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[ CAS No. 286961-14-6 ] {[proInfo.proName]}

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Chemical Structure| 286961-14-6
Chemical Structure| 286961-14-6
Structure of 286961-14-6 * Storage: {[proInfo.prStorage]}
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Product Details of [ 286961-14-6 ]

CAS No. :286961-14-6 MDL No. :MFCD03840345
Formula : C16H28BNO4 Boiling Point : -
Linear Structure Formula :- InChI Key :VVDCRJGWILREQH-UHFFFAOYSA-N
M.W : 309.21 Pubchem ID :4642098
Synonyms :

Calculated chemistry of [ 286961-14-6 ]

Physicochemical Properties

Num. heavy atoms : 22
Num. arom. heavy atoms : 0
Fraction Csp3 : 0.81
Num. rotatable bonds : 4
Num. H-bond acceptors : 4.0
Num. H-bond donors : 0.0
Molar Refractivity : 91.9
TPSA : 48.0 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : Yes
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.52 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.0
Log Po/w (XLOGP3) : 2.34
Log Po/w (WLOGP) : 2.8
Log Po/w (MLOGP) : 1.54
Log Po/w (SILICOS-IT) : 1.18
Consensus Log Po/w : 1.57

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.97
Solubility : 0.333 mg/ml ; 0.00108 mol/l
Class : Soluble
Log S (Ali) : -2.99
Solubility : 0.318 mg/ml ; 0.00103 mol/l
Class : Soluble
Log S (SILICOS-IT) : -2.84
Solubility : 0.448 mg/ml ; 0.00145 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 0.0
Synthetic accessibility : 4.08

Safety of [ 286961-14-6 ]

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

Application In Synthesis of [ 286961-14-6 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 286961-14-6 ]

