d 6 23 (t, J= 2 4 Hz, 1 H), 2.78 - 2.74 (m, 2H), 2.37 - 2.34 (m, 2H), 1 .32 (s, 12H).
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium acetate In 1,4-dioxane at 90℃; Inert atmosphere;	11.2 Step 2. 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclopent-2-enone Step 2. 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclopent-2-enone To a solution of 3-bromocyclopent-2-enone (13 g, 81 mmol) in dioxane (161 mL) was added B2(PIN)2 (41.0 g, 161 mmol) and PdCl2(dppf)CH2Cl2 (2.95 g, 4.04 mmol). The reaction mixture was degassed for 15 min by N2 bubbling. Then KOAc (23.77 g, 242 mmol) was added. The reaction mixture was heated at 90° C. overnight. After cooling down, the reaction mixture was filtered off through a frit glass filter and rinsed with dioxane (160 mL), the filtrate was concentrated in vacuo yielding crude 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclopent-2-enone, which was used for the next step without purification. LCMS (m/z): 126.9 (MH+), 0.17 min.
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate In 1,4-dioxane at 100℃; for 16h; Sealed tube; Inert atmosphere;	11 Synthesis of 3-(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) cyclopent-2-en-1-one (63): To a stirring solution of compound 62 (2.5 g, crude) in 1,4-dioxane (100 mL) were added Bis(pinacolato) diboron (4 g, 15.62 mmol) and potassium acetate (3.06 g, 31.25 mmol) in a sealed tube at RT and purged under argon for 30 mm. Then Pd(dppf)C12 (1.14 g, 1.56 mmol) was added at RT. The reaction mixture was heated to 100 °C and stirred for 16 h. The reaction was monitored by TLC; after completion of the reaction, the reaction mixture was filtered through a pad of celite and the celite bed was washed with 5% MeOH/ CH2C12 (50 mL). The filtrate was concentrated in vacuo to afford compound 63 (3.2 g) as black syrup. This crude material was taken to next step without further purification. TLC: 20% EtOAc/ hexanes (Rf:0.3).

Reference： [1]Current Patent Assignee: NIMBUS THERAPEUTICS INC; CHARLES RIVER LABORATORIES INTERNATIONAL INC; NIMBUS SATURN - US2021/78996, 2021, A1 Location in patent: Paragraph 0979; 0981
[2]Current Patent Assignee: BIOCON LIMITED; BRISTOL-MYERS SQUIBB CO - US2019/185469, 2019, A1 Location in patent: Paragraph 0564-0565
[3]Current Patent Assignee: Wang, Zhong; Smith, Emilie D.; Veal, James M.; Huang, Kenneth H.; Atkinson, Robert N.; Jiang, Rong - US2012/77814, 2012, A1 Location in patent: Page/Page column 55
[4]Current Patent Assignee: TETRA DISCOVERY PARTNERS - WO2014/66659, 2014, A1 Location in patent: Paragraph 0732
[5]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - WO2020/128768, 2020, A1 Location in patent: Page/Page column 218-219
[6]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - US9242996, 2016, B2 Location in patent: Page/Page column 93; 94; 95
[7]Current Patent Assignee: ASSEMBLY BIOSCIENCES, INC. - WO2018/53157, 2018, A1 Location in patent: Page/Page column 77; 78

2
[ 3859-41-4 ]
[ 1370008-65-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: bromine; triethylamine; triphenylphosphine / benzene / 20 °C 2: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium acetate / 1,4-dioxane / 90 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1: phosphorus tribromide / chloroform / 5 h / 0 - 80 °C / Inert atmosphere 2: potassium acetate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane / 16 h / 100 °C / Sealed tube; Inert atmosphere
	Multi-step reaction with 2 steps 1: triethylamine; dibromotriphenylphosphorane / benzene / 18 h / 20 °C 2: potassium acetate / PdCl₂(dppf)2 / 1,4-dioxane / 18 h / 20 - 100 °C / Inert atmosphere

	Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 1 h / 0 °C 2: potassium acetate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1 h / 100 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1: triethylamine; bromine; triphenylphosphine / dichloromethane / 16 h / 20 °C 2: potassium acetate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / 1,4-dioxane / 16 h / 100 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1: triethylamine; dibromotriphenylphosphorane / benzene / 6 h / 20 °C / Inert atmosphere 2: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium acetate / 1,4-dioxane / 16 h / 100 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1: triphenylphosphine; bromine; triethylamine / dichloromethane / 0.33 h / 20 °C 2: potassium acetate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane / 0.5 h / 120 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine / dichloromethane / 20 °C / Cooling with ice 2: palladium diacetate; tris(o-methoxyphenyl)phosphine / acetone; water / 18 h / 20 °C

Reference： [1]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - US9242996, 2016, B2
[2]Current Patent Assignee: ASSEMBLY BIOSCIENCES, INC. - WO2018/53157, 2018, A1
[3]Current Patent Assignee: Wang, Zhong; Smith, Emilie D.; Veal, James M.; Huang, Kenneth H.; Atkinson, Robert N.; Jiang, Rong - US2012/77814, 2012, A1
[4]Current Patent Assignee: ROCHE HOLDING AG - US2018/282328, 2018, A1
[5]Current Patent Assignee: BIOCON LIMITED; BRISTOL-MYERS SQUIBB CO - US2019/185469, 2019, A1
[6]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - WO2020/128768, 2020, A1
[7]Current Patent Assignee: NIMBUS THERAPEUTICS INC; CHARLES RIVER LABORATORIES INTERNATIONAL INC; NIMBUS SATURN - US2021/78996, 2021, A1
[8]Gaube, Gregory; Leitch, David C.; Pipaon Fernandez, Nahiane [New Journal of Chemistry, 2021, vol. 45, # 43, p. 20095 - 20098]

3
[ 1370008-65-3 ]
[ 1370007-44-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 11 steps 1.1: potassium phosphate / bis-triphenylphosphine-palladium(II) chloride / 1,4-dioxane; water / 12 h / 80 °C 2.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -78 °C 2.2: 2 h / -78 °C 3.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 16 h / 0 - 20 °C 4.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 16 h / 0 - 20 °C 5.1: dimethylsulfide borane complex / tetrahydrofuran / 1 h / 0 °C 6.1: hydrogen / {Rh[(R,R)-Me-Duphos](COD)}BF₄ / dichloromethane / 16 h 7.1: triethylamine / dichloromethane / 2 h / 0 - 20 °C 8.1: 1,2-dimethoxyethane / 3 h / 150 °C / Microwave irradiation 9.1: bromocatecholborane / dichloromethane / 1 h / -78 °C 10.1: sulphamoyl chloride; triethylamine / acetonitrile / 6 h / 20 °C 11.1: trifluoroacetic acid / dichloromethane / 3 h / 20 °C

Reference： [1]Current Patent Assignee: Wang, Zhong; Smith, Emilie D.; Veal, James M.; Huang, Kenneth H.; Atkinson, Robert N.; Jiang, Rong - US2012/77814, 2012, A1

4
[ 1370008-65-3 ]
[ 1370008-68-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: potassium phosphate / bis-triphenylphosphine-palladium(II) chloride / 1,4-dioxane; water / 12 h / 80 °C 2.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -78 °C 2.2: 2 h / -78 °C

Reference： [1]Current Patent Assignee: Wang, Zhong; Smith, Emilie D.; Veal, James M.; Huang, Kenneth H.; Atkinson, Robert N.; Jiang, Rong - US2012/77814, 2012, A1

5
[ 1370008-65-3 ]
[ 1370008-69-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: potassium phosphate / bis-triphenylphosphine-palladium(II) chloride / 1,4-dioxane; water / 12 h / 80 °C 2.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -78 °C 2.2: 2 h / -78 °C 3.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 16 h / 0 - 20 °C 4.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 16 h / 0 - 20 °C

Reference： [1]Current Patent Assignee: Wang, Zhong; Smith, Emilie D.; Veal, James M.; Huang, Kenneth H.; Atkinson, Robert N.; Jiang, Rong - US2012/77814, 2012, A1

6
[ 1370008-65-3 ]
[ 1370008-70-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: potassium phosphate / bis-triphenylphosphine-palladium(II) chloride / 1,4-dioxane; water / 12 h / 80 °C 2.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -78 °C 2.2: 2 h / -78 °C 3.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 16 h / 0 - 20 °C

Reference： [1]Current Patent Assignee: Wang, Zhong; Smith, Emilie D.; Veal, James M.; Huang, Kenneth H.; Atkinson, Robert N.; Jiang, Rong - US2012/77814, 2012, A1

7
[ 1370008-65-3 ]
[ 1370008-73-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: potassium phosphate / bis-triphenylphosphine-palladium(II) chloride / 1,4-dioxane; water / 12 h / 80 °C 2.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -78 °C 2.2: 2 h / -78 °C 3.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 16 h / 0 - 20 °C 4.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 16 h / 0 - 20 °C 5.1: dimethylsulfide borane complex / tetrahydrofuran / 1 h / 0 °C 6.1: hydrogen / {Rh[(R,R)-Me-Duphos](COD)}BF₄ / dichloromethane / 16 h

Reference： [1]Current Patent Assignee: Wang, Zhong; Smith, Emilie D.; Veal, James M.; Huang, Kenneth H.; Atkinson, Robert N.; Jiang, Rong - US2012/77814, 2012, A1

8
[ 1370008-65-3 ]
[ 1370008-76-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 9 steps 1.1: potassium phosphate / bis-triphenylphosphine-palladium(II) chloride / 1,4-dioxane; water / 12 h / 80 °C 2.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -78 °C 2.2: 2 h / -78 °C 3.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 16 h / 0 - 20 °C 4.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 16 h / 0 - 20 °C 5.1: dimethylsulfide borane complex / tetrahydrofuran / 1 h / 0 °C 6.1: hydrogen / {Rh[(R,R)-Me-Duphos](COD)}BF₄ / dichloromethane / 16 h 7.1: triethylamine / dichloromethane / 2 h / 0 - 20 °C 8.1: 1,2-dimethoxyethane / 3 h / 150 °C / Microwave irradiation 9.1: bromocatecholborane / dichloromethane / 1 h / -78 °C

