Home Cart 0 Sign in  

[ CAS No. 762262-09-9 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
Chemical Structure| 762262-09-9
Chemical Structure| 762262-09-9
Structure of 762262-09-9 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 762262-09-9 ]

Related Doc. of [ 762262-09-9 ]

Alternatived Products of [ 762262-09-9 ]

Product Details of [ 762262-09-9 ]

CAS No. :762262-09-9 MDL No. :MFCD07368877
Formula : C6H8BNO3 Boiling Point : -
Linear Structure Formula :- InChI Key :DHQMUJSACXTPEA-UHFFFAOYSA-N
M.W : 152.94 Pubchem ID :23546919
Synonyms :

Calculated chemistry of [ 762262-09-9 ]

Physicochemical Properties

Num. heavy atoms : 11
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.17
Num. rotatable bonds : 2
Num. H-bond acceptors : 4.0
Num. H-bond donors : 2.0
Molar Refractivity : 40.55
TPSA : 62.58 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -7.19 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.0
Log Po/w (XLOGP3) : 0.06
Log Po/w (WLOGP) : -1.23
Log Po/w (MLOGP) : -1.19
Log Po/w (SILICOS-IT) : -1.22
Consensus Log Po/w : -0.72

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -1.1
Solubility : 12.2 mg/ml ; 0.0799 mol/l
Class : Very soluble
Log S (Ali) : -0.93
Solubility : 18.1 mg/ml ; 0.118 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -1.03
Solubility : 14.4 mg/ml ; 0.094 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.99

Safety of [ 762262-09-9 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H332-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 762262-09-9 ]

* 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 [ 762262-09-9 ]

[ 762262-09-9 ] Synthesis Path-Downstream   1~85

  • 1
  • [ 762262-09-9 ]
  • [ 1030626-89-1 ]
  • C17H20N6 [ No CAS ]
  • [ 1030627-16-7 ]
YieldReaction ConditionsOperation in experiment
With sodium t-butanolate;tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 110℃; for 7.01667h; Example 4: 4-{8-[4-(4-Methyl-piperazin-l-yl)-phenylamino]-[l,2,4]triazolo[l,5-a]pyridin-5-yl}- lH-pyridin-2-one4.1 [5-(2-Methoxy-pyridin-4-yl)-[l,2,4]triazolo[l,5-a]pyridin-8-yl]-[4-(4-methyl-piperazin-l-yl)- phenyl] -amine[0401] A suspension of 5-chloro-[l,2,4]triazolo[l,5-a]pyridin-8-yl)-[4-(4-methyl-piperazin-l- yl) -phenyl] -amine (50 mg, 146 mumol), 2-methoxypyridin-4-boronic acid (45 mg, 290 mumol), Pd(PPh3)4 (51 mg, 40 mumol) and NaO'Bu (56 mg, 580 mumol) in 1.2 mL of DMF/water (5: 1, degassed) is degassed for 1 min in a sealed tube. The tube is sealed and the reaction mixture heated at 110 0C for seven hours. The reaction is complete after 3 hours (HPLC). No change of composition of the reaction mixture is detected after seven hours. After evaporation of the solvents, the residue is purified by flash chromatography (silica gel, dichloromethane/7N NH3 in methanol 100:0 to 96:4) affording the title compound (44 mg), which is isolated as a mixture containing 39 percent of product and 50percent of de- chlorinated starting material (HPLC).
  • 2
  • [ 762262-09-9 ]
  • [ 1030626-90-4 ]
  • [ 1030627-17-8 ]
YieldReaction ConditionsOperation in experiment
With sodium t-butanolate;tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 110℃; for 5.01667h; 5.1 4-[5-(2-Methoxy-pyridin-4-yl)-[l,2, 4] triazolo [1, 5 -a] pyridin-8-ylamino] -N-pyridin- 3 -ylmethy I- benzamide <n="105"/>[0403] A suspension of 4-(5-chloro-[l,2,4]triazolo[l,5-a]pyridin-8-ylamino)-N-pyridin-3- ylmethyl-benzamide (50 mg, 132 mumol), 2-methoxypyridin-4-boronic acid (40 mg, 260 mumol), Pd(PPh3)4 (46 mg, 40 mumol) and NaO'Bu (51 mg, 530 mumol) in 1.2 mL of DMF/water (5:1, degassed) is degassed for 1 min in a sealed tube. The tube is sealed and the reaction mixture heated at 110 0C for five hours. After evaporation of the solvents, the residue is purified by flash chromatography (silica gel, dichloromethane/7N NH3 in methanol 97:3) affording the title compound (46 mg), which is isolated as a mixture containing 50 percent of product.