[ 286961-14-6 ] Synthesis Path-Downstream   1~25

  • 1
  • [ 166281-37-4 ]
  • [ 286961-14-6 ]
  • [ 947614-68-8 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate In N,N-dimethyl-formamide at 85℃; for 24.5h; 22.22a 2-Bromo-4,5-difluorophenol (2857 µl), N-Boc-1,2,3,6-tetrahydropyridine-4-boronic acid pinacol ester (7.73 g), potassium carbonate (10.36 g) and dichloro(1,1'-bis(diphenyl-phosphino)-ferrocene)palladium(II) DCM adduct (1.22 g) were dissolved in DMF (150 ml) in a dry apparatus under argon and the mixture was degassed by bubbling with argon for 30 min. The orange suspension was then heated under argon in an oil bath at 85 °C for 1 day to give a dark purple suspension. The reaction mixture was filtered through Celite and evaporated to dryness in vacuo. The crude product was purified by flash chromatography to yield pale green crystals.
Stage #1: 2-bromo-4,5-difluorophenol With triethylsilyl chloride; triethylamine In dichloromethane at 20℃; Stage #2: tert-Butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-1(2H)-pyridinecarboxylate With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; cesium fluoride In N,N-dimethyl-formamide at 110℃;
With potassium carbonate In N,N-dimethyl-formamide at 85℃; for 24h; 8.a 2-Bromo-4,5-difluorophenol (2857 µl), N-Boc-1,2,3,6-tetrahydropyridine-4-boronic acid pinacol ester (7.73 g), potassium carbonate (10.36 g) and dichloro(1,1'-bis(diphenylphosphino)-ferrocene)palladium(II) DCM adduct (1.22 g) were dissolved in DMF (150 ml) in a dry apparatus under argon and the mixture was degassed by bubbling with argon for 30 min. The orange suspension was then heated under argon in an oil bath at 85°C for 1 d to give a dark purple suspension. The reaction mixture was filtered through Celite and evaporated to dryness in vacuo. The crude product was purified by flash chromatography to yield pale green crystals.
  • 2
  • [ 1211536-93-4 ]
  • [ 286961-14-6 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
23% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate In 1,4-dioxane; water at 110℃; for 4h; Inert atmosphere; The synthesis of tert-butyl 4-(4-chloro-5H-pyrrolo[3,2-d]pyrimidin-6-yl)-5,6- dihydropyridine-1(2H)-carboxylate To a solution of aryl bromide (233 mg, 1.0 mmol) in 1,4- dioxane (8 mL) and H2O (2 mL) was added tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan- 2-yl)-5,6-dihyropyridine-1(2H)-carboxylate (Eunkyung, K. et al Bioorganic & Medicinal Chemistry Letters 2008, 18, 4993-4996) (245 mg, 0.8 mmol), Pd(dppf)Cl2.DCM (41 mg, 0.05 mmol) and K2CO3(276 mg, 2.0 mmol) under N2. The mixture was stirred at 110 °C for 4 h, cooled to rt, diluted with H2O (80 mL) and extracted with EtOAc (60 mL x 3 . The organic layers separated, dried (Na2SO4) concentrated in vacuo to afford a residue which was purified by column chromatography (petroleum ether/EtOAc = 5:1 to 2:1) to give the title compound (77 mg, yield 23%) as yellow solid ESI-MS (M+H)+: 335.2.1H NMR (400 MHz, CDCl3) : 10.82 (br, 1H), 8.71 (s, 1H), 6.73 (s, 1H), 6.68-6.56 (m, 1H), 4.16-4.13 (m, 2H), 3.70-3.65 (m, 2H), 2.62-2.60 (m, 2H), 1.46 (s, 9H).
  • 3
  • [ 1256584-75-4 ]
  • [ 286961-14-6 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
71% With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,4-dioxane; water at 110℃; for 1.5h; Inert atmosphere; Microwave irradiation; 23 Synthesis of 2-(2-(3-(1-acetyl-1,2,3,6-tetrahydropyridin-4-yl)-4-ethylphenyl) propan-2-yl)-1H-indole-6-carbonitrile (25) A mixture of 23 (350 mg, 0.68 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (422 mg, 1.36 mmol), Pd(PPh3)4 (158 mg, 0.136 mmol), and Na2CO3 (2 M in water, 1.5 mL) in dioxane (4.5 mL) was degassed with nitrogen for 5 min and then heated at 110 °C under microwave for 1.5 h. After the completion of the reaction, the mixture was diluted with EtOAc (20 mL) and filtered. The filtrate was concentrated and purified by chromatograph (petroleum/acetoacetate) to afford a yellow solid (275 mg, 71% yield): 1H NMR (300 MHz, CDCl3) δ 9.12 (s, 1H), 8.11 (d, J = 8.4 Hz, 1H), 7.69 (s, 1H), 7.41 (dd, J = 8.4, 1.2 Hz, 1H), 7.16-7.07 (m, 2H), 6.98-6.91 (m, 1H), 5.52-5.45 (m, 1H), 4.04-3.94 (m, 2H), 3.59 (t, J = 5.5 Hz, 2H), 2.57 (q, J = 7.5 Hz, 2H), 2.36-2.24 (m, 2H), 1.91 (s, 6H), 1.48 (s, 9H), 1.37 (s, 9H), 1.16 (t, J = 7.5 Hz, 3H). The obtained solid was dissolved in toluene/TFA (5 mL/5 mL). The mixture was heated at 80 °C for 3 h under nitrogen atmosphere. After being cooled to room temperature, the reaction mixture was evaporated in vacuum, and basified with saturated sodium bicarbonate until pH > 7. After extraction with EtOAc, the combined mixture was washed with brine, dried over sodium sulfate, and evaporated. The residue was purified by chromatograph (CHCl3/MeOH) to give the corresponding intermediate as a pale yellow solid (80 mg, 45%): 1H NMR (300 MHz, CDCl3 + CD3OD) δ 7.60-7.48 (m, 2H), 7.21 (d, J = 8.3 Hz, 1H), 7.10-6.99 (m, 2H), 6.94 (s, 1H), 6.42 (s, 1H), 5.53-5.43 (m, 1H), 3.40-3.30 (m, 2H), 2.96 (t, J = 5.6 Hz, 2H), 2.53 (q, J = 7.5 Hz, 2H), 2.21-2.10 (m, 2H), 1.70 (s, 6H), 1.11 (t, J = 7.5 Hz, 3H). The intermediate (80 mg, 0.22 mmol) was dissolved in 2 mL of pyridine. Ac2O (0.24 mL, 2.6 mmol) and DMAP (3 mg, 0.025 mmol) were added. The solution was stirred at room temperature overnight until the completion of the reaction. After removal of the solventunder vacuum, DCM (80 mL) was added and the solution was washed with diluted hydrochloric acid (1 N) followed by brine, dried over sodium sulfate, and then ltered. After evaporation of the solvent, the residue was puried by chromatograph (CHCl3/ MeOH) to yield the title product 25 as a white solid (81 mg, 91%yield) (29% overall yield in three steps): 1H NMR (300 MHz, CDCl3)d 8.51 (s, 1H), 7.60 (d, J 8.1Hz, 1H), 7.55 (s, 1H), 7.33e7.27 (m, 1H),7.18e7.05 (m, 2H), 6.97 (s, 1H), 6.51 (s, 1H), 5.60e5.43 (m, 1H),4.20e4.12 (m, 1H), 4.11e4.00 (m, 1H), 3.82-3.72 (m, 1H), 3.66-3.58 (m, 1H), 2.56 (q, J 7.5 Hz, 2H), 2.41-2.26 (m, 2H), 2.17-2.07 (m,3H), 1.76 (s, 6H), 1.17 (t, J 7.5 Hz, 3H). 