Reference： [1]Current Patent Assignee: Wang, Zhong; Smith, Emilie D.; Veal, James M.; Huang, Kenneth H.; Atkinson, Robert N.; Jiang, Rong - US2012/77814, 2012, A1

9
[ 1370008-65-3 ]
[ 1370008-77-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 8 steps 1.1: potassium phosphate / bis-triphenylphosphine-palladium(II) chloride / 1,4-dioxane; water / 12 h / 80 °C 2.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -78 °C 2.2: 2 h / -78 °C 3.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 16 h / 0 - 20 °C 4.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 16 h / 0 - 20 °C 5.1: dimethylsulfide borane complex / tetrahydrofuran / 1 h / 0 °C 6.1: hydrogen / {Rh[(R,R)-Me-Duphos](COD)}BF₄ / dichloromethane / 16 h 7.1: triethylamine / dichloromethane / 2 h / 0 - 20 °C 8.1: 1,2-dimethoxyethane / 3 h / 150 °C / Microwave irradiation

Reference： [1]Current Patent Assignee: Wang, Zhong; Smith, Emilie D.; Veal, James M.; Huang, Kenneth H.; Atkinson, Robert N.; Jiang, Rong - US2012/77814, 2012, A1

10
[ 1370008-65-3 ]
[(1S,2S,4R)-2-[tert-butyl(dimethyl)silyl]oxy-4-[4-(cyclohexylmethylamino)thieno[3,2-d]pyrimidin-7-yl]cyclopentyl]methyl sulfamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 10 steps 1.1: potassium phosphate / bis-triphenylphosphine-palladium(II) chloride / 1,4-dioxane; water / 12 h / 80 °C 2.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -78 °C 2.2: 2 h / -78 °C 3.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 16 h / 0 - 20 °C 4.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 16 h / 0 - 20 °C 5.1: dimethylsulfide borane complex / tetrahydrofuran / 1 h / 0 °C 6.1: hydrogen / {Rh[(R,R)-Me-Duphos](COD)}BF₄ / dichloromethane / 16 h 7.1: triethylamine / dichloromethane / 2 h / 0 - 20 °C 8.1: 1,2-dimethoxyethane / 3 h / 150 °C / Microwave irradiation 9.1: bromocatecholborane / dichloromethane / 1 h / -78 °C 10.1: sulphamoyl chloride; triethylamine / acetonitrile / 6 h / 20 °C

Reference： [1]Current Patent Assignee: Wang, Zhong; Smith, Emilie D.; Veal, James M.; Huang, Kenneth H.; Atkinson, Robert N.; Jiang, Rong - US2012/77814, 2012, A1

11
[ 1370008-67-5 ]
[ 1370008-65-3 ]
[ 1370008-66-4 ]

Yield	Reaction Conditions	Operation in experiment
73%	With potassium phosphate In 1,4-dioxane; water at 80℃; for 12h;	27.2 PdCl2(PPh3)2 (1.65 g, 2.35 mmol) is added to a solution of 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclopent-2-en-1-one (8.10 g, 38.9 mmol), 7-bromo-4-tert-butylsulfanyl-thieno[3,2-d]pyrimidine (10.30 g, 33.9 mmol) and K3PO4 (21.52 g, 101 mmol) in a mixture of 1,4-dioxane (250 mL) and water (50 mL). The resulting mixture is heated to 80° C. for 12 hr and concentrated in vacuo. The crude residue is purified by chromatograph to give desired title product as a solid (7.65 g, 73%). LCMS (m/z) M+H=305.4; tR=3.27 min.

Reference： [1]Current Patent Assignee: Wang, Zhong; Smith, Emilie D.; Veal, James M.; Huang, Kenneth H.; Atkinson, Robert N.; Jiang, Rong - US2012/77814, 2012, A1 Location in patent: Page/Page column 56

12
[ 56946-65-7 ]
[ 1370008-65-3 ]
[ 1606976-92-4 ]

Yield	Reaction Conditions	Operation in experiment
23%	With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In ethanol; water; toluene; at 90.0℃; for 18h;Inert atmosphere;	A 250-mL round bottomed flask was charged with 2,4-dichloro-6,7-dihydro-5H- cyclopenta[Z?]pyridine (1.05 g, 5.58 mmol), 3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2- yl)cyclopent-2-enone (1.27 g, 6.14 mmol), tetrakis(triphenylphosphine)palladium(0) (0.322 g, 0.28 mmol), and Cs2C03 (5.45 g, 16.7 mmol). Toluene (30 ml), EtOH (7.5 ml) and water (15 ml) were added. The resulting mixture was stirred under argon at 90 C for 18 h. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate (150 mL), hexanes (50 mL) and water (25 mL). The aqueous layer was separated and extracted with ethyl acetate (2 x 100 mL). The combined organic extract was washed with saturated sodium chloride (2 x 20 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on silica using hexane/ethyl acetate (10:0 to 0: 10) as eluent to afford the title compound (0.305 g, 23%) as a yellow solid. MW = 233.69. ]H NMR (CDC13, 500 MHz) delta 7.41 (s, 1H), 6.79 (t, 7 = 2.0 Hz, 1H), 3.13 (t, 7 = 7.5 Hz, 2H), 3.10-3.06 (m, 2H), 3.04 (t, 7 = 7.5 Hz, 2H), 2.62-2.58 (m, 2H), 2.20 (quin, 7 = 7.5 Hz, 2H).

Reference： [1]Patent: WO2014/66659,2014,A1 .Location in patent: Paragraph 0733

13
[ 1370008-65-3 ]
[ 1606976-93-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: caesium carbonate; tetrakis(triphenylphosphine) palladium⁽⁰⁾ / toluene; ethanol; water / 18 h / 90 °C / Inert atmosphere 2: dimethylsulfide borane complex / tetrahydrofuran / 4 h / 55 °C

Reference： [1]Current Patent Assignee: TETRA DISCOVERY PARTNERS - WO2014/66659, 2014, A1

14
[ 1370008-65-3 ]
[ 1606976-94-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: caesium carbonate; tetrakis(triphenylphosphine) palladium⁽⁰⁾ / toluene; ethanol; water / 18 h / 90 °C / Inert atmosphere 2: dimethylsulfide borane complex / tetrahydrofuran / 4 h / 55 °C 3: caesium carbonate; palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl / 1,4-dioxane / 2 h / 120 °C / Inert atmosphere; Microwave irradiation

Reference： [1]Current Patent Assignee: TETRA DISCOVERY PARTNERS - WO2014/66659, 2014, A1

15
[ 1370008-65-3 ]
tert-butyl (6-chloro-[1,2,4]triazolo[1,5-a]pyridine-8-yl)(6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-yl)carbamate [ No CAS ]
tert-butyl (6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-yl)(6-(3-oxocyclopent-1-en-1-yl)-[1,2,4]triazolo[1,5-a]pyridine-8-yl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
53.7%	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾ In water; toluene at 100℃; Inert atmosphere; Microwave irradiation;	8.C St C:II,24IdrhaikI1,5-aIpMin-8-yIJ’cathama±e A xnuaid bottom flask was charged with ten-bufi 6

Reference： [1]Current Patent Assignee: ABBVIE INC - WO2015/157955, 2015, A1 Location in patent: Page/Page column 97

16
[ 1370008-65-3 ]
N-(6-bromopyridazin-3-yl)-2-(pyridin-2-yl)acetamide [ No CAS ]
N-[6-(3-oxocyclopent-1-en-1-yl)pyridazin-3-yl]-2-(pyridin-2-yl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; cesium fluoride In tetrahydrofuran; water at 20 - 100℃; for 18h; Inert atmosphere;	26.1 Preparation of /V-[6-(3-oxocvclopent-1 -en-1 -yl)pyridazin-3-yl1-2-(pyridin-2- vQacetamide To a 100 ml_ pressure flask charged with /V-(6-bromopyridazin-3-yl)-2-(pyridin-2- yl)-acetamide (5 g, 17.1 mmol), 3-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2- yl)cyclopent-2-en-1 -one (10.7 g, 51 .2 mmol), Pd(dppf)CI2 (1 .39 g, 1 .71 mmol), and CsF 13.0 g, 85.4 mmol) was added THF (142 mL) and water (22.9 mL) under nitrogen. After 5 min at room temperature with stirring and nitrogen bubbling, the reaction vessel was placed in a pre-heated 100 °C sand bath behind a blast shield. After 18 hr, the mixture was cooled to room temperature, concentrated, diluted with 750 mL CH2CI2 and allowed to stir for 15 min. The suspension was filtered through a plug of Celite and concentrated. The residue was purified by silica gel chromatography eluting with 0 - 5% EtOH in EtOAc to provide /V-[6-(3-oxocyclopent-1 -en-1 -yl)pyridazin-3-yl]-2-(pyridin-2- yl)acetamide (3.75 g, 75%) as a solid. 1 H NMR (400 MHz, CDCI3) δ ppm 8.69 - 8.72 (m, 1 H), 8.56 (d, J = 8 Hz, 2 H), 7.78 - 7.82 (m, 2 H), 7.35 - 7.39 (m, 2 H), 6.76 (s, 1 H), 4.08 (s, 2 H), 3.27 - 3.29 (m, 2 H), 2.62 - 2.65 (m, 2 H). m/z (APCI+) for Ci6H14N402 295.1 (M+H)+.