  • 3
  • [ 762262-09-9 ]
  • [ 1030626-94-8 ]
  • [ 1030626-53-9 ]
YieldReaction ConditionsOperation in experiment
69.8% With potassium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; water; at 105 - 110℃; for 20h; D.3 N-(4-(4-Ethylpiperazin-l-yl)phenyl)-5-(2-methoxypyridin-4-yl)-[l,2,4]triazolo[l,5-a]pyridin-8- amine <n="80"/>[0352] To a reaction vial (40 mL), is added 5-chloro-N-(4-(4-ethylpiperazin-l-yl)phenyl)-[l,2,4]triazolo[l,5-alpha]pyridin-8-amme (110 mg, 0.3 mmol), potassium carbonate (207 mg, 1.5 mmol, 5 eq.), <strong>[762262-09-9]2-methoxypyridin-4-ylboronic acid</strong> (70 mg, 0.45 mmol, 1.5 eq), PddppfCl2 (44 mg, 20percent), dioxane (4.0 mL) and water (1.0 mL). The reaction mixture is degassed and filled with argon. The reaction is heated at 105-1100C for 2Oh. After cooling to rt, ethyl acetate (10 mL) is added to each reaction vial. The organic phase is filtered through a pat of celite and then is evaporated to give a residue that is purified by silica gel column chromatography (1-3percent 2N NH3 in MeOH/DCM) to give the title compound as a light yellow solid (90 mg, yield, 69.8percent). 1H NMR (300 MHz, OMSO-d6): delta 8.75 (s, IH), 8.56 (s, IH), 8.26 (d, J = 6.0 Hz, IH), 7.60 (d, J = 4.8 Hz), 7.58 (s, IH), 7.46 (d, J= 8.4 Hz, IH), 7.25 (d, J = 9.0 Hz, 2H), 6.96 (d, J= 9.0 Hz, 2H), 6.93 (d, J= 8.4 Hz, IH), 3.91 (s, 3H), 3.12 (m, 4H), 2.50 (m, 4H), 2.36 (q, J= 6.9, 2H), 1.04 (t, J= 6.9 Hz, 3H); LCMS-ESI (m/z): calcd for C24H27N7O, 429; [M+H]+ found, 430.
  • 4
  • [ 762262-09-9 ]
  • [ 1040538-72-4 ]
  • [ 1040540-16-6 ]
YieldReaction ConditionsOperation in experiment
43.1% To a 20 mL microwave tube was added N- [2-[(4-bromophenyl)methyl]-5-hydroxy-6-(l- methylethyl)-3-oxo-2,3-dihydro-4-pyridazinyl]carbonyl}glycine (example 61, 31 mg, 0.073 mmol), [2-(methyloxy)-4-pyridinyl]boronic acid (11.18 mg, 0.073 mmol), potassium carbonate (30.3 mg, 0.219 mmol), and tetrakis(triphenylphosphine)palladium (0) (2.53 mg, 2.192 mumol) in 1,4-Dioxane (1.5 ml) and Water (0.500 ml). The mixture was irradiated at 100 0C for 20 minutes. The reaction mixture was diluted with water (4 ml) and acidified with IN HCl (1 ml) then filtered to remove any residue followed by purification by HPLC chromatography (ODS silica, gradient 10-75percent acetonitrile/water (0.1percent TFA)) to afford the title compound N- [5-hydroxy-6-(l - methylethyl)-2-({4-[2-(methyloxy)-4-pyridinyl]phenyl}methyl)-3-oxo-2,3-dihydro-4- pyridazinyl]carbonyl} glycine (15 mg, 0.031 mmol, 43.1 percent yield). IH NMR (400 MHz, DMSO- d6) d ppm 15.89 (s, 1 H), 12.96 (br. s., 1 H), 10.18 (t, J=5.56 Hz, 1 H), 8.22 (d, J=5.31 Hz, 1 H), 7.76 (d, J=8.34 Hz, 2 H), 7.42 (d, J=8.34 Hz, 2 H), 7.30 (dd, J=5.43, 1.39 Hz, 1 H), 7.10 (s, 1 H), 5.31 (s, 2 H), 4.10 (d, J=5.81 Hz, 2 H), 3.89 (s, 3 H), 3.19 (sept, J=6.78 Hz, 1 H), 1.21 (d, J=6.82 Hz, 6 H). MS(ES+) m/e 453 [M+H]+.