13C NMR (126 MHz, CDCl3)d 169.6 and 169.4 (1C), 152.0, 144.4, 141.9, 139.6 and 139.5 (1C),138.8, 136.7, 134.9, 131.7, 128.7, 126.0 and 125.9 (1C), 125.5, 123.0 and 122.8 (1C), 121.3, 120.8, 115.2, 103.4, 99.7, 45.5 and 43.5 (1C),41.8 and 38.4 (1C), 39.7, 31.2 and 30.5 (1C), 29.7, 25.6, 22.0 and 21.6 (1C), 15.7. MS (EI) 411 (M). HRMS: calcd for C27H29N3O (M),411.2311; found 411.2313.
  • 4
  • [ 1211520-71-6 ]
  • [ 286961-14-6 ]
  • [ 1621519-76-3 ]
YieldReaction ConditionsOperation in experiment
42% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In 1,4-dioxane; water at 100℃; Inert atmosphere; Step 5:
tert-butyl 4-(5-bromo-4-methoxypyridin-2-yl)-5,6-dihydropyridin-1(2H)-carboxylate Step 5: tert-butyl 4-(5-bromo-4-methoxypyridin-2-yl)-5,6-dihydropyridin-1(2H)-carboxylate Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridin-1(2H)-carboxylate (3.09g, 10 mol), 2,5-dibromo-4-methoxypyridine (2.67 g, 10 mmol), Pd(PPh3)4 (578 mg, 0.5 mmol), and K2CO3 (3.34 g, 24 mmol) were added to 1,4-dioxane (50 mL) and water (10 mL) and purged with nitrogen. The resultant was stirred at 100°C overnight. After the resultant was cooled, it was purified by silica gel column chromatography to give tert-butyl 4-(5-bromo-4-methoxypyridin-2-yl)-5,6-dihydropyridin-1(2H)-carboxylate (1.55 g, 42% yield). MS m/z [ESI]: 369.1 [M+1]. 1H-NMR (400 MHz, CDCl3):δ= 8.49(s, 1H), 7.26 (s, 1H), 6.58 (s, 1H), 4.13 (t, 2H), 3.97 (s, 3H), 2.62 (d, 2H), 1.49 (s, 9H).
  • 5
  • [ 286961-14-6 ]
  • [ 1380575-45-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; potassium phosphate tribasic trihydrate; palladium diacetate / tetrahydrofuran / 85 °C / Inert atmosphere 2: 50% palladium on charcoal; hydrogen / methanol / 45 °C 3: hydrogenchloride / water / 2 h / 55 °C
  • 6
  • [ 1416712-39-4 ]
  • [ 286961-14-6 ]
  • [ 1954723-56-8 ]
YieldReaction ConditionsOperation in experiment
75% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate In 1,2-dimethoxyethane; water at 100℃; for 0.75h; Inert atmosphere; Step 1 - Synthesis of tert-butyl 4-(6-carbamoyl-3-fluoropyridin-2-yl)-5,6-dihydropyridine-1 (2H)-carboxylate (I-39) 6-bromo-5-fluoropicolinamide (I-38) (200 mg, 0.9 mmol) was combined with tert-butyl 4-(4, 4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1 (2H)-carboxylate (I-3) (310 mg) and Pd(dppf)CI2 (74.3 mg, 0.09 mmol) and cesium carbonate (892 mg, 2.74 mmol) and water (1 mL) and 1 ,2-dimethoxyethane (10ml_). The reaction mixture was degassed three times. After the reaction mixture was stirred at r.t. overnight and heated at 100°C for 45 mins, LCMS showed complete consumption of starting material. The reaction mixture was passed through Chem Elute and the column was washed with ethyl acetate. The eluent was concentrated and purified via 40 g column eluted with 0-100% EtOAc:heptanes to give tert-butyl 4-(6-carbamoyl-3-fluoropyridin-2-yl)-5,6-dihydropyridine-1 (2H)-carboxylate (I-39) (220 mg, 75%). 1H NMR (400 MHz, CDCIs) δ ppm 8.1 1 (dd, J = 8.34, 3.54 Hz, 1 H), 7.65 (br. s., 1 H), 7.49 - 7.59 (m, 1 H), 6.65 (br. s., 1 H), 5.57 (br. s., 1 H), 4.18 (d, J = 2.02 Hz, 2 H), 3.67 (t, J = 5.68 Hz, 2 H), 2.72 (br. s., 2 H), 1 .52 (s, 9 H).
  • 7
  • [ 286961-14-6 ]
  • [ 1496582-28-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate / water; 1,2-dimethoxyethane / 1 h / 110 °C / Inert atmosphere; Microwave irradiation 2: hydrogen; platinum(IV) oxide / 1 h
  • 8
  • [ 1286734-76-6 ]
  • [ 286961-14-6 ]
  • [ 2072805-16-2 ]
YieldReaction ConditionsOperation in experiment
83% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate In 1,4-dioxane; water at 90℃; for 5h; Inert atmosphere; D146 Description 0146tert-Butyl 4-(5-fl uoro-1 -(tetrahydro-2H-pyran-2-yI)-1 H-i ndazol-6-yl)-5,6-d i hyd ropyrid i neI (2H)-carboxylate (0146) A suspension of 6-bromo-5-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (5.0 g, 17 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1 (2H)-carboxylate (5.6 g, 18 mmol), Na2CO3 (4.6 g, 43 mmcl), Pd(dppf)C12 (622 mg, 0.850 mmcl) in dioxane (50 mL) and water (10 mL) was degassed with N2 for 3 times. The mixture was heated to 90°C and stirred for 5 hrs. The reaction mixture was cooled and the solvent was removed under vacuum. The residue was partitioned between water (200 mL) and EtOAc(100 mL). The organic layer was separated and the aqueous layer was extracted withEtOAc (100 mL x 2). The combined organic layers were washed with brine, dried overMgSO4 and concentrated. The crude was purified by column chromatography (PE: EtOAcfrom 20: ito 10: 1)to give the title compound (5.6 g, yield 83%) as an oily solid.1H NMR (300 MHz, CDCI3): ö 7.95 (s, IH), 7.40 (d, J 5.7 Hz, IH), 7.32 (d, J 10.5 Hz, 1H),5.96 (brs, 1H), 5.70-5.67 (m, 1H), 4.10-4.02 (m, 3H), 3.80-3.6i (m, 3H), 2.61-2.42 (m, 3H),2.21-2.03 (m, 2H), 1.82-1.63 (m, 3H), 1.50 (s, 9H).