Reference： [1]Current Patent Assignee: PFIZER INC - WO2015/166373, 2015, A1 Location in patent: Page/Page column 143; 144

17
[ 1370008-65-3 ]
N-[6-(3-oxocyclopentyl)pyridazin-3-yl]-2-(pyridin-2-yl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; cesium fluoride / tetrahydrofuran; water / 18 h / 20 - 100 °C / Inert atmosphere 2: palladium 10% on activated carbon; hydrogen / methanol / 25 h / 50 °C / 3000.3 - 4500.45 Torr / Autoclave

Reference： [1]Current Patent Assignee: PFIZER INC - WO2015/166373, 2015, A1

18
[ 1370008-65-3 ]
N-{6-[(3E)-3-(cyanomethylidene)cyclopentyl]pyridazin-3-yl}-2-(pyridin-2-yl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; cesium fluoride / tetrahydrofuran; water / 18 h / 20 - 100 °C / Inert atmosphere 2.1: palladium 10% on activated carbon; hydrogen / methanol / 25 h / 50 °C / 3000.3 - 4500.45 Torr / Autoclave 3.1: sodium hydride / tetrahydrofuran / 0.17 h / 0 - 20 °C 3.2: 3 h

Reference： [1]Current Patent Assignee: PFIZER INC - WO2015/166373, 2015, A1

19
[ 1370008-65-3 ]
N-{6-[3-(cyanomethyl)cyclopentyl]pyridazin-3-yl}-2-(pyridin-2-yl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; cesium fluoride / tetrahydrofuran; water / 18 h / 20 - 100 °C / Inert atmosphere 2.1: palladium 10% on activated carbon; hydrogen / methanol / 25 h / 50 °C / 3000.3 - 4500.45 Torr / Autoclave 3.1: sodium hydride / tetrahydrofuran / 0.17 h / 0 - 20 °C 3.2: 3 h 4.1: L-Selectride / tetrahydrofuran / 4 h / -78 °C

Reference： [1]Current Patent Assignee: PFIZER INC - WO2015/166373, 2015, A1

20
[ 1370008-65-3 ]
2-(pyridin-2-yl)-N-{5-[(3-{6-[(pyridin-2-ylacetyl)amino]pyridazin-3-yl}cyclopentyl)methyl]-1,3,4-thiadiazol-2-yl}acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; cesium fluoride / tetrahydrofuran; water / 18 h / 20 - 100 °C / Inert atmosphere 2.1: palladium 10% on activated carbon; hydrogen / methanol / 25 h / 50 °C / 3000.3 - 4500.45 Torr / Autoclave 3.1: sodium hydride / tetrahydrofuran / 0.17 h / 0 - 20 °C 3.2: 3 h 4.1: L-Selectride / tetrahydrofuran / 4 h / -78 °C 5.1: trifluoroacetic acid / 4 h / 70 °C 6.1: pyridine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / N,N-dimethyl-formamide / 2 h / 20 °C

Reference： [1]Current Patent Assignee: PFIZER INC - WO2015/166373, 2015, A1

21
[ 1370008-65-3 ]
C₁₉H₂₁N₇OS [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; cesium fluoride / tetrahydrofuran; water / 18 h / 20 - 100 °C / Inert atmosphere 2.1: palladium 10% on activated carbon; hydrogen / methanol / 25 h / 50 °C / 3000.3 - 4500.45 Torr / Autoclave 3.1: sodium hydride / tetrahydrofuran / 0.17 h / 0 - 20 °C 3.2: 3 h 4.1: L-Selectride / tetrahydrofuran / 4 h / -78 °C 5.1: trifluoroacetic acid / 4 h / 70 °C

Reference： [1]Current Patent Assignee: PFIZER INC - WO2015/166373, 2015, A1

22
[ 1370008-65-3 ]
2,6-dichloro-N-((1-hydroxy-3-methylcyclohexyl)methyl)quinoline-5-carboxamide [ No CAS ]
6-chloro-2-(3-oxo-cyclopent-1-enyl)quinoline-5-carboxylic acid (1-hydroxy-3-methylcyclohexylmethyl)amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; cesium fluoride In 1,4-dioxane; water at 130℃; for 1.25h; Microwave irradiation; Inert atmosphere;	137.1 Step 1. 6-Chloro-2-(3-oxo-cyclopent-1-enyl)-quinoline-5-carboxylic acid (1-hydroxy-3- methylcyclo hexyl methyl)- amide Step 1. 6-Chloro-2-(3-oxo-cyclopent-1-enyl)-quinoline-5-carboxylic acid (1-hydroxy-3- methylcyclo hexyl methyl)- amide[00361] The title compound was synthesized accordingto the procedure described in example 125using 2,6-dichloro-quinoline-5-carboxylic acid (1-hydroxy-3-methyl-cyclohexylmethyl) amide,cesium carbonate, 3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)- cyclopent-2-enoneand [1,1-bis (diphenylphosphino)ferrocene] dichloropalladium(II). 1H NMR (400 MHz, DMSO d6) 8ppm: 8.70 (t, J = 6.04 Hz, 1H), 8.28-8.22 (m, 2H), 8.12 (d, J = 9.21 Hz, 1H), 7.86 (d, J =9.03 Hz, 1H), 7.13 (t, J = 1.64 Hz, 1H), 4.21 (s, 1H), 3.22-3.20(m, 2H), 2.56-2.54 (m, 2H), 1.73 (t, J = 3.41 Hz, 1H), 1.62-1.56 (m, 4H), 1.48-1.45(m, 1H), 1.32-1.25 (m, 1H), 1.06-1.00 (m,1H), 0.84 (d, J = 6.63 Hz, 3H), 0.77-0.74 (m, 1H). m/z: 413.2 [M + H] +

Reference： [1]Current Patent Assignee: MERCK KGAA - WO2015/187905, 2015, A1 Location in patent: Paragraph 00345; 00361

23
[ 59489-71-3 ]
[ 1370008-65-3 ]
3-(5-aminopyrazin-2-yl)cyclopent-2-enone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; sodium carbonate In water at 100℃;	11.3 Step 3. 3-(5-aminopyrazin-2-yl)cyclopent-2-enone Step 3. 3-(5-aminopyrazin-2-yl)cyclopent-2-enone To 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclopent-2-enone (2.99 g, 14.37 mmol) (the filtrate from last step) was added 2-amino-5 bromopyrazine (2.5 g, 14.37 mmol), PdCl2(dppf)-CH2Cl2 (1.173 g, 1.437 mmol), Na2CO3 (7.61 g, 71.8 mmol) and water (17.96 mL) the reaction mixture was stirred at 100° C. oil bath for overnight, filtered through Celite. The reaction mixture was then extracted by EtOAc. The organic was then used 3N HCl (20 mL) washed 2 times, and water 50 mL once, the AQ was then neutralized by NaOH to pH=8, the reaction mixture was then extracted by CHCl3/IPA (7:3) 3 times, the organic was dried and concentrated and used as it. LCMS (m/z): 176.1 (MH+), 0.32 min.

Reference： [1]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - US9242996, 2016, B2 Location in patent: Page/Page column 93; 94; 95

24
[ 1370008-65-3 ]
N,N-di-tert-butyl (5-(3-oxocyclopent-1-en-1-yl)pyrazin-2-yl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: sodium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / water / 100 °C 2: dmap / dichloromethane / 5 h / 20 °C

Reference： [1]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - US9242996, 2016, B2

25
[ 1370008-65-3 ]
(+/-)-N,N-di-tert-butyl (5-(3-oxocyclopentyl)pyrazin-2-yl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: sodium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / water / 100 °C 2: dmap / dichloromethane / 5 h / 20 °C 3: hydrogen; palladium on activated charcoal / methanol / 2 h / 20 °C

Reference： [1]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - US9242996, 2016, B2

26
[ 1370008-65-3 ]
(+/-)-N,N-di-tert-butyl (5-((1R,3R)-3-hydroxycyclopentyl)pyrazin-2-yl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: sodium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / water / 100 °C 2: dmap / dichloromethane / 5 h / 20 °C 3: hydrogen; palladium on activated charcoal / methanol / 2 h / 20 °C 4: methanol; sodium tetrahydroborate / 0.5 h / 20 °C

Reference： [1]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - US9242996, 2016, B2

27
[ 1370008-65-3 ]
(+/-)-N,N-di-tert-butyl (5-((1R,3S)-3-hydroxycyclopentyl)pyrazin-2-yl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: sodium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / water / 100 °C 2: dmap / dichloromethane / 5 h / 20 °C 3: hydrogen; palladium on activated charcoal / methanol / 2 h / 20 °C 4: methanol; sodium tetrahydroborate / 0.5 h / 20 °C

Reference： [1]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - US9242996, 2016, B2

28
[ 1370008-65-3 ]
(+/-)-(1S,3R)-3-(5-amino-6-bromopyrazin-2-yl)cyclopentanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: sodium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / water / 100 °C 2: dmap / dichloromethane / 5 h / 20 °C 3: hydrogen; palladium on activated charcoal / methanol / 2 h / 20 °C 4: methanol; sodium tetrahydroborate / 0.5 h / 20 °C 5: hydrogenchloride / dichloromethane; water / 20 °C 6: N-Bromosuccinimide / acetonitrile / 0.5 h / 20 °C

Reference： [1]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - US9242996, 2016, B2

29
[ 1370008-65-3 ]
(+/-)-(1S,3R)-3-(5-aminopyrazin-2-yl)cyclopentanol hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: sodium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / water / 100 °C 2: dmap / dichloromethane / 5 h / 20 °C 3: hydrogen; palladium on activated charcoal / methanol / 2 h / 20 °C 4: methanol; sodium tetrahydroborate / 0.5 h / 20 °C 5: hydrogenchloride / dichloromethane; water / 20 °C

Reference： [1]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - US9242996, 2016, B2

30
[ 1370008-65-3 ]
7-chloro-5-methoxy-8-methyl-1,6-naphthyridine [ No CAS ]
3-(5-methoxy-8-methyl-1,6-naphthyridin-7-yl)cyclopent-2-en-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	With potassium phosphate; palladium diacetate; ruphos In 1,4-dioxane at 20 - 110℃; for 1h; Inert atmosphere; Microwave irradiation;	10.5 Step 5: 3-(5-methoxy-8-methyl- 1 ,6-naphthyridin-7-yl)cyclopent-2-en- 1-one (Compound 9e) To a solution of 7-chloro-5-methoxy-8-methyl- l ,6-naphthyridine (Compound 9d, 1.5g, 7.188 mmol) and 3-(4,4,5,5-tetramethyl- l ,3,2-dioxaborolan-2- yl)cyclopent-2-enone (1.644 g, 7.92 mmol) (Synthesis reported in US2012/77814) in 1 ,4 Dioxane (15 ml) was added tripotassium phosphate (4.578 g, 21.57 mmol) and dicyclohexyl-[2-[2,6-di(propan-2-yloxy)phenyl]phenyl]phosphane (267 mg, 0.576 mmol) at room temperature under nitrogen purging in a microwave reaction tube for 15 minutes and Pd(OAc)2 (65 mg, 0.30 mmol) was added to the reaction mixture. The reaction mixture was heated for 1 hr at 1 10°C in microwave. The progress of reaction was monitored by TLC. The reaction mixture was diluted with water (50 ml) and ethyl acetate (50 ml). The phases were separated and the aqueous phase was extracted with ethyl acetate (2 x 20 ml). The combined organic layer was dried over anhydrous sodium sulphate. The solvent in the organic layer was evaporated under reduced pressure to obtain a crude product. The crude product was purified by flash column chromatography over silica gel (100-200 mesh) using 40% ethyl acetate in hexane as an eluent to obtain the title compound ( 1.5 g, 82% yield). iH NMR (400 MHz, CDC13) δ 9.13 (d, 1H), 8.58 (d, J = 8.3 Hz, 1H), 7.54 (dd, J = 8.2, 4.3 Hz, 1H), 6.61 (s, 1H), 4.16 (s, 3H), 3.36 - 3.28 (m, 2H), 2.82 (s, 3H), 2.66 - 2.59 (m, 2H). MS: m/z 255 (M+ l).