  • 5
  • [ 762262-09-9 ]
  • [ 1004294-68-1 ]
  • N-(2'-methoxy-3-methyl-2,4'-bipyridin-6-yl)-1-(4-methoxyphenyl)-cyclopropanecarboxamide trifluoroacetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 80℃; for 36h; AQ. l-(4-Methoxyphenyl)-N-(5-methyl-6-(2-oxo-l,2-dihydropyridin-4- yl)pyridin-2-yl)cvclopropanecarboxamide; Step a: N-(2 '-Methoxy-3-methyl-2, 4 '-bipyridin-6-yl)-l-(4-methoxyphenyl)- cyclopropanecarboxamide; N-(6-Chloro-5-methylpyridin-2-yl)-l-(4-methoxyphenyl)cyclopropane carboxamide (63 mg, 0.20 mmol) was dissolved in 1,2-dimethoxyethane (2.0 mL) in a reaction <n="116"/>tube. 2-Methoxypyridin-4-ylboronic acid (46 mg, 0.30 mmol), aqueous 2 M sodium carbonate (0.20 mL), and (PlIsP)4Pd (12 mg, 0.010 mmol) were added and the reaction mixture was heated at 80 0C under N2 atmosphere for 18 hours. Since the reaction was incomplete, it was re-treated with same amount of boronic acid, base and Pd catalyst and heated at 80 0C for 18 hours. The resulting material was cooled to room temperature, filtered, and evaporated under reduced pressure. The crude product was dissolved in DMSO (2 mL), filtered, and purified by reverse phase preparative HPLC to yield N-(2'-methoxy-3-methyl-2,4'-bipyridin-6-yl)-l-(4- methoxyphenyl)cyclopropane carboxamide. ESI-MS m/z calc. 389.2, found 390.5 (M+l)+. Retention time 1.84 minutes.
  • 6
  • [ 762262-09-9 ]
  • N-(6-chloro-5-methylpyridin-2-yl)-1-(2,3-dihydrobenzofuran-5-yl)cyclopropanecarboxamide [ No CAS ]
  • [ 1083168-31-3 ]
YieldReaction ConditionsOperation in experiment
34% With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 120℃; for 0.333333h;microwave irradiation; CC. l-(2.3-Dihvdrobenzofuran-5-yl)-N-(5-methyl-6-(2-oxo-1.2-dihvdropyridin-4-yl)pyridin-2-yl)cvclopropanecarboxamide; Step a: l-(2,3-Dihydrobenzofuran-5-yl)-N-(2'-methoxy-3-methyl-2,4'-bipyridin-6-yl)cyclopropanecarboxamide; To N-(6-chloro-5-methylpyridin-2-yl)-l-(2,3-dihydrobenzofuran-5- yl)cyclopropanecarboxamide (95 mg, 0.3 mmol) in 1,2-dimethoxy ethane (3 mL) was added 2- methoxypyridin-4-ylboronic acid (66 mg, 0.4 mmol), tetrakis(triphenylphosphine)palladium (O) (33 mg, 0.03 mmol), and 2 M sodium carbonate (0.45 mL, 0.9 mmol). The reaction mixture was irradiated in the microwave at 120 0C for twenty minutes. The reaction mixture was diluted with ethyl acetate (5mL) and washed with water (5mL). The organics were dried over sodium sulfate and evaporated to dryness. The crude reaction mixture was purified by silica gel chromatography eluting with (0-50percent ethyl acetate/hexanes) to yield the product (42 mg, 34percent). ESI-MS m/z calc. 401.17, found 402.5 (M+l)+. Retention time 1.88 minutes.