  • 9
  • [ 286961-14-6 ]
  • [ 346688-38-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: XPhos Pd G2; 10% Pd/C; potassium phosphate / 1,4-dioxane; water / 4 h / 80 °C / Sealed tube; Inert atmosphere 1.2: 16 h / 18 °C 2.1: trifluoroacetic acid / dichloromethane / 4 h / 18 °C / Inert atmosphere 3.1: potassium carbonate / acetonitrile / 0.25 h / 18 °C / Inert atmosphere 3.2: 24 h / 0 - 70 °C / Inert atmosphere
  • 10
  • [ 1261216-28-7 ]
  • [ 286961-14-6 ]
  • [ 2168547-19-9 ]
YieldReaction ConditionsOperation in experiment
With tetrakis(triphenylphosphine) palladium(0); sodium hydrogencarbonate In 1,4-dioxane at 90℃; for 24h; Inert atmosphere; 1.1.2.1 Illustrative synthesis of mt 94 5-bromo-2-chloro-1-fluoro-3-methoxy-benzene (32g, 134 mmol, 1.0 eq) and tert-butyl4-(4,4,5,5-tetramethyl- 1,3 ,2-dioxaborolan-2-yl)-3 ,6-dihydro-2H-pyridine- 1 -carboxylate (41 .5g, 134 mmol, 1.0 eq) are stirred at room temperature in a mixture of dioxane (880 mL) and saturated aqueous NaHCO3 (250 mL), in a round bottom flask, and nitrogen is bubbled through the solution for 30 mi Pd(PPh3)4 (7.7g, 6.7 mmol, 0.05 eq) is then then added, and nitrogen is then bubbled through the solution for a few more mm, and the mixture is then heated at 90°C under nitrogen atmosphere. After 24 h, LC/MS analysis shows incomplete conversion. Pd(PPh3)4 (1 .5g) and boronic ester (1 .5g) are then newly added, and the mixture is stirred at 90°C for the weekend. Once complete conversion is observed by LC/MS analysis, the mixture is then cooled back at room temperature, and concentrated under reduced pressure. The residue obtained is then partitioned between DCM and water. The aqueous phase is extracted several times with DCM. The combined extracts are then dried and concentrated under reduced pressure to give crude expected compound that is then purified by flash chromatography (eluting with Heptane/AcOEt from 100/0 to 80/20), to finally afford pure expected compound. LCMS: MW (calcd): 341; m/z MW (obsd): 286-288 (M+H-tBu).
  • 11
  • [ 286961-14-6 ]
  • [ 2230198-02-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: caesium carbonate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane; water / 7 h / 90 °C / Inert atmosphere 2.1: platinum(IV) oxide; hydrogen / methanol / 3 h / 20 °C / 1551.49 Torr 3.1: tris-(dibenzylideneacetone)dipalladium(0); johnphos / 1,4-dioxane / 95 °C / Inert atmosphere 4.1: toluene-4-sulfonic acid / ethyl acetate / 2.25 h / 60 °C 5.1: toluene-4-sulfonic acid / acetonitrile / 2 h / 50 °C 5.2: 2 h 6.1: 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine / water / 20 °C
  • 12
  • [ 1427404-87-2 ]
  • [ 286961-14-6 ]
  • [ 2238831-35-9 ]
YieldReaction ConditionsOperation in experiment
750 mg With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate In 1,4-dioxane at 90℃; for 3h; Inert atmosphere; 10.1 Step 1 Preparation of tert-butyl 4-(pyrazolo[1 , 5-a]pyridin-4-yl)-3, 6-dihydropyridine- 1 (2H)-carboxylate 29. A mixture of 4-bromopyrazolo[1,5-a]pyridine (20) (502 mg, 2.55 mmol), tert-butyl4-(4,4,5, 5-tetramethyl- 1,3 ,2-dioxaborolan-2-yl)-3 ,6-dihydro-2H-pyridine- 1 -carboxylate (867 mg, 2.81 mmol) and 1,1 ‘-bi s(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex (208 mg, 0.25 5 mmol) in 1,4-dioxane (25 mL) was purged with nitrogen gas, followed by the addition of 2.5M K2C03 (3.1 mL) .The mixture was allowed to stir at 90 °C for 3 hours. The reaction was diluted with ethyl acetate, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The material was purified by silica gel column chromatography eluting with 30% ethyl acetate in hexane to provide product (29, 750 mg). [M+Hj = 300.2.
  • 14
  • [ 1260663-93-1 ]
  • [ 286961-14-6 ]
  • [ 2380196-39-2 ]
YieldReaction ConditionsOperation in experiment
122 mg With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate In 1,4-dioxane; water at 100℃; Inert atmosphere; Synthesis of 2-(3,4-dichlorobenzyl)-N-(1-methyl-1H-pyrazol-4-yl)-1-oxo-6-(piperidin-4-yl)-1,2-dihydro-2,7-naphthyridine-4-carboxamide (24) A mixture of S11 (300 mg, 1.67 mmol), S16a (517 mg, 1.67 mmol), Pd(dppf)Cl2 (122 mg, 0.167 mmol), Potassium acetate (328 mg, 3.34 mmol), 1,4-dioxane (1.5 ml) and water (0.4 mL) was stirred under an atmosphere of Argon at 100 °C overnight. The mixture was filtered and the filtrate evaporated under reduced pressure. The residue was purified by preparative TLC to afford tert-butyl 4-(8-oxo-7,8-dihydro-2,7-naphthyridin-3-yl)-3,6-dihydropyridine-1(2H)-carboxylate. (122 mg, 0.37 mmol). A suspension of tert-butyl 4-(8-oxo-7,8-dihydro-2,7-naphthyridin-3-yl)-3,6-dihydropyridine-1(2H)-carboxylate (122 mg, 0.37 mmol), triethylamine (53 μL, 0.37 mmol) and Pd/C 10% (12.2 mg) in MeOH (0.5 mL) was stirred under a balloon of hydrogen for 12 h. The mixture was filtered through a short plug of celite, washing with wet methanol. The filtrate and washings were concentrated under reduced pressure, diluted with water and extracted twice with DCM. The combined organics were