Reference： [1]Current Patent Assignee: LUPIN LIMITED - WO2017/29601, 2017, A1 Location in patent: Page/Page column 145-146

31
[ 1370008-65-3 ]
[ 344331-90-4 ]
tert-butyl N-[6-(3-oxocyclopent-1-en-1-yl)pyridin-2-yl]carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In N,N-dimethyl-formamide; at 100℃;Inert atmosphere;	A mixture of 3 -(4,4,5,5 ,-tetramethyl- 1,3 ,2-dioxaborolan-2-yl)cyclopent-2-enone (500 mg, 2.4 mmol), <strong>[344331-90-4]tert-butyl 6-bromopyridin-2-ylcarbamate</strong> (656 mg, 2.4 mmol), Pd(dppf)Cl2 (176 mg, 0.24 mmol), Na2CO3 (509 mg, 4.8 mmol), DMF (16 mL) and water (4 mL) was stirred at 100 C under N2 overnight. The mixture was extracted with EA (60 mL2), washed with brine (20 mL3), dried over Na2SO4 and concentrated to dryness. The residue was purified by column chromatography (EADCM=020%). ESI: m/z 275.2 (M+H)+

Reference： [1]Patent: WO2017/106352,2017,A1 .Location in patent: Paragraph 000789

32
[ 1370008-65-3 ]
tert-butyl 6-(3-oxocyclopentyl)pyridine-2-ylcarbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate / N,N-dimethyl-formamide / 100 °C / Inert atmosphere 2: palladium on activated charcoal; hydrogen / methanol / 20 °C

Reference： [1]Current Patent Assignee: RAZE THERAPEUTICS; EVOTEC AG - WO2017/106352, 2017, A1

33
[ 1370008-65-3 ]
3-(6-aminopyridin-2-yl)cyclopentanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate / N,N-dimethyl-formamide / 100 °C / Inert atmosphere 2: palladium on activated charcoal; hydrogen / methanol / 20 °C 3: hydrogenchloride / methanol / 4 h / 20 °C

Reference： [1]Current Patent Assignee: RAZE THERAPEUTICS; EVOTEC AG - WO2017/106352, 2017, A1

34
[ 1370008-65-3 ]
3-(6-aminopyridin-2-yl)cyclopentanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate / N,N-dimethyl-formamide / 100 °C / Inert atmosphere 2: palladium on activated charcoal; hydrogen / methanol / 20 °C 3: hydrogenchloride / methanol / 4 h / 20 °C 4: sodium tetrahydroborate / methanol / 2 h / 20 °C

Reference： [1]Current Patent Assignee: RAZE THERAPEUTICS; EVOTEC AG - WO2017/106352, 2017, A1

35
[ 1370008-65-3 ]
N-((2-chlorothiazol-5-yl)methyl)-11-oxo-10,11-dihydrodibenzo[b,f][1,4]thiazepine-8-carboxamide 5,5-dioxide [ No CAS ]
11-oxo-N-((2-(3-oxocyclopent-1-en-1-yl)thiazol-5-yl)methyl)-10,11-dihydrodibenzo[b,f][1,4]thiazepine-8-carboxamide 5,5-dioxide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
27%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate In 1,2-dimethoxyethane; water at 120℃; for 16h; Sealed tube; Inert atmosphere;	12 Synthesis of 11-oxo-N-((2-(3-oxocyclopent-1-en-1-yl) thiazol-5-yl) methyl)-10, 11- dihydrodibenzo [b, f] [1, 4] thiazepine-8-carboxamide 5, 5-dioxide (69): To a stirring solution of N-((2-chlorothiazol-5-yl) methyl)- 11 -oxo- 10,11 -dihydrodibenzo [b, fI [1, 41 thiazepine-8-carboxamide 5, 5-dioxide 67 (500 mg, 1.15 mmol) in amixture of dimethoxyethane/water (4:1, 20 mL) were added 3-(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) cyclopent-2-en-1-one 68 (720 mg, 3.46 mmol) and sodium carbonate (428mg, 4.03 mmol) in a sealed tube at RT and purged under argon for 30 mm. Then Pd(dppf)C12 (84mg, 0.11 mmol) was added at RT. The reaction mixture was heated to 120 °C and stirred for 16The reaction was monitored by TLC; after completion of the reaction, the volatiles wereremoved in vacuo to obtain the crude. The crude was purified through column chromatography using 3% MeOH/ CH2C12 followed by washings with EtOAc (2 x 10 mL) to afford compound 69 (150 mg, 27%) as white solid. TLC: 5% MeOH/ CH2C12 (Rf: 0.4); ‘H NMR (400MHz, DMSOd 6): ö 11.53 (s, 1H), 9.53 (t, J= 5.6 Hz, 1H), 8.06 (d, J= 8.3 Hz, 1H), 8.01-7.95 (m, 3H), 7.90(td, J = 7.4, 1.4 Hz, 1H), 7.88-7.79 (m, 3H), 6.67 (t, J = 1.8 Hz, 1H), 4.73 (d, J = 5.6 Hz, 2H),3.05-3.02 (m, 2H), 2.48-2.46 (m, 2H); LC-MS: 91.36%; 480.1 (M+1) (column; Kinetex EVO C-18 (50 x 3.0 mm, 2.6 urn); RT 2.18 mm. 2.5 mM NH400CH in water + 5% ACN: ACN + 5% 2.5 rnM NH400CH in water, 0.8 mL/min).

Reference： [1]Current Patent Assignee: ASSEMBLY BIOSCIENCES, INC. - WO2018/53157, 2018, A1 Location in patent: Page/Page column 80; 81; 82

36
[ 1370008-65-3 ]
tert-butyl ((2-chlorothiazol-5-yl)methyl)carbamate [ No CAS ]
tert-butyl ((2-(3-oxocyclopent-1-en-1-yl)thiazol-5-yl)methyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
600 mg	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate In 1,2-dimethoxyethane; water at 120℃; for 16h; Sealed tube; Inert atmosphere;	11 Synthesis of tert-butyl ((2-(3-oxocyclopent-1-en-1-yl) thiazol-5-yl) methyl) carbamate (58): To a stirring solution of tert-butyl ((2-chlorothiazol-5 -yl) methyl) carbamate 57 (1 g, 4.02 mmol) in a mixture of dimethoxyethane/water (4:1, 40 mL) were added compound 63 (2.5 g, crude) and sodium carbonate (1.49 g, 14.11 mmol) in a sealed tube at RT and purged underargon for 30 mm. Then Pd(dppf)C12 (295 mg, 0.4 mmol) was added at RT. The reaction mixture was heated to 120 °C and stirred for 16 h. The reaction was monitored by TLC; after completion of the reaction, the volatiles were removed in vacuo to obtain the crude. The crude was purified through column chromatography using 30% EtOAc/ hexanes to afford compound 58 (600 mg, 51%) as an off white solid. TLC: 40% EtOAc/ hexanes (R 0.3); LC-MS: 81.5 1%; 294.9(M+1) (column; Kinetex EVO C-18 (50 x 3.0 mm, 2.6 um); RT 2.27 mm. 2.5 mM NH400CH in water + 5% ACN: ACN + 5% 2.5 mM NH400CH in water, 0.8 mL/min).

Reference： [1]Current Patent Assignee: ASSEMBLY BIOSCIENCES, INC. - WO2018/53157, 2018, A1 Location in patent: Page/Page column 77; 78

37
[ 1370008-65-3 ]
tert-butyl ((2-chlorothiazol-5-yl)methyl)carbamate [ No CAS ]
tert-butyl ((2-(3-oxocyclopentyl)thiazol-5-yl)methyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate / water; 1,2-dimethoxyethane / 16 h / 120 °C / Sealed tube; Inert atmosphere 2: palladium 10% on activated carbon; hydrogen / methanol / 16 h / 20 °C

Reference： [1]Current Patent Assignee: ASSEMBLY BIOSCIENCES, INC. - WO2018/53157, 2018, A1

38
[ 1370008-65-3 ]
[ 1370008-71-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: potassium phosphate / bis-triphenylphosphine-palladium(II) chloride / 1,4-dioxane; water / 12 h / 80 °C 2.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -78 °C 2.2: 2 h / -78 °C 3.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 16 h / 0 - 20 °C 4.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 16 h / 0 - 20 °C 5.1: dimethylsulfide borane complex / tetrahydrofuran / 1 h / 0 °C

Reference： [1]Current Patent Assignee: Wang, Zhong; Smith, Emilie D.; Veal, James M.; Huang, Kenneth H.; Atkinson, Robert N.; Jiang, Rong - US2012/77814, 2012, A1

39
[ 1370008-65-3 ]
[ 1370008-72-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: potassium phosphate / bis-triphenylphosphine-palladium(II) chloride / 1,4-dioxane; water / 12 h / 80 °C 2.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -78 °C 2.2: 2 h / -78 °C 3.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 16 h / 0 - 20 °C 4.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 16 h / 0 - 20 °C 5.1: dimethylsulfide borane complex / tetrahydrofuran / 1 h / 0 °C

Reference： [1]Current Patent Assignee: Wang, Zhong; Smith, Emilie D.; Veal, James M.; Huang, Kenneth H.; Atkinson, Robert N.; Jiang, Rong - US2012/77814, 2012, A1