  • 7
  • [ 762262-09-9 ]
  • [ 1083168-78-8 ]
  • [ 1083168-61-9 ]
YieldReaction ConditionsOperation in experiment
44% With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 80℃; CT. l-f2.2-difluorobenzordiri.31dioxol-5-vn-N-(2'-methoxy-3.4-dimethyl-2.4'- bipyridin--vDcyclopropanecarboxamide; A solution of N-(6-chloro-4,5-dimethylpyridin-2-yl)-l-(2,2- difluorobenzo[d][l,3]dioxol-5-yl)cyclopropanecarboxamide (38 mg, 0.1 mmol) in DME (1 mL) was added to a reaction tube containing <strong>[762262-09-9]2-methoxypyridin-4-ylboronic acid</strong> (46 mg, 0.15 mmol) and Pd(PPh3)4 (6 mg, 0.005 mmol). Saturated Na2CO3 solution was added (100 muL) and the reaction was stirred at 80 0C overnight. The reaction was filtered, concentrated and purified by column chromatography (0-50percent ethyl acetate in hexanes) to obtain 40 mg (44percent) of a clear oil. ESI-MS m/z calc. 453.4, found 454.3 (M+l)+. Retention times: 2.06 minutes. H NMR (400 MHz, DMSO) 8.85 (s, IH), 8.20 (d, J = 5.2 Hz, IH), 7.86 (s, IH), 7.54 (d, J = 1.5 Hz, IH), 7.39 (d, J = 8.3 Hz, IH), 7.32 (dd, J = 1.6, 8.3 Hz, IH), 6.97 (dd, J = 1.2, 5.2 Hz, IH), 6.77 (s, IH), 3.87 (s, 3H), 2.31 (s, 3H), 2.09 (s, 3H), 1.51 - 1.48 (m, 2H), 1.17 - 1.15 (m, 2H).
  • 8
  • [ 762262-09-9 ]
  • [ 1083168-79-9 ]
  • [ 1083167-95-6 ]
YieldReaction ConditionsOperation in experiment
88% With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 80℃; for 56h; BF. 1 -(2.3-Dihvdrobenzofuran-5-yl)-N-(2'-methoxy-3.4-dimethyl-2.4'-bipyridin-6-yl)cyclopropanecarboxamide; To N-(6-chloro-4,5-dimethylpyridin-2-yl)-l-(2,3-dihydrobenzofuran-5- yl)cyclopropanecarboxamide (100 mg, 0.29 mmol), <strong>[762262-09-9]2-methoxypyridin-4-ylboronic acid</strong> (67 mg, 0.44 mmol) and tetrakis(triphenylphosphine)palladium (O) (34 mg, 0.029 mmol) in 1,2- dimethoxy ethane (3.0 mL), 2 M nua2C03 (438 muL, 0.87 mmol) was added. The reaction mixture was stirred and heated at 80 0C for 16 hours under N2 atmosphere. Product and starting material were observed. 0.5 Equivalents of <strong>[762262-09-9]2-methoxypyridin-4-ylboronic acid</strong> and 0.05 equivalents of tetrakis(triphenylphosphine)palladium (0) were added and continued heating for 40 hours. The reaction mixture was diluted with ethyl acetate (5 mL), dried over Na2SO4, filtered and evaporated under reduced pressure. The crude product was purified by column chromatography on silica gel (0-30percent ethyl acetate in hexane) to yield l-(2,3-dihydrobenzofuran-5-yl)-N-(2'- methoxy-S^-dimethyl^^'-bipyridin--y^cyclopropanecarboxamide as a yellow solid (107 mg, 88percent). ESI-MS m/z calc. 415.5, found 416.7 (M+l)+. Retention time 1.74 minutes.