washed with brine, dried over Na2SO4, filtered and evaporated under reduced pressure. The residue was purified by preparative TLC to afford S16 (70 mg, 0.21 mmol, 56% yield). According to GP6 S16 (70 mg, 0.21 mmol), N-bromosuccinimide (38 mg, 0.21 mmol) and DMF (1mL) afforded crude bromide product which was purified by preparative TLC to afford S17 (45 mg, 0.11 mmol, 50% yield). Alkylation according to GP2 using 1,2-dichloro-4-(chloromethyl)benzene (21.5 mg, 0.11 mmol), Cs2CO3 (43.0 mg, 0.13 mmol) and DMF (1mL) afforded S18 (35 mg, 0.06 mmol, 55% yield). A mixture of S18 (35 mg, 0.06 mmol), 1-methylpyrazol-4-amine (6 mg, 0.06 mmol), Pd(PPh3)Cl2 (4.4 mg, 0.006 mmol), Na2CO3 (13 mg, 0.12 mmol) and DMF (0.5 mL) was reacted according to GP5. Purification by preparative TLC afforded amide S19 (25 mg, 0.04 mmol, 65% yield). A mixture of S19 (25 mg, 0.04 mmol), methanol (1 mL) and a 4.0 M solution of HCL in 1,4-dioxane (1 mL) was stirred overnight at room temperature. Volatile components were removed under reduced pressure and the residue purified by preparative HPLC. Evaporation of fractions containing pure product afforded the title compound 24. White solid (8 mg, 0.20 mmol, 20% yield).1H NMR (DMSO-d6 ,400 MHz): δH 10.47 (s, 1 H), 9.33 (s, 1 H), 8.41 (s, 1 H), 8.06 (s, 1 H), 7.95 (s, 1 H), 7.70 (s, 1 H), 7.62 (d, J=8.2 Hz, 1 H), 7.52 (s, 1 H), 7.39 (d, J=7.2 Hz, 1 H), 5.21 (s, 2 H), 3.84 (s, 3 H), 3.02 - 3.16 (m, 2 H), 2.89 (app. t, J=1.0 Hz, 1 H), 2.68 (m, 2 H), 1.75 - 1.92 (m, 2 H), 1.54 - 1.72 (m, 2 H). LRMS (ESI) calculated for C25H24Cl2N6O2 [M+H]+ 511.14, found 511.28.
  • 15
  • [ 4422-32-6 ]
  • [ 375853-82-0 ]
  • tert-butyl 4-(3-(pyridin-3-yl)phenyl)-3,6-dihydropyridine-1(2H)-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
100% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,2-dimethoxyethane; water; at 120℃; for 0.75h;Sealed tube; Inert atmosphere; Microwave irradiation; General procedure: The boronic acid pinacol ester (1 equiv.), aryl halide (1 equiv.) and Pd(dppf)Cl2·CH2Cl2 adduct (0.1 equiv.) were dissolved in a mixture of DME and aqueous sodium carbonate (1M) in a microwave vial. The vial was sealed, evacuated and backfilled with N2. The reaction mixture was heated in the microwave at 120C for 45min and monitored by LCMS. The reaction mixture was concentrated in vacuo to give the crude material which was purified by Biotage column chromatography (see individual compounds for details of the eluent used).
  • 16
  • [ 1256276-41-1 ]
  • [ 286961-14-6 ]
  • [ 2351275-59-5 ]
YieldReaction ConditionsOperation in experiment
94% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate In tetrahydrofuran; water at 75℃; for 3h; Inert atmosphere; Sealed tube; 11 Intermediate 11B: tert-butyl 5-amino-3-fluoro-5′,6′-dihydro-[2,4′-bipyridine]-1′(2′H)-carboxylate General procedure: To a mixture containing 5-bromo-2-(3,4-dimethoxyphenyl)-3-methyl-1H-pyrrolo[3,2-b]pyridine (Intermediate 5A-1) and Intermediate 5A-2 (100 mg, 0.29 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1 (2H)-carboxylate (111 mg, 0.36 mmol), and Pd(dppf)C12 (10.5 mg, 0.014 mmol) in a screw cap vial was added THF (2.5 mL) followed by 3M aqueous solution of tripotassium phosphate (0.10 mL, 0.3 mmol). The vial was fitted with a Teflon lined septum cap. The system was evacuated under vacuum (via a needle from a nitrogen/vacuum manifold line) and backfilled with nitrogen gas. The procedure was repeated three times. The needle was removed and the vial was heated at 75° C. for 3 h. The reaction mixture was cooled to room temperature and treated with saturated aqueous NaCl solution (5 mL) and extracted with ethyl acetate (3*10 mL). The extracts were combined, dried (Na2SO4), filtered and concentrated. The crude product was dissolved in a small amount of DCM and purified on silica gel column chromatography eluting with a 10 min gradient from 5%-100% DCM/EtOAc. No separation was observed. A mixture of tert-butyl 4-(2-(3,4-dimethoxyphenyl)-3-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate (Intermediate 5B) and the regioisomer tert-butyl 4-(3-(3,4-dimethoxyphenyl)-2-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)-5,6-dihydropyridine-1 (2H)-carboxylate was isolated (100 mg, 77% yield), m/z (550, M+1) and was used as such in subsequent step.
  • 17
  • [ 124432-70-8 ]
  • [ 286961-14-6 ]
  • [ 2337333-70-5 ]
YieldReaction ConditionsOperation in experiment
30% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In 1,4-dioxane; ethanol; water at 150℃; for 0.166667h; Inert atmosphere; Microwave irradiation; 1 Step 1. tert-Butyl 4-(5-fluoro-6-methoxypyridin-3-yl)-1,2,3,6-tetrahydropyridine-1- carboxylate. tert-Butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine- 1(2H)-carboxylate (1.02 g, 3.30 mmol) and 5-bromo-3-fluoro-2-methoxypyridine (0.62 g, 3.00 mmol) were combined and dissolved in dioxane (7 mL) and ethanol (3 mL) and nitrogen gas was bubbled through the mixture. Water (2 mL), aqueous potassium carbonate (2.0 M, 4.5 mL, 9.00 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.17 g, 0.15 mmol) were added and the mixture was heated at 150oC for 10 min by microwave. The mixture was poured into ethyl acetate (30 mL), the aqueous layer was removed and the organic layer was washed with brine (20 mL), dried (MgSO4) and concentrated under vacuum. The residue was purified by flash chromatography (elution with 5-30% ethyl acetate in heptane) to afford the title compound (0.28 g, 30%) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.96 (d, J = 2.0 Hz, 1H), 7.38 (dd, J = 2.0, 11.4 Hz, 1H), 6.00 (br s, 1H), 4.10 (d, J = 2.8 Hz, 2H), 4.05 (s, 3H), 3.66 (t, J = 5.7 Hz, 2H), 2.49 (br s, 2H), 1.51 (s, 10H). [M+H] = 309.0.