40
[ 1370008-65-3 ]
[ 1370008-75-5 ]
[ 1370008-74-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: potassium phosphate / bis-triphenylphosphine-palladium(II) chloride / 1,4-dioxane; water / 12 h / 80 °C 2.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -78 °C 2.2: 2 h / -78 °C 3.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 16 h / 0 - 20 °C 4.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 16 h / 0 - 20 °C 5.1: dimethylsulfide borane complex / tetrahydrofuran / 1 h / 0 °C 6.1: hydrogen / {Rh[(R,R)-Me-Duphos](COD)}BF₄ / dichloromethane / 16 h 7.1: triethylamine / dichloromethane / 2 h / 0 - 20 °C

Reference： [1]Current Patent Assignee: Wang, Zhong; Smith, Emilie D.; Veal, James M.; Huang, Kenneth H.; Atkinson, Robert N.; Jiang, Rong - US2012/77814, 2012, A1

41
[ 1241789-62-7 ]
[ 73183-34-3 ]
[ 1370008-65-3 ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate at 100℃; for 1h; Inert atmosphere;	162.2 Step 2: 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclopent-2-enone A solution of 3-oxocyclopent-1-en-1-yl trifluoromethanesulfonate (2.5 g, 10.86 mmol) in dioxane (50 mL) was added 4,4,5,5-tetramethyl-2-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane (5.5 g, 21.65 mmol), Pd(dppf)Cl2 (720 mg, 0.98 mmol), KOAc (2.1 g, 21.39 mmol). The resultant solution was stirred for 1 h at 100° C. under nitrogen. The solution was cooled to room temperature, diluted with water and extracted with dichloromethane. The collected organic was dried over Na2SO4, filtered, and concentrated under vacuum. The residue was purified by a silica-gel column eluted with PE/EA (10/1) to afford 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclopent-2-enone (2 g, crude product) as a yellow oil. LCMS (ESI): [M+H]+=127.1.

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - US2018/282328, 2018, A1 Location in patent: Paragraph 1711; 1712

42
[ 1370008-65-3 ]
N-[8-amino-5-bromo-6-(4-methylpyridin-3-yl)-2,7-naphthyridin-3-yl]cyclopropanecarboxamide [ No CAS ]
N-[8-amino-6-(4-methylpyridin-3-yl)-5-(3-oxocyclopent-1-en-1-yl)-2,7-naphthyridin-3-yl]cyclopropanecarboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate In 1,4-dioxane; water at 100℃; for 6h; Inert atmosphere;	162.3 Step 3: N-(8-amino-6-(4-methylpyridin-3-yl)-5-(3-oxocyclopent-i -enyl)-2,7-naphthyridin-3-yl)cyclo- propanecarboxamide A solution of N-[8-amino-5-bromo-6-(4-methylpyridin-3-yl)-2,7-naphthyridin-3-yl]cyclopropanecarboxamide (500 mg, 1.25 mmol) in dioxane (10 mL)/water (2 mL) was added to a mixture of 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclopent-2-enone (320 mg, 2.54 mmol), Pd(dppf)Cl2 (280 mg, 0.38 mmol), and sodium bicarbonate (220 mg, 2.61 mmol). The mixture was stirred 100 OC under nitrogen. After 6 h, the reaction mixture was concentrated. The residue was purified with silica gel chromatography eluted with DCM/MeOH (10:1). This resulted in N-[8-amino-6-(4-methylpyridin-3-yl)-5-(3-oxocyclopent-1-en-1-yl)-2,7-naphthyridin-3-yl]cyclopropanecarboxamide (200 mg, 40%) as a yellow solid. LCMS (ESI): [M+H]+=400.1.

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - US2018/282328, 2018, A1 Location in patent: Paragraph 1713; 1714

43
[ 1370008-65-3 ]
N-[8-amino-5-bromo-6-(4-methylpyridin-3-yl)-2,7-naphthyridin-3-yl]cyclopropanecarboxamide [ No CAS ]
N-[8-amino-5-(3-hydroxycyclopent-1-en-1-yl)-6-(4-methylpyridin-3-yl)-2,7-naphthyridin-3-yl]cyclopropanecarboxamide [ 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 / water; 1,4-dioxane / 6 h / 100 °C / Inert atmosphere 2: sodium tetrahydroborate / methanol / 1 h / 20 °C

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - US2018/282328, 2018, A1

44
[ 1370008-65-3 ]
4-amino-6'-bromo-4'-methoxy-6-(thiazol-2-yl)-[2,2'-bipyridine]-3-carbonitrile [ No CAS ]
4-amino-4'-methoxy-6'-(3-oxocyclopent-1-en-1-yl)-6-(thiazol-2-yl)-[2,2'-dipyridine]-3-nitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
20%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; sodium carbonate In 1,4-dioxane; water at 120℃; for 3h; Inert atmosphere;	88.1 Example 88: Synthesis of Compounds 89 and 90 Step 1: 4-Amino-6'-bromo-4'-methoxy-6-(thiazol-2-yl)-[2,2'-dipyridine]_3-carbonitrile (78 mg, 0.20 mmol) , 3_(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclopent-2-en-1-one (50 mg, 0.24 mmol) , [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride dichloromethane complex (16 mg, 0.02 mmol), saturatedA mixture of sodium carbonate aqueous solution (0.6 mL) in 1,4-dioxane (10.0 mL) was stirred for 3 hours under nitrogen atmosphere at 120 ° C, concentrated under reduced pressure and flash chromatography (methylene chloride / methanol = 100 / 1) Purification of 4-amino-4'-methoxy-6'-(3-oxocyclopent-1-en-1-yl)-6-(thiazol-2-yl)_[2,2' _Dipyridine]-3-carbonitrile (Compound 89, 15 mg, Yield: 20%) was obtained as a pale yellow solid.

Reference： [1]Current Patent Assignee: SHENZHEN LANGRUN INVESTMENT CO., LTD. - CN109651358, 2019, A Location in patent: Paragraph 0528; 0529

45
[ 1370008-65-3 ]
4-amino-6'-bromo-4'-methoxy-6-(thiazol-2-yl)-[2,2'-bipyridine]-3-carbonitrile [ No CAS ]
4-amino-6'-(3-hydroxycyclopent-1-en-1-yl)-4'-methoxy-6-(thiazol-2-yl)-[2,2'-dipyridine]-3-nitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; sodium carbonate / 1,4-dioxane; water / 3 h / 120 °C / Inert atmosphere 2: sodium tetrahydroborate / tetrahydrofuran; methanol / 1 h / 0 °C

Reference： [1]Current Patent Assignee: SHENZHEN LANGRUN INVESTMENT CO., LTD. - CN109651358, 2019, A

46
[ 1370008-65-3 ]
tert-butyl 5-(3-hydroxycyclopentyl)-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / 1,4-dioxane / 16 h / 100 °C / Inert atmosphere 2: nickel(II) chloride hexahydrate; methanol; sodium tetrahydroborate / 0.17 h / 0 - 20 °C

Reference： [1]Current Patent Assignee: BIOCON LIMITED; BRISTOL-MYERS SQUIBB CO - US2019/185469, 2019, A1

47
[ 1370008-65-3 ]
tert-butyl 3-isopropyl-5-(3-oxocyclopentyl)-1H-pyrrolo[3,2-b]pyridine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / 1,4-dioxane / 16 h / 100 °C / Inert atmosphere 2: nickel(II) chloride hexahydrate; methanol; sodium tetrahydroborate / 0.17 h / 0 - 20 °C 3: Dess-Martin periodane / dichloromethane / 16 h / 0 - 20 °C

Reference： [1]Current Patent Assignee: BIOCON LIMITED; BRISTOL-MYERS SQUIBB CO - US2019/185469, 2019, A1

48
[ 1370008-65-3 ]
3-isopropyl-5-(1,4-dioxaspiro[4.4]nonan-7-yl)-1H-pyrrolo[3,2-b]pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / 1,4-dioxane / 16 h / 100 °C / Inert atmosphere 2: nickel(II) chloride hexahydrate; methanol; sodium tetrahydroborate / 0.17 h / 0 - 20 °C 3: Dess-Martin periodane / dichloromethane / 16 h / 0 - 20 °C 4: toluene-4-sulfonic acid / toluene / 16 h / 130 °C

Reference： [1]Current Patent Assignee: BIOCON LIMITED; BRISTOL-MYERS SQUIBB CO - US2019/185469, 2019, A1

49
[ 1370008-65-3 ]
tert-butyl 3-isopropyl-5-(1,4-dioxaspiro[4.4]nonan-7-yl)-1H-pyrrolo[3,2-b]pyridine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / 1,4-dioxane / 16 h / 100 °C / Inert atmosphere 2: nickel(II) chloride hexahydrate; methanol; sodium tetrahydroborate / 0.17 h / 0 - 20 °C 3: Dess-Martin periodane / dichloromethane / 16 h / 0 - 20 °C 4: toluene-4-sulfonic acid / toluene / 16 h / 130 °C 5: dmap; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 3 h / 20 °C

Reference： [1]Current Patent Assignee: BIOCON LIMITED; BRISTOL-MYERS SQUIBB CO - US2019/185469, 2019, A1

50
[ 1370008-65-3 ]
tert-butyl 3-isopropyl-5-(1,4-dioxaspiro[4.4]nonan-7-yl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[3,2-b]pyridine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / 1,4-dioxane / 16 h / 100 °C / Inert atmosphere 2.1: nickel(II) chloride hexahydrate; methanol; sodium tetrahydroborate / 0.17 h / 0 - 20 °C 3.1: Dess-Martin periodane / dichloromethane / 16 h / 0 - 20 °C 4.1: toluene-4-sulfonic acid / toluene / 16 h / 130 °C 5.1: dmap; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 3 h / 20 °C 6.1: lithium diisopropyl amide / tetrahydrofuran / 2 h / -78 °C 6.2: -78 - 20 °C

Reference： [1]Current Patent Assignee: BIOCON LIMITED; BRISTOL-MYERS SQUIBB CO - US2019/185469, 2019, A1