  • 9
  • [ 762262-09-9 ]
  • [ 1083168-81-3 ]
  • [ 1083168-12-0 ]
YieldReaction ConditionsOperation in experiment
42% With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 120℃; for 0.333333h;microwave irradiation; BU. l-(2.3-Dihvdrobenzofuran-5-yl)-N-(4-methyl-6-(2-oxo-1.2-dihvdropyridin-4-yl)pyridin-2-yl)cvclopropanecarboxamide; Step a: l-(2,3-Dihydrobenzofuran-5-yl)-N-(2'-methoxy-4-methyl-2,4'-bipyridin-6-yl)cyclopropanecarboxamide; To N-(6-chloro-4-methylpyridin-2-yl)-l-(2,3-dihydrobenzofuran-5- yl)cyclopropanecarboxamide (150 mg, 0.46 mmol) in 1,2-dimethoxy ethane (4 mL) was added <strong>[762262-09-9]2-methoxypyridin-4-ylboronic acid</strong> (84 mg, O. 55 mmol), tetrakis(triphenylphosphine)palladium (O) (53 mg, 0.046 mmol), and 2 M nua2C03 (680 muL, 1.4 mmol). The reaction mixture was irradiated in the microwave at 120 0C for 20 minutes. The reaction mixture was evaporated to dryness and the residue was purified by silica gel chromatography eluting with (0-20percent ethyl acetate/hexanes) to yield l-(2,3-dihydrobenzofuran-5-yl)-N-(2'-methoxy-4-methyl-2,4'- bipyridin-6-yl)cyclopropanecarboxamide (76 mg, 42percent). ESI-MS m/z calc. 401.2, found 402.3 (M+l)+. Retention time 1.88 minutes.
  • 10
  • [ 762262-09-9 ]
  • [ 1065074-14-7 ]
  • [ 1146614-59-6 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,4-dioxane; water; at 100℃; for 2h; To a solution of 3-bromo-6-bromo-imidazo[1,2-a]pyridine (Intermediate H) (1 eq, 0.72 mmol, 0.2 g), 3-methoxypyrid-4-yl boronic acid (1.0 eq, 0.72 mmol, 0.11 g), Na2COs (2 eq, 1.44 mmol, 152 mg) in dioxane (45 ml) and water (13.5 ml) under inert atmosphere of argon is added bis(triphenylphosphine)palladium II chloride (0.1 eq, 0.07 mmol, 50 mg). The reaction mixture is heated at 100 °C for 2 hours. The mixture is diluted with H2O (50 ml) and extracted with EtOAc. The combined organic portions are washed with brine, dried (MgSpsi4) and concentrated in vacuo. The residue is purified by flash chromatography on silica eluting with 25-75percent ethyl acetate in iso- hexane to afford the title compound; [M+H]+ = 333
  • 11
  • [ 762262-09-9 ]
  • [ 1186334-51-9 ]
  • [ 1186332-15-9 ]
YieldReaction ConditionsOperation in experiment
50% With potassium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,2-dimethoxyethane; water; at 80℃; for 3h; Step 7: 7-(8-ethyl-8-azabicyclo[3.2.1]octan-3-yl)-3-iodo-2-(pyridin-4- yl)pyrazolo[1 ,5-a]pyrimidine (150 mg, 0.32 mmol) and <strong>[762262-09-9]2-methoxypyridin-4-ylboronic acid</strong> (100 mg, 0.65 mmol) were dissolved in ethylene glycol dimethyl ether (3 ml.) and to the resulting solution was added (1 ,1 '-bis(diphenylphosphino)ferrocene) dichloropalladium(ll) dichloromethane complex (53 mg). A solution of potassium carbonate (90 mg, 2.24 mmol) in water (0.5 ml.) was next added to the reaction mixture, and the reaction was heated to 80° C for 3 hours. The reaction was then cooled and saturated sodium bicarbonate (20 ml.) was added. The mixture was then extracted with dichloromethane (2 x 50 ml_). The organic layer was dried over anhydrous sodium sulfate, filtered, and the filtrate was evaporated to yield a solid. The crude solid was purified by silica gel flash chromatography, eluting with 15percent methanol in dichloromethane, to give 0.07 g (50percent yield) of 7-(8-ethyl-8- azabicyclo[3.2.1]octan-3-yl)-3-(2-methoxypyridin-4-yl)-2-(pyridin-4-yl)pyrazolo[1 ,5- a]pyrimidine. MS: 441.3 [M+H].