  • 18
  • [ 1226808-77-0 ]
  • [ 286961-14-6 ]
  • [ 2396751-66-7 ]
YieldReaction ConditionsOperation in experiment
50% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate In 1,4-dioxane at 90℃; for 14h; Inert atmosphere; 52.1 step 1: tert-butyl 4-(4-bromo-5-(2,4-difluorophenoxy)-2-nitrophenyl)-3,6-dihydropyridine-1(2H)- carboxylate At room temperature,1-bromo-2-(2,4-difluorophenoxy)-4-iodo-5-nitrobenzene (0.20 g, 0.44 mmol),Tert-Butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate Acid ester (0.16 g, 0.53 mmol),Potassium phosphate (0.19 g, 0.88 mol) and [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (0.032 g, 0.044 mmol)Dissolved in anhydrous dioxane (10 mL),The nitrogen was replaced three times, heated to 90 ° C, and reacted for 14 hours.After completion of the reaction, the reaction solution was diluted with ethyl acetate (30 mL), filtered through celite, celite washed with ethyl acetate (20 mL), the organic phase was washed with saturated brine (10mL * 3) ,, dried over anhydrous sodium Dry, filter, spin dry, and the crude product was separated by column chromatography ( petroleum ether: ethyl acetate = 3:1) to give tert-butyl 4-(4-bromo-5-(2,4-difluorophenoxy) 2-nitrophenyl)-3,6-dihydropyridine-1(2H)-carboxylate (0.17 g, pale yellow solid, yield: 50%).
  • 19
  • [ 1186663-45-5 ]
  • [ 286961-14-6 ]
  • [ 2316842-45-0 ]
YieldReaction ConditionsOperation in experiment
54.3% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate In 1,4-dioxane; water at 90℃; for 16h; 2.1 1) Methyl 3-(1-(tert-butoxycarbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1-methyl-1H-indole-6-carboxylate preparation Dissolve methyl 3-bromo-1-methyl-1H-indole-6-carboxylate (2.0g, 7.46mmol) in a mixed solvent of 1,4-dioxane (50mL) and water (10mL) Add 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridine-1-(2H)-carboxy Tert-butyl ester (3.46g, 11.2mmol), [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (546mg, 0.75mmol) and sodium carbonate (1.6g, 15.1mmol) It was reacted at 90°C for 16 hours, concentrated, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 3:1) to obtain the product (1.5 g, yield 54.3%).
  • 20
  • [ 1245647-95-3 ]
  • [ 286961-14-6 ]
  • [ 2639522-42-0 ]
YieldReaction ConditionsOperation in experiment
69.8% Stage #1: tert-butyl N-(2-bromothiazol-4-yl)carbamate; tert-Butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-1(2H)-pyridinecarboxylate With potassium phosphate In 1,4-dioxane; water for 0.166667h; Inert atmosphere; Stage #2: With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 In 1,4-dioxane; water at 110℃; for 12.0833h; Inert atmosphere; 410 Intermediate 410D: Tert-butyl 4-(4-((tert-butoxycarbonyl) amino) thiazol-2-yl)-3, 6- dihydropyridine- 1 (2H)-carboxylate To a stirred solution of tert-butyl (2-bromothiazol-4-yl)carbamate (7.2 g, 25.8 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridine- 1(2H)-carboxylate (11.96 g, 38.7 mmol) in dioxane (150 mL) and water (16.67 mL) was added potassium phosphate tribasic (16.42 g, 77 mmol). The resulting solution was degassed with nitrogen for 10 mins. Next, PdCl2(dppf)-CH2Cl2 adduct (2.106 g, 2.58 mmol) was added and the reaction mixture was degassed again for 5 min. The resulting brown colored reaction mixture was heated to 110 °C for 12 h. The reaction was diluted with EtO Ac (250 mL), washed with water (250 mL) and aqueous layer was extracted with ethyl acetate (2 X 200) mL. The combined organic layer was dried over sodium sulphate, filtered and concentrated to get crude product. The crude product was purified by Combiflash using 80 g silica column by eluting with 45% EtO Ac/Pet. ether. Following concentration of fractions, tert-butyl 4-(4-((tert-butoxy carbonyl) amino) thiazol-2-yl)-3, 6-dihydropyridine-1(2H)-carboxylate (7.8 g, 17.99 mmol, 69.8 % yield) was collected as a yellow oil. LCMS retention time 3.31 min [C]. MS (E-) m/z: 382.2 (M+H).
  • 21
  • [ 174913-13-4 ]
  • [ 286961-14-6 ]
  • [ 2640048-97-9 ]
YieldReaction ConditionsOperation in experiment
81% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate In 1,4-dioxane; water at 80℃; for 3h; Inert atmosphere; 39.a Step a: To a mixture of Intermediate 1 (0.30 g, 1.17 mmol) and tert-butyl 4-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (0.44g, 1.41 mmol) and Na2CO3 (0.38 g, 3.54 mmol) in water (1 mL) and 1,4-dioxane (5 mL) was added Pd(dppf)Cl2^CH2Cl2(20 mg, 0.02 mmol) at room temperatureunder nitrogenatmosphere. The mixture was stirred 80oC for 3 hunder nitrogenatmosphere. After cooling to room temperature, the reaction mixture was poured into water (50 mL) and extracted with EA (3 x 50 mL). The combined organic layers were washed with brine (2 x 50 mL) and 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/EA (8/1) to afford to afford tert-butyl 4-(2,3-dichloro-6-methoxyphenyl)-1,2,3,6-tetrahydropyridine-1-carboxylate as a light solid (0.38 g, 81%): LCMS (ESI) calc’d for C17H21Cl2NO3 [M + H - 15]+: 343, 345 (3 : 2), found 343, 345 (3 : 2)