51
[ 1370008-65-3 ]
tert-butyl 3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(1,4-dioxaspiro[4.4]nonan-7-yl)-1H-pyrrolo[3,2-b]pyridine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)CH₂Cl₂ / 1,4-dioxane / 16 h / 100 °C / Inert atmosphere 2.1: nickel(II) chloride hexahydrate; methanol; sodium tetrahydroborate / 0.17 h / 0 - 20 °C 3.1: Dess-Martin periodane / dichloromethane / 16 h / 0 - 20 °C 4.1: toluene-4-sulfonic acid / toluene / 16 h / 130 °C 5.1: dmap; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 3 h / 20 °C 6.1: lithium diisopropyl amide / tetrahydrofuran / 2 h / -78 °C 6.2: -78 - 20 °C 7.1: potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)CH₂Cl₂ / water; 1,4-dioxane / 16 h / 100 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: BIOCON LIMITED; BRISTOL-MYERS SQUIBB CO - US2019/185469, 2019, A1

52
[ 1370008-65-3 ]
3-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)cyclopentan-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 8 steps 1.1: potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)CH₂Cl₂ / 1,4-dioxane / 16 h / 100 °C / Inert atmosphere 2.1: nickel(II) chloride hexahydrate; methanol; sodium tetrahydroborate / 0.17 h / 0 - 20 °C 3.1: Dess-Martin periodane / dichloromethane / 16 h / 0 - 20 °C 4.1: toluene-4-sulfonic acid / toluene / 16 h / 130 °C 5.1: dmap; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 3 h / 20 °C 6.1: lithium diisopropyl amide / tetrahydrofuran / 2 h / -78 °C 6.2: -78 - 20 °C 7.1: potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)CH₂Cl₂ / water; 1,4-dioxane / 16 h / 100 °C / Inert atmosphere 8.1: trifluoroacetic acid / dichloromethane / 16 h / 20 °C

Reference： [1]Current Patent Assignee: BIOCON LIMITED; BRISTOL-MYERS SQUIBB CO - US2019/185469, 2019, A1

53
[ 1370008-65-3 ]
cis-3-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)cyclopentan-1-amine [ No CAS ]
3-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)cyclopentan-1-amine [ No CAS ]
trans-3-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)cyclopentan-1-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 9 steps 1.1: potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)CH₂Cl₂ / 1,4-dioxane / 16 h / 100 °C / Inert atmosphere 2.1: nickel(II) chloride hexahydrate; methanol; sodium tetrahydroborate / 0.17 h / 0 - 20 °C 3.1: Dess-Martin periodane / dichloromethane / 16 h / 0 - 20 °C 4.1: toluene-4-sulfonic acid / toluene / 16 h / 130 °C 5.1: dmap; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 3 h / 20 °C 6.1: lithium diisopropyl amide / tetrahydrofuran / 2 h / -78 °C 6.2: -78 - 20 °C 7.1: potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)CH₂Cl₂ / water; 1,4-dioxane / 16 h / 100 °C / Inert atmosphere 8.1: trifluoroacetic acid / dichloromethane / 16 h / 20 °C 9.1: acetic acid; ammonium acetate; ammonium chloride / tetrahydrofuran; N,N-dimethyl-formamide / 16 h / 20 °C 9.2: 2 h / 20 °C

Reference： [1]Current Patent Assignee: BIOCON LIMITED; BRISTOL-MYERS SQUIBB CO - US2019/185469, 2019, A1

54
[ 1370008-65-3 ]
tert-butyl 5-bromo-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate [ No CAS ]
tert-butyl 3-isopropyl-5-(3-oxocyclopent-1-en-1-yl)-1H-pyrrolo[3,2-b]pyridine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ In 1,4-dioxane at 100℃; for 16h; Inert atmosphere;	7-9 Intermediate 7D: tert-butyl 3-isopropyl-5-(3-oxocyclopent-1-en-1-yl)-1H-pyrrolo[3,2-b]pyridine-1-carboxylate To a stirred solution of tert-butyl 5-bromo-3-isopropyl-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (16 g, 47.2 mmol) in dioxane (400 mL) were added 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclopent-2-en-1-one (14.72 g, 70.7 mmol) and potassium phosphate tribasic (20.02 g, 94 mmol). The reaction mixture was degassed with nitrogen for 10 min, and then PdCl2(dppf)-CH2Cl2 adduct (3.85 g, 4.72 mmol) was added. The reaction mixture was stirred at 100° C. for 16 h. The reaction mass was filtered through a Celite bed, washed with EtOAc and concentrated to get crude product. The crude product was purified by silica gel column chromatography, the fractions were collected and concentrated to afford tert-butyl 3-isopropyl-5-(3-oxocyclopent-1-en-1-yl)-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (15 g, 44.1 mmol, 93% yield) as a brown solid. LCMS retention time 1.76 min [L]. MS m/z: 341.6 (M+H).

Reference： [1]Current Patent Assignee: BIOCON LIMITED; BRISTOL-MYERS SQUIBB CO - US2019/185469, 2019, A1 Location in patent: Paragraph 0568-0569

55
[ 1370008-65-3 ]
2-(4-bromo-3-methoxyphenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole [ No CAS ]
3-(2-methoxy-4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)phenyl)cyclopent-2-enone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66.7%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate In 1,4-dioxane; water at 90℃; Inert atmosphere;	3-(2-Methoxy-4-(l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazol-2- yl)phenyl)cyclopent-2-enone. To a solution of 2-(4-bromo-3-methoxyphenyl)-l-((2- (trimethylsilyl)ethoxy)methyl)-lH-imidazole (1.5 g, 3.9 mmol) in dioxane/LLO (60 mL, v/v=5: l) was added 3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)cyclopent-2-en-l-one (1.0 g, 4.7 mmol), Pd(dppf)Cl2 (500.0 mg, 0.4 mmol) and K3PO4 (2.1 g, 9.8 mmol). The reaction was stirred at 90°C under an N2 atmosphere overnight. The solvent was removed, water added, and the mixture extracted with EtOAc (50 mL x 3). The combined organic layers were dried over NaiSOr and concentrated to give the crude product, which was purified by silica gel column chromatography using 10: 1 petroleum ether/ethyl acetate to afford 3-(2-methoxy-4-(l-((2- (trimethylsilyl)ethoxy)methyl)-lH-imidazol-2-yl)phenyl)cyclopent-2-enone (1.0 g, 66.7%) as a gray solid. MS Calcd.: 384.2, MS Found: 385.3 [M + 1] +.

Reference： [1]Current Patent Assignee: ASSEMBLY BIOSCIENCES, INC. - WO2020/86533, 2020, A1 Location in patent: Page/Page column 92; 93

56
[ 1370008-65-3 ]
3-(1-methyl-1H-pyrazol-4-yl)cyclopentanone [ No CAS ]

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

Reference： [1]Current Patent Assignee: ASSEMBLY BIOSCIENCES, INC. - WO2020/86533, 2020, A1

57
[ 1370008-65-3 ]
3-(1-methyl-1H-pyrazol-4-yl)cyclopent-1-enyl trifluoromethanesulfonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; 1,4-dioxane / 80 °C / Inert atmosphere 2.1: palladium 10% on activated carbon; hydrogen / ethanol / 80 °C 3.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -78 °C 3.2: 4 h / 30 °C

Reference： [1]Current Patent Assignee: ASSEMBLY BIOSCIENCES, INC. - WO2020/86533, 2020, A1

58
[ 1370008-65-3 ]
1-methyl-4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclopent-2-enyl)-1H-pyrazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; 1,4-dioxane / 80 °C / Inert atmosphere 2.1: palladium 10% on activated carbon; hydrogen / ethanol / 80 °C 3.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -78 °C 3.2: 4 h / 30 °C 4.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 4 h / 80 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: ASSEMBLY BIOSCIENCES, INC. - WO2020/86533, 2020, A1

59
[ 1370008-65-3 ]
5-amino-N-(3-chloro-4-fluorophenyl)-1-methyl-3-(3-(1-methyl-1H- pyrazol-4-yl)cyclopent-1-enyl)-1H-pyrazole-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; 1,4-dioxane / 80 °C / Inert atmosphere 2.1: palladium 10% on activated carbon; hydrogen / ethanol / 80 °C 3.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -78 °C 3.2: 4 h / 30 °C 4.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 4 h / 80 °C / Inert atmosphere 5.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; 1,4-dioxane / 2 h / 95 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: ASSEMBLY BIOSCIENCES, INC. - WO2020/86533, 2020, A1

60
[ 1370008-65-3 ]
5-amino-N-(3-chloro-4-fluorophenyl)-1-methyl-3-(3-(1-methyl-1H-pyrazol-4-yl)cyclopentyl)-1H-pyrazole-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; 1,4-dioxane / 80 °C / Inert atmosphere 2.1: palladium 10% on activated carbon; hydrogen / ethanol / 80 °C 3.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -78 °C 3.2: 4 h / 30 °C 4.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 4 h / 80 °C / Inert atmosphere 5.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / water; 1,4-dioxane / 2 h / 95 °C / Inert atmosphere 6.1: hydrogen; Wilkinson's catalyst / methanol / 60 °C / 7600.51 Torr

Reference： [1]Current Patent Assignee: ASSEMBLY BIOSCIENCES, INC. - WO2020/86533, 2020, A1

61
[ 15803-02-8 ]
[ 1370008-65-3 ]
[ 1243190-98-8 ]

Yield	Reaction Conditions	Operation in experiment
46%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate In 1,4-dioxane; water at 80℃; Inert atmosphere;	3-(l-Methyl-lH-pyrazol-4-yl)cyclopent-2-en-l-one. A mixture of 3-(4, 4,5,5- tetramethyl-l,3,2-dioxaborolan-2-yl)cyclopent-2-en-l-one (5.0 g, 24.0 mmol), 4-bromo-l- methyl-lH-pyrazole (3.9 g, 24.0 mmol), K3PO4 (10.2 mg, 48.0 mmol) and Pd(dppf)Ch (880 mg, 1.2 mmol) in dioxane (80 mL) and H2O (20 mL) was stirred at 80 °C overnight under an N2 atmosphere. The solvent was removed under vacuum and the residue was purified by silica gel column chromatography using 1:9 petroleum ether/ethyl acetate to afford 3-(l-methyl-lH- pyrazol-4-yl)cyclopent-2-en-l-one (1.8 g, 46% yield) as a yellow solid. MS Calcd.: 162.1, MS Found: 163.4 [M+l]+.