  • 12
  • [ 762262-09-9 ]
  • [ 1198759-24-8 ]
  • [ 1198759-42-0 ]
  • 13
  • [ 762262-09-9 ]
  • [ 1231926-43-4 ]
  • [ 1231922-22-7 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate;trans-bis(triphenylphosphine)palladium dichloride; In 1,2-dimethoxyethane; water; at 100℃; for 0.5h;Microwave irradiation; STEP 2: N-(4-(2'-METHOXY-3,4'-BIPYRIDIN-2-YLOXY)PHENYL)-5-METHYLPYRIDIN-2-AMINE To a glass microwave vial was added N-(4-(3-bromopyridin-2-yloxy)phenyl)-5-methylpyridin-2-amine (0.2017 g, 0.566 mmol), <strong>[762262-09-9]2-methoxypyridin-4-ylboronic acid</strong>, trans-dichlorobis(triphenylphosphine) palladium (II) (0.032 g, 0.045 mmol), and sodium carbonate (0.300 g, 2.83 mmol) in DME (0.906 mL) and water (0.226 mL). The reaction mixture was stirred and heated in a Biotage Initiator microwave reactor at 100° C. for 30 min. The crude product was purified by chromatography to give the title compound. MS (ESI, pos. ion) m/z: 356 (M+1). IC50 (uM) 0.003548.
  • 14
  • [ 762262-09-9 ]
  • [ 1095708-39-6 ]
  • [ 1095708-40-9 ]
YieldReaction ConditionsOperation in experiment
With caesium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In tetrahydrofuran; water; for 4h;Reflux; Inert atmosphere; Step 9.2. 6-Chloro-2-(4-fluorophenyl)-3-(2-methoxypyrid-4-yl)imidazo[1,2-b]pyridazine (According to Scheme 6) To a suspension of 5.7 g (14.8 mmol) of 6-chloro-2-(4-fluorophenyl)-3-iodoimidazo[1,2-b]pyridazine in 370 mL of a mixture of tetrahydrofuran and water (9:1) are added 14.7 g (44.4 mmol) of cesium carbonate and 2.77 g (17.8 mmol) of (2-methoxypyrid-4-yl)boronic acid. After sparging with a stream of argon for a few moments, 0.98 g (1.2 mmol) of a complex of [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) and dichloromethane (PdCl2(dppf).CH2Cl2) is added and the reaction mixture is refluxed under argon for 4 hours. The medium is then concentrated under reduced pressure to give a black residue. The residue is taken up in 200 mL of water, the product is extracted with 500 mL of dichloromethane, the organic phase is dried by passing through a hydrophobic filter, filtered and the solvent is evaporated off to give 7 g of residue. The product is purified by chromatography on silica gel, eluding with a mixture of dichloromethane and ethyl acetate (100:0 to 70:30) to give 3.5 g of beige-colored crystals after crystallization from diisopropyl ether and drying under reduced pressure. m.p.: 184° C. 1H NMR (DMSO-d6) delta: 8.30 (m, 2H), 7.60 (m, 2H), 7.45 (d, 1H), 7.20 (pseudo t, 2H), 7.05 (m, 2H), 2.90 (s, 3H) ppm.
  • 15
  • [ 762262-09-9 ]
  • [ 1236119-31-5 ]
  • [ 1236118-38-9 ]
YieldReaction ConditionsOperation in experiment
With sodium hydrogencarbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; at 135℃; for 0.5h;Inert atmosphere; microwave irradiation; sealed vial; (S)-3-((4-(4-bromophenyl)piperazin-1-yl)methyl)-7,8,9,10-tetrahydro-5H-dipyrido[1,2-a:3',2'-e]pyrazin-6(6aH)-one (0.04 mmol), <strong>[762262-09-9]2-methoxypyridin-4-ylboronic acid</strong> (0.060 mmol), PdCl2(dppf)-CH2Cl2 Adduct (3.27 mg, 4.00 mumol), sodium bicarbonate (0.500 ml, 0.500 mmol), dioxane (Volume: 1 ml) and a stir bar were sealed in a 5 mL microwave vial. The vial was heated to 135° C. for 30 minutes. The aqueous layer was removed from the vial and reaction mixture the filtered into a 1.8 mL HPLC submission vial. The reaction mixture was purified by LCMS to give a yellow solid: [M+H] calc'd for C28H32N6O2, 485; found, 485.