  • 22
  • [ 130191-91-2 ]
  • [ 286961-14-6 ]
  • [ 2756312-86-2 ]
YieldReaction ConditionsOperation in experiment
67.67% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II) dichloromethane adduct; anhydrous sodium carbonate In tetrahydrofuran; methanol; lithium hydroxide monohydrate at 100℃; for 12.3333h; Inert atmosphere; 41.1 Step 1: To a stirred solution of 4-bromo-3,5-difluoro-phenol (2.5 g, 11.96 mmol) in THF (20 mL) Methanol (5 mL) and Water (5 mL) was added tert-butyl 4-(4,4,5,5-tetramethyl-l,3,2- dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-l-carboxylate (5.55 g, 17.94 mmol) and degassed with N2 for 20 minutes. Pd(dppf)C12 .Dichloromethane (0.98 g, 1.20 mmol), Sodium carbonate (3.80 g, 35.89 mmol, 1.50 mL) were added to the reaction mixture and heated at 100 °C for 12 h. The reaction mixture was filtered and concentrated under reduced pressure to get crude which was purified by column chromatography on silica gel eluted with 20 % ethyl acetate in petroleum ether to yield tert-butyl 4-(2,6-difluoro-4-hydroxy-phenyl)-3,6-dihydro-2H-pyridine-l-carboxylate (3.0 g, 8.09 mmol, 67.67% yield) as an off white solid. LCMS (ESI-): 310.1 [M-H]-.
67.67% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II) dichloromethane adduct; anhydrous sodium carbonate In tetrahydrofuran; methanol; lithium hydroxide monohydrate at 100℃; for 12.3333h; Inert atmosphere; 41.1 Step 1: To a stirred solution of 4-bromo-3,5-difluoro-phenol (2.5 g, 11.96 mmol) in THF (20 mL) Methanol (5 mL) and Water (5 mL) was added tert-butyl 4-(4,4,5,5-tetramethyl-l,3,2- dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-l-carboxylate (5.55 g, 17.94 mmol) and degassed with N2 for 20 minutes. Pd(dppf)C12 .Dichloromethane (0.98 g, 1.20 mmol), Sodium carbonate (3.80 g, 35.89 mmol, 1.50 mL) were added to the reaction mixture and heated at 100 °C for 12 h. The reaction mixture was filtered and concentrated under reduced pressure to get crude which was purified by column chromatography on silica gel eluted with 20 % ethyl acetate in petroleum ether to yield tert-butyl 4-(2,6-difluoro-4-hydroxy-phenyl)-3,6-dihydro-2H-pyridine-l-carboxylate (3.0 g, 8.09 mmol, 67.67% yield) as an off white solid. LCMS (ESI-): 310.1 [M-H]-.
  • 23
  • [ 1126824-74-5 ]
  • [ 286961-14-6 ]
  • [ 2768360-67-2 ]
YieldReaction ConditionsOperation in experiment
69% Stage #1: 8-bromo-[1,2,4]triazolo[4,3-a]pyridine; 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester With tetrakis-(triphenylphosphine)-palladium; potassium carbonate In 1,4-dioxane; lithium hydroxide monohydrate Reflux; Stage #2: With trifluoroacetic acid In dichloromethane at 20℃; for 1h; 4.1; 8.1 Step 1: 8-(l,2,3,6-Tetrahydropyridin-4-yl)-[l,2,4]triazolo[4,3-a]pyi'idine (21-1). To a solution of 8-bromo-[l,2,4]triazolo[4,3-a]pyridine (0.500 g, 2.52 mmol) in dioxane:water (10: 1, 11 mL) was added tert-butyl 4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-3,6-dihydropyridine-l(2H)-carboxylate (1.17 g, 3.79 mmol), K2CO3 (0.698 g, 5.05 mmol) and Pd(PPh3)4 (0.146 g, 0.126 mmol) and the mixture was heated to reflux overnight. To this was then added brine (50 mL) then extracted with EtOAc (50 mL x 3). The organic layer was dried with Na2SO4, filtered, then concentrated and purified via silica gel chromatography eluting 0-100% EtOAc in hexanes followed by 0-20% MeOH in CH2Q2. The product was isolated as a pink solid. The product was then concentrated and dissolved in CH2Q2 (10 mL) and then added TFA (3 mL) and stirred at room temperature for ~1 h. To the reaction mixture was added sat. NaHCOs (aq) (50 mL) then extracted with CH2Q2 (50 mL x 3). The organic layers were isolated and concentrated to yield 21-1 as a yellow solid. Yield = 0.352 g (69%). M/Z: 201 [M+H]+.
69% Stage #1: 8-bromo-[1,2,4]triazolo[4,3-a]pyridine; 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester With tetrakis-(triphenylphosphine)-palladium; potassium carbonate In 1,4-dioxane; lithium hydroxide monohydrate Reflux; Stage #2: With trifluoroacetic acid In dichloromethane at 20℃; for 1h; 4.1; 8.1 Step 1: 8-(l,2,3,6-Tetrahydropyridin-4-yl)-[l,2,4]triazolo[4,3-a]pyi'idine (21-1). To a solution of 8-bromo-[l,2,4]triazolo[4,3-a]pyridine (0.500 g, 2.52 mmol) in dioxane:water (10: 1, 11 mL) was added tert-butyl 4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-3,6-dihydropyridine-l(2H)-carboxylate (1.17 g, 3.79 mmol), K2CO3 (0.698 g, 5.05 mmol) and Pd(PPh3)4 (0.146 g, 0.126 mmol) and the mixture was heated to reflux overnight. To this was then added brine (50 mL) then extracted with EtOAc (50 mL x 3). The organic layer was dried with Na2SO4, filtered, then concentrated and purified via silica gel chromatography eluting 0-100% EtOAc in hexanes followed by 0-20% MeOH in CH2Q2. The product was isolated as a pink solid. The product was then concentrated and dissolved in CH2Q2 (10 mL) and then added TFA (3 mL) and stirred at room temperature for ~1 h. To the reaction mixture was added sat. NaHCOs (aq) (50 mL) then extracted with CH2Q2 (50 mL x 3). The organic layers were isolated and concentrated to yield 21-1 as a yellow solid. Yield = 0.352 g (69%). M/Z: 201 [M+H]+.
  • 24