Reference： [1]Current Patent Assignee: ASSEMBLY BIOSCIENCES, INC. - WO2020/86533, 2020, A1 Location in patent: Page/Page column 55

62
[ 1370008-65-3 ]
[ 19524-06-2 ]
3-(pyridin-4-yl)cyclopent-2-en-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73.26%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate In 1,4-dioxane; water at 80℃; for 16h; Inert atmosphere;	3-(Pyridin-4-yl)cyclopent-2-en-l-one. To a solution of 4-bromopyridine (2 g, 10.29 mmol, 1 eq, HC1) in dioxane (30 mL) and H2O (6 mL) was added 3-(4,4,5,5- tetramethyl-l,3,2- dioxaborolan-2-yl)cyclopent-2-en-l-one (3.21 g, 15.43 mmol, 1.5 eq), Pd(dppf)Cl2 (752.56 mg, 1.03 mmol, 0.1 eq) and K3PO4 (6.55 g, 30.87 mmol, 3 eq). The suspension was degassed and purged with N2 3 times. The mixture was stirred under N2 at 80 °C for 16 hr. The reaction mixture was filtered, and the filtrate diluted with water (20 mL) and extracted with EtOAc (30 mL x 3). The combined organic layers were washed with brine (15 mL x 2), dried over Na2S04, filtered and concentrated under reduced pressure to give a residue, which was purified by flash silica gel chromatography (ISCO; 40 g SepaFlash Silica Flash Column, Eluent of 0-100% Ethyl acetate/Petroleum ether gradient 40 mL/min) to give 3-(4-pyridyl)cyclopent-2-en-l-one (1.2 g, 7.54 mmol, 73.26% yield), as a yellow solid. NMR (400 MHz, CHLOROFORM-d) d 2.52-2.67 (m, 2H), 3.00 (dt, J=4.85, 2.21 Hz, 2H), 6.65 (d, J=l.76 Hz, 1H), 7.40-7.47 (m, 2H), 8.69 (br d, J=4.4l Hz, 2H).

Reference： [1]Current Patent Assignee: ASSEMBLY BIOSCIENCES, INC. - WO2020/86533, 2020, A1 Location in patent: Page/Page column 65; 66

63
[ 1370008-65-3 ]
tert-butyl 1-(5-methyl-2-(3-oxocyclopentyl)phenoxy)cyclopropane-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: potassium phosphate / 1,4-dioxane; water / 0.25 h / Inert atmosphere 1.2: 16 h / 100 °C / Inert atmosphere 2.1: hydrogen; palladium 10% on activated carbon / ethyl acetate / 16 h / 20 °C / 2585.81 Torr
	Multi-step reaction with 3 steps 1.1: potassium phosphate / 1,4-dioxane; water / 0.25 h / Inert atmosphere 1.2: 16 h / 100 °C / Inert atmosphere 2.1: hydrogen; palladium 10% on activated carbon / ethyl acetate / 16 h / 20 °C / 2585.81 Torr 3.1: pyridinium chlorochromate / dichloromethane / 4 h / 0 - 20 °C

Reference： [1]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - WO2020/128768, 2020, A1
[2]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - WO2020/128768, 2020, A1

64
[ 1370008-65-3 ]
tert-butyl 1-(2-(3-hydroxycyclopentyl)-5-methylphenoxy)cyclopropane-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: potassium phosphate / 1,4-dioxane; water / 0.25 h / Inert atmosphere 1.2: 16 h / 100 °C / Inert atmosphere 2.1: hydrogen; palladium 10% on activated carbon / ethyl acetate / 16 h / 20 °C / 2585.81 Torr

Reference： [1]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - WO2020/128768, 2020, A1

65
[ 1370008-65-3 ]
tert-butyl 1-(2-(3,3-difluorocyclopentyl)-5-methylphenoxy)cyclopropane-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: potassium phosphate / 1,4-dioxane; water / 0.25 h / Inert atmosphere 1.2: 16 h / 100 °C / Inert atmosphere 2.1: hydrogen; palladium 10% on activated carbon / ethyl acetate / 16 h / 20 °C / 2585.81 Torr 3.1: diethylamino-sulfur trifluoride / dichloromethane / 16 h / 0 - 20 °C / Inert atmosphere
	Multi-step reaction with 4 steps 1.1: potassium phosphate / 1,4-dioxane; water / 0.25 h / Inert atmosphere 1.2: 16 h / 100 °C / Inert atmosphere 2.1: hydrogen; palladium 10% on activated carbon / ethyl acetate / 16 h / 20 °C / 2585.81 Torr 3.1: pyridinium chlorochromate / dichloromethane / 4 h / 0 - 20 °C 4.1: diethylamino-sulfur trifluoride / dichloromethane / 16 h / 0 - 20 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - WO2020/128768, 2020, A1
[2]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - WO2020/128768, 2020, A1

66
[ 1370008-65-3 ]
1-(2-(3,3-difluorocyclopentyl)-5-methylphenoxy)cyclopropane-1-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: potassium phosphate / 1,4-dioxane; water / 0.25 h / Inert atmosphere 1.2: 16 h / 100 °C / Inert atmosphere 2.1: hydrogen; palladium 10% on activated carbon / ethyl acetate / 16 h / 20 °C / 2585.81 Torr 3.1: diethylamino-sulfur trifluoride / dichloromethane / 16 h / 0 - 20 °C / Inert atmosphere 4.1: hydrogenchloride / 1,4-dioxane / 16 h / 20 °C
	Multi-step reaction with 5 steps 1.1: potassium phosphate / 1,4-dioxane; water / 0.25 h / Inert atmosphere 1.2: 16 h / 100 °C / Inert atmosphere 2.1: hydrogen; palladium 10% on activated carbon / ethyl acetate / 16 h / 20 °C / 2585.81 Torr 3.1: pyridinium chlorochromate / dichloromethane / 4 h / 0 - 20 °C 4.1: diethylamino-sulfur trifluoride / dichloromethane / 16 h / 0 - 20 °C / Inert atmosphere 5.1: hydrogenchloride / 1,4-dioxane / 16 h / 20 °C

Reference： [1]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - WO2020/128768, 2020, A1
[2]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - WO2020/128768, 2020, A1

67
[ 1370008-65-3 ]
1-(2-(3,3-difluorocyclopentyl)-5-methylphenoxy)-N-((6-fluoropyridin-2-yl)sulfonyl)cyclopropane-1-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: potassium phosphate / 1,4-dioxane; water / 0.25 h / Inert atmosphere 1.2: 16 h / 100 °C / Inert atmosphere 2.1: hydrogen; palladium 10% on activated carbon / ethyl acetate / 16 h / 20 °C / 2585.81 Torr 3.1: diethylamino-sulfur trifluoride / dichloromethane / 16 h / 0 - 20 °C / Inert atmosphere 4.1: hydrogenchloride / 1,4-dioxane / 16 h / 20 °C 5.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; dmap / dichloromethane / 16 h / 0 - 20 °C
	Multi-step reaction with 6 steps 1.1: potassium phosphate / 1,4-dioxane; water / 0.25 h / Inert atmosphere 1.2: 16 h / 100 °C / Inert atmosphere 2.1: hydrogen; palladium 10% on activated carbon / ethyl acetate / 16 h / 20 °C / 2585.81 Torr 3.1: pyridinium chlorochromate / dichloromethane / 4 h / 0 - 20 °C 4.1: diethylamino-sulfur trifluoride / dichloromethane / 16 h / 0 - 20 °C / Inert atmosphere 5.1: hydrogenchloride / 1,4-dioxane / 16 h / 20 °C 6.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; dmap / dichloromethane / 16 h / 0 - 20 °C

Reference： [1]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - WO2020/128768, 2020, A1
[2]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - WO2020/128768, 2020, A1

68
[ 1370008-65-3 ]
tert-butyl 1-(2-bromo-5-methylphenoxy)cyclopropanecarboxylate [ No CAS ]
tert-butyl 1-(5-methyl-2-(3-oxocyclopent-1-en-1-yl)phenoxy)cyclopropane-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
54%	Stage #1: 3‐(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclopent-2-ene-1-one; tert-butyl 1-(2-bromo-5-methylphenoxy)cyclopropanecarboxylate With potassium phosphate In 1,4-dioxane; water for 0.25h; Inert atmosphere; Stage #2: With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ In 1,4-dioxane; water at 100℃; for 16h; Inert atmosphere;	3 Step 3: The stirred solution of ferf-butyl 1 -(2-bromo-5-methylphenoxy)cyclopropane-1 - carboxylate (I 6-1) (2 2 g, 6.723 mmol), 3-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2- y)cyclopeni-2-en-1 -one (2.1 g, 10.1 mmol), K3P04 (2.9 g, 13.4 mmol) in 4:1 v/v 1 ,4- dioxane/water (50 mL) was degassed with nitrogen for 15 min. Then PdCI2(dppf)-CH2Cl2 adduct (0.6 g, 0.7 mmol) was added, degassed and heated at 100 °C for 16 h under nitrogen. The reaction mixture was quenched with aqueous citric acid solution and extracted with EtOAc thrice. The combined organic solution was washed with brine, dried over anhydrous Na2S04 and concentrated in vacuo. The residue was purified on silica gel (EtOAc/hexane, 30-40%) to afford ferf-butyl 1 -(5-methyl-2-(3-oxocyclopent-1 -en-1 - yl)phenoxy)cyclopropane-1 -carboxylate (1 .2 g, 54% yield) as a pale yellow liquid: 1H NMR (400 MHz, CDCb) 6 7.41 (d, J= 7.6 Hz, 1 H), 6.87 - 6.82 (m, 3H), 3.Q7 - 3.Q4 (m, 2H), 2.49 - 2.47 (m, 2H), 2.37 (s, 3H), 1 .61 - 1 .57 (m, 2H), 1 .35 (s, 9H), 1 .29 - 1 .26 (m, 2H)

Reference： [1]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - WO2020/128768, 2020, A1 Location in patent: Page/Page column 218; 219