  • 16
  • [ 762262-09-9 ]
  • [ 1227089-74-8 ]
  • [ 1227090-00-7 ]
YieldReaction ConditionsOperation in experiment
With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In acetonitrile; at 120℃; for 0.0833333h;Inert atmosphere; Microwave irradiation; Example 28 6-(2-methoxypyridin-4-yl)-l-methyl-4-(4-(methylsulfonyl)phenoxy)- 1 H-pyrazolo[3 ,4-b]pyridine 118[00248] 4,6-Dichloro-l-methyl-lH-pyrazolo[3,4-6]pyridine 5 (0.5 g, 4.9 mmol) was dissolved in acetonitrile (8 mL) and <strong>[762262-09-9]2-methoxypyridine-4-boronic acid</strong> (0.4 g) and 1 M KOAc (8 mL) were added in a microwave tube. Nitrogen was bubbled through the solution for 5 minutes. l,l '-Bis(diphenylphosphino)ferrocenepalladium (II) chloride (1.21 g) was added and the resultant mixture was then heated by microwave at 120 0C for 5 minutes. The reaction mixture was concentrated in vacuo and purified by flash chromatography (30percent EtOAc in hexane) to provide 4-chloro-6-(2-methoxypyridin-4-yl)-l -methyl- lEta-pyrazo Io [3,4- b]pyridine (0.37 g). [00249] To 4-chloro-6-(2-methoxypyridin-4-yl)- 1 -methyl- 1 H-pyrazolo [3 ,4-b]pyridine(0.4 g) and 4-(methylsulfonyl)phenol (0.5 g) was added DMF (3.4 niL) and potassium carbonate (1.0 g). Nitrogen was bubbled through the solution for 5 min. The reaction mixture was heated in a microwave reactor for 1 h at 150 0C, then purified by reverse phaseHPLC to provide 118 (0.3 g). MS (ESI) m/z 411.1 (M+l)+
  • 17
  • [ 762262-09-9 ]
  • [ 958006-20-7 ]
  • [ 1227071-33-1 ]
  • 18
  • [ 762262-09-9 ]
  • [ 1338050-97-7 ]
  • [ 1338051-01-6 ]
YieldReaction ConditionsOperation in experiment
73% With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 100℃; for 1h; 6A: 4-Amino-7-(2-methoxypyridin-4-yl)pyrro^acid[00143] A suspension of 2C (400 mg, 1.56 mmol), <strong>[762262-09-9]2-methoxypyridin-4-ylboronic acid</strong> (428 mg, 2.80 mmol) and aq. potassium carbonate (2.33 mL, 4.67 mmol) in DMF (10 mL) was degassed then treated with teirato(triphenylphosphine)palladium (0) (90 mg, 0.078 mmol). The mixture was heated at 100 °C for lh then cooled and diluted with water. The solution was brought to ~pH6 with glacial HO Ac, and the resulting precipitate was filtered, rinsed with ether, and air-dried. The mother liquor was partially concentrated, and a second crop was collected, rinsed with ether and air- dried. Combination of the two crops afforded 6A (324 mg, 73percent yield) as a cream- colored solid. MS (ES): m/z= 286.3 [M+H]+. 1H NMR (400 MHz, DMSO-d6) delta ppm 13.43 (br. s, IH); 9.65 (br. s, IH); 8.46 (br. s, I H); 8.22 (d, IH, J = 5.27 Hz); 8.15 (s, IH); 7.73 (s, IH); 7.65 - 7.71 (m, 2H); 3.90(s, 3H).
  • 19
  • [ 762262-09-9 ]
  • [ 1337567-12-0 ]
  • [ 1337567-13-1 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In 1,4-dioxane; water; at 100℃; for 0.0833333h;microwave irradiation; Step F; To a solution of the intermediate from step E (70 mg, 0.108 mmol) in 1,4-dioxane (4 mL) was added 3-methoxy-5-pyridine boronic acid (66 mg. 0.54 mmol), 1,1 Bis(Di-/ert- butylphosphino)palladium dichloride (3.5 mg, 0.005 mmol) and potassium carbonate solution (1.08 mL, 1M). The resulting mixture was degassed and heated in the microwave reactor at 100°C for 5 minutes. The reaction mixture was filtered and purified by reverse phase HPLC (Gilson) using a gradient of 65-100percent acetonitrile: water to give the desired compound. LC-MS: m/z-676.4 (M+l); rt=1 4 min (Method B).
  • 20
  • [ 762262-09-9 ]
  • [ 1208069-55-9 ]
  • [ 1208069-57-1 ]
YieldReaction ConditionsOperation in experiment
With caesium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In tetrahydrofuran; water; for 16h;Reflux; Inert atmosphere; Step 4.1. 6-Chloro-2-methyl-3-(2-methoxypyridin-4-yl)imidazo[1,2-b]pyridazine A mixture of 1.15 g (3.92 mmol) of 6-chloro-3-iodo-2-methylimidazo[1,2-b]pyridazine, 0.72 g (4.7 mmol) of <strong>[762262-09-9]2-methoxypyridin-4-ylboronic acid</strong> and 3.8 g (12 mmol) of caesium carbonate in 75 ml of a mixture of tetrahydrofuran and water (90/10) is purged with argon and then 0.29 g (0.35 mmol) of a complex of 1,1'-bis(diphenylphosphino)ferrocenedichloropalladium(II) and dichloromethane (PdCl2(dppf).CH2Cl2) is added. After 16 hours of heating at reflux, the mixture is poured into 1N aqueous hydrochloric acid solution which is ice-cold, and the aqueous phase is washed with ethyl acetate and then basified by addition of sodium bicarbonate. The product is subsequently extracted with dichloromethane. The organic phase is dried over sodium sulphate and the solvent is evaporated under reduced pressure. The solid residue is purified on 35 g of silica gel, eluting with a mixture of dichloromethane, methanol and aqueous ammonia (98/2/0.2), to give 0.77 g of a white solid.m.p.: 132-134° C.1H NMR (CDCl3) delta: 8.35 (d, 1H), 7.90 (d, 1H), 7.3 (d, 1H), 7.25 (s, 1H), 7.15 (d, 1H), 4.05 (s, 3H), 2.65 (s, 3H) ppm.
  • 21
  • [ 762262-09-9 ]
  • [ 1354288-45-1 ]
  • 22
  • [ 762262-09-9 ]
  • 5,7-difluoro-N-(2'-methoxy-6-morpholino-3,4'-bipyridin-4-yl)-3-methyl-2-(pyridin-2-yl)quinolin-4-amine [ No CAS ]
  • 23
  • [ 762262-09-9 ]
  • 5,7-difluoro-N-(2'-methoxy-6-morpholino-3,4'-bipyridin-4-yl)-3-methyl-2-(4-methylpyridin-2-yl)quinolin-4-amine [ No CAS ]
  • 24
  • [ 762262-09-9 ]
  • [ 1400581-41-0 ]
  • [ 1400579-81-8 ]
YieldReaction ConditionsOperation in experiment
17% With potassium phosphate;palladium diacetate; XPhos; In 1,4-dioxane; at 100℃;Inert atmosphere; Sealed vial; Step 2: (+/ -)-4-( 1 -( 1 -cyanocyclopropanecarbonyl)-4,4-dimethylpyrrolidin-3 -ylamino)-6- (2-methoxypyridin-4-yl)pyrrolo[l,2-b]pyridazine-3-carboxamide (Example 296)[00421] A solution of (S)-6-bromo-4-(l-(l-cyanocyclopropanecarbonyl)-4,4- dimethylpyrrolidin-3-ylamino)pyrrolo[l,2-b]pyridazine-3-carboxamide (10 mg, 0.022 mmol) in 1,4-Dioxane (0.5 mL), was added <strong>[762262-09-9](2-methoxypyridin-4-yl)boronic acid</strong> (4.12 mg, 0.027 mmol), palladium (II) acetate (0.25 mg, 1.123