  • [ 1211526-51-0 ]
  • [ 286961-14-6 ]
  • [ 2851875-17-5 ]
YieldReaction ConditionsOperation in experiment
70.11 % With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate In 1,4-dioxane; water at 80℃; 76 Synthesis of 76a Into a 20mL sealed tube were added 5-feromo-2-methyl-3-(trifiuQromethy)pyridine (1 .00 g, 4.166 mmol, LOO equiv), dioxane (8.00 mi,), H2O (2,00 ml,), tert-butyl 4-(4, 4,5,5- tetramethyl~1 ,3,2~dioxaborolan~2~yi)~3,6-dihydro~2H~pyridine~1 -carboxylate (1.29 g, 4.172 mmol, 1.00 equiv), Pd(dppf)Cl2(0.30 g, 0.4G7 mmol, 0.10 equiv), and K3Rq4(1.77 g, 8.333 mmol, 2.00 equiv) at room temperature. The resulting mixture was stirred for 6I1 at 80 degrees C under nitrogen atmosphere. The reaction was concentrated under reduced pressure. The residue was purified by Prep-TLC (PE/EtOAc 3:1) to afford 76a (1 g, 70.11%) as a white solid.
70.11 % With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate In 1,4-dioxane; water at 80℃; 76 Synthesis of 76a Into a 20mL sealed tube were added 5-feromo-2-methyl-3-(trifiuQromethy)pyridine (1 .00 g, 4.166 mmol, LOO equiv), dioxane (8.00 mi,), H2O (2,00 ml,), tert-butyl 4-(4, 4,5,5- tetramethyl~1 ,3,2~dioxaborolan~2~yi)~3,6-dihydro~2H~pyridine~1 -carboxylate (1.29 g, 4.172 mmol, 1.00 equiv), Pd(dppf)Cl2(0.30 g, 0.4G7 mmol, 0.10 equiv), and K3Rq4(1.77 g, 8.333 mmol, 2.00 equiv) at room temperature. The resulting mixture was stirred for 6I1 at 80 degrees C under nitrogen atmosphere. The reaction was concentrated under reduced pressure. The residue was purified by Prep-TLC (PE/EtOAc 3:1) to afford 76a (1 g, 70.11%) as a white solid.
  • 25
  • [ 1211526-51-0 ]
  • [ 286961-14-6 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
95.81 % With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate In 1,4-dioxane; water at 80℃; Inert atmosphere; 178 Synthesis of 175 To a sthed solution of 1 O7a (150 mg, 0.308 mmo1 LOO equiv) and (3S)-3- fluoropyrrolidine hydrochloride (115.93 mg, 0,924 mmol, 3 equiv) in T)CE (5 mL) were added TEA (93.42 mg, 0S24 mrnol, 3 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for Iii at room temperature. To the above mixture was added STAB (130.44 mg. 06i6 mmoi, 2 equiv) at room temperature. The resulting mixture was stirred for additional 3h at room temperature. The reaction was quenched by the addition of NH4.C1 (aq.) (20 mL) at room temperature. The aqueous layer was extracted with DCM (2x20 niL), The crude product (100 mg) was purified by Prep HPLC with the foflowing conditions (Column: XBridge Prep 0131) Ci 8 Column, 30*150 mm, 5arn; Mobile Phase A: Water( 10 rnrnol/L NH4HCO3), Mobile Phase B: ACN; Flow rate:60 rnL/rnin; Gradient: 25% B to 45% B in 7 mint Wave Length: 220 rim; RTI(rnin): 630) to afford 109 (33.7 mg, 1924%) as a yeflow solid.LC-MS: (ES, m/z): [M+H] 561H-NMR: (400 MHz, CD3OD, Sppm): 1.99-2.11 (m, 1H), 2.18-2.25 (m, 1H), 2.47-2.51 (m, 1H), 2.69-2.8 1 (m, 1H), 2.89-2.98 (m, 2H), 3.01 (s, 3H), 3.51 (s, 2H), 3.66 (s, 2H), 3.78 (s, 3H), 5.06 (s, 4H), 5.12-5.26 (m, 1H), 6.38 (s, 1H), 6.85-6.86 (m, 1H), 7.11-7.13 (m, 2H),7.25-7.26 (m, 1H), 7.70(s, 1H), 8.23 (s, 1H).
95.81 % With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate In 1,4-dioxane; water at 80℃; Inert atmosphere; 178 Synthesis of 175 To a sthed solution of 1 O7a (150 mg, 0.308 mmo1 LOO equiv) and (3S)-3- fluoropyrrolidine hydrochloride (115.93 mg, 0,924 mmol, 3 equiv) in T)CE (5 mL) were added TEA (93.42 mg, 0S24 mrnol, 3 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for Iii at room temperature. To the above mixture was added STAB (130.44 mg. 06i6 mmoi, 2 equiv) at room temperature. The resulting mixture was stirred for additional 3h at room temperature. The reaction was quenched by the addition of NH4.C1 (aq.) (20 mL) at room temperature. The aqueous layer was extracted with DCM (2x20 niL), The crude product (100 mg) was purified by Prep HPLC with the foflowing conditions (Column: XBridge Prep 0131) Ci 8 Column, 30*150 mm, 5arn; Mobile Phase A: Water( 10 rnrnol/L NH4HCO3), Mobile Phase B: ACN; Flow rate:60 rnL/rnin; Gradient: 25% B to 45% B in 7 mint Wave Length: 220 rim; RTI(rnin): 630) to afford 109 (33.7 mg, 1924%) as a yeflow solid.LC-MS: (ES, m/z): [M+H] 561H-NMR: (400 MHz, CD3OD, Sppm): 1.99-2.11 (m, 1H), 2.18-2.25 (m, 1H), 2.47-2.51 (m, 1H), 2.69-2.8 1 (m, 1H), 2.89-2.98 (m, 2H), 3.01 (s, 3H), 3.51 (s, 2H), 3.66 (s, 2H), 3.78 (s, 3H), 5.06 (s, 4H), 5.12-5.26 (m, 1H), 6.38 (s, 1H), 6.85-6.86 (m, 1H), 7.11-7.13 (m, 2H),7.25-7.26 (m, 1H), 7.70(s, 1H), 8.23 (s, 1H).
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Chemical Structure| 885693-20-9

[ 885693-20-9 ]

tert-Butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate

Similarity: 0.91

Chemical Structure| 286961-15-7

[ 286961-15-7 ]

Benzyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate

Similarity: 0.89

Chemical Structure| 1227068-67-8

[ 1227068-67-8 ]

1-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridin-1(2H)-yl)ethanone

Similarity: 0.81

Chemical Structure| 844501-00-4

[ 844501-00-4 ]

(1-(tert-Butoxycarbonyl)-1,2,3,6-tetrahydropyridin-4-yl)boronic acid

Similarity: 0.81

Chemical Structure| 1121057-77-9

[ 1121057-77-9 ]

tert-Butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydropyridine-1(2H)-carboxylate

Similarity: 0.79