69
[ 1370008-65-3 ]
methyl 6-(cyclopropanecarboxamido)-3-(3-hydroxycyclopent-1-en-1-yl)picolinate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: chloro(2-dicyclohexylphosphino-2’,4’,6’-triisopropyl-1,1‘-biphenyl)[2-(2’-amino-1,1‘-biphenyl’)]palladium(II); potassium phosphate / 1,4-dioxane / 1 h / 80 °C / Inert atmosphere 2: sodium tetrahydroborate; cerium(III) chloride / methanol / 1 h / 20 °C

Reference： [1]Current Patent Assignee: NIMBUS THERAPEUTICS INC; CHARLES RIVER LABORATORIES INTERNATIONAL INC; NIMBUS SATURN - US2021/78996, 2021, A1

70
[ 1370008-65-3 ]
methyl 6-(cyclopropanecarboxamido)-3-(3-methoxycyclopentyl) picolinate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: chloro(2-dicyclohexylphosphino-2’,4’,6’-triisopropyl-1,1‘-biphenyl)[2-(2’-amino-1,1‘-biphenyl’)]palladium(II); potassium phosphate / 1,4-dioxane / 1 h / 80 °C / Inert atmosphere 2: sodium tetrahydroborate; cerium(III) chloride / methanol / 1 h / 20 °C 3: methanol; tetrahydrofuran / 3 h / 20 °C 4: hydrogen; palladium(II) hydroxide; ammonium formate / tetrahydrofuran / 20 °C / 1034.32 Torr

Reference： [1]Current Patent Assignee: NIMBUS THERAPEUTICS INC; CHARLES RIVER LABORATORIES INTERNATIONAL INC; NIMBUS SATURN - US2021/78996, 2021, A1

71
[ 1370008-65-3 ]
N-(6-(hydroxymethyl)-5-(3-methoxycyclopentyl)pyridin-2-yl) cyclopropane carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: chloro(2-dicyclohexylphosphino-2’,4’,6’-triisopropyl-1,1‘-biphenyl)[2-(2’-amino-1,1‘-biphenyl’)]palladium(II); potassium phosphate / 1,4-dioxane / 1 h / 80 °C / Inert atmosphere 2: sodium tetrahydroborate; cerium(III) chloride / methanol / 1 h / 20 °C 3: methanol; tetrahydrofuran / 3 h / 20 °C 4: hydrogen; palladium(II) hydroxide; ammonium formate / tetrahydrofuran / 20 °C / 1034.32 Torr 5: sodium tetrahydroborate / ethanol / 0.5 h / 70 °C

Reference： [1]Current Patent Assignee: NIMBUS THERAPEUTICS INC; CHARLES RIVER LABORATORIES INTERNATIONAL INC; NIMBUS SATURN - US2021/78996, 2021, A1

72
[ 1370008-65-3 ]
C₁₇H₂₀N₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: chloro(2-dicyclohexylphosphino-2’,4’,6’-triisopropyl-1,1‘-biphenyl)[2-(2’-amino-1,1‘-biphenyl’)]palladium(II); potassium phosphate / 1,4-dioxane / 1 h / 80 °C / Inert atmosphere 2: sodium tetrahydroborate; cerium(III) chloride / methanol / 1 h / 20 °C 3: methanol; tetrahydrofuran / 3 h / 20 °C

Reference： [1]Current Patent Assignee: NIMBUS THERAPEUTICS INC; CHARLES RIVER LABORATORIES INTERNATIONAL INC; NIMBUS SATURN - US2021/78996, 2021, A1

73
[ 1370008-65-3 ]
C₁₇H₂₄N₂O₅S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: chloro(2-dicyclohexylphosphino-2’,4’,6’-triisopropyl-1,1‘-biphenyl)[2-(2’-amino-1,1‘-biphenyl’)]palladium(II); potassium phosphate / 1,4-dioxane / 1 h / 80 °C / Inert atmosphere 2: sodium tetrahydroborate; cerium(III) chloride / methanol / 1 h / 20 °C 3: methanol; tetrahydrofuran / 3 h / 20 °C 4: hydrogen; palladium(II) hydroxide; ammonium formate / tetrahydrofuran / 20 °C / 1034.32 Torr 5: sodium tetrahydroborate / ethanol / 0.5 h / 70 °C 6: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.25 h / 20 °C

Reference： [1]Current Patent Assignee: NIMBUS THERAPEUTICS INC; CHARLES RIVER LABORATORIES INTERNATIONAL INC; NIMBUS SATURN - US2021/78996, 2021, A1

74
[ 1370008-65-3 ]
methyl 3-bromo-6-(cyclopropanecarboxamido)picolinate [ No CAS ]
methyl 6-(cyclopropanecarboxamido)-3-(3-oxocyclopent-1-en-1-yl)picolinate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With potassium phosphate; chloro(2-dicyclohexylphosphino-2’,4’,6’-triisopropyl-1,1‘-biphenyl)[2-(2’-amino-1,1‘-biphenyl’)]palladium(II) In 1,4-dioxane at 80℃; for 1h; Inert atmosphere;	Step-3 Step-3 Synthesis of methyl 6-(cyclopropanecarboxamido)-3-(3-oxocyclopent-1-en-1-yl)picolinate (Intermediate AA192-4) To a solution of Intermediate AA149-1 (1 g, 12.94 mmol) in dioxane (15 mL) was added potassium phosphate (2.2 g, 39.65 mmol, 3 eq) followed by dropwise addition of Intermediate AA192-3 (0.900 g, 40.55 mmol, 2.0 eq). After degassing with argon for 10 min, X-phose PdG2 (0.302 g, 32.74 mmol, 0.05 eq) was added. After stirring at 80° C. for 1 h, the reaction was diluted with water (500 mL) and extracted by ethyl acetate. The combined organic layer was washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by column chromatography (12-15% gradient of ethyl acetate in hexane) to afford Intermediate AA192-4 (0.820 g, 95%), MS (ES): m/z 300 [M+1]+

Reference： [1]Current Patent Assignee: NIMBUS THERAPEUTICS INC; CHARLES RIVER LABORATORIES INTERNATIONAL INC; NIMBUS SATURN - US2021/78996, 2021, A1 Location in patent: Paragraph 0979; 0983

75
[ 108-86-1 ]
[ 1370008-65-3 ]
[ 3810-26-2 ]

Yield	Reaction Conditions	Operation in experiment
48.9 mg	With potassium phosphate; palladium diacetate; XPhos In water; toluene at 80℃; for 18h;

Reference： [1]Gaube, Gregory; Leitch, David C.; Pipaon Fernandez, Nahiane [New Journal of Chemistry, 2021, vol. 45, # 43, p. 20095 - 20098]

76
[ 18766-96-6 ]
[ 73183-34-3 ]
[ 1370008-65-3 ]

Yield	Reaction Conditions	Operation in experiment
9 %Spectr.	With tris(o-methoxyphenyl)phosphine; palladium diacetate In water; acetone at 20℃; for 18h;

Reference： [1]Gaube, Gregory; Leitch, David C.; Pipaon Fernandez, Nahiane [New Journal of Chemistry, 2021, vol. 45, # 43, p. 20095 - 20098]

77
3-oxocyclopent-1-en-1-yl pivalate [ No CAS ]
[ 73183-34-3 ]
[ 1370008-65-3 ]

Yield	Reaction Conditions	Operation in experiment
62 %Spectr.	With tris(o-methoxyphenyl)phosphine; palladium diacetate In water; acetone at 20℃; for 18h;

Reference： [1]Gaube, Gregory; Leitch, David C.; Pipaon Fernandez, Nahiane [New Journal of Chemistry, 2021, vol. 45, # 43, p. 20095 - 20098]

78
[ 1370008-65-3 ]
(5-bromopyridin-3-yl)-(1,3-dimethylazetidin-3-yl)-(4-isopropylphenyl)methanol [ No CAS ]
3-{5-[(1,3-dimethylazetidin-3-yl)-hydroxy-(4-isopropylphenyl)methyl]pyridin-3-yl}-cyclopent-2-enone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
122 mg	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In acetonitrile at 80℃;	289.1 280. 1. (S)-(2-Cyclopent-1-enyl-pyridin-4-yl)-( 1, 3-dimethyl-azetidin-3-yl)-(4-isopropyl-phenyl)-methanol General procedure: To a solution of Example F1.5 (50mg) and cyclopentene-1-yl-boronic acid (16.1mg) in MeCN (0.5mL) were added Na2C03 (1M, 0.5mL) and Pd(PPh)3C (4.49mg), and the mixture was stirred for 3h30 at 80°C. The reaction mixture was cooled down to RT, diluted with MeOH, filtered off and purified by Prep LC-MS (V) to afford 30mg of the title compound as white solid. LC-MS (A): tR = 0.63min; [M+H]+: 377.33.

Reference： [1]Current Patent Assignee: IDORSIA PHARMACEUTICALS LTD - WO2021/219849, 2021, A1 Location in patent: Page/Page column 249; 252

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CAS No. :	1370008-65-3	MDL No. :	MFCD22683474
Formula :	C₁₁H₁₇BO₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	CGTGLMSBJLJNCL-UHFFFAOYSA-N
M.W :	208.06	Pubchem ID :	66822876
Synonyms :

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:

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P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 1370008-65-3 ] {[proInfo.proName]}

Quality Control of [ 1370008-65-3 ]

Related Doc. of [ 1370008-65-3 ]

Product Details of [ 1370008-65-3 ]

Safety of [ 1370008-65-3 ]

Application In Synthesis of [ 1370008-65-3 ]

[ 1370008-65-3 ] Synthesis Path-Downstream 1~78

Related Functional Groups of
[ 1370008-65-3 ]

Organoboron

Esters

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

[ CAS No. 1370008-65-3 ] {[proInfo.proName]}

Quality Control of [ 1370008-65-3 ]

Related Doc. of [ 1370008-65-3 ]

Product Details of [ 1370008-65-3 ]

Safety of [ 1370008-65-3 ]

Application In Synthesis of [ 1370008-65-3 ]

[ 1370008-65-3 ] Synthesis Path-Downstream 1~78

Related Functional Groups of [ 1370008-65-3 ]

Organoboron

Esters

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 1370008-65-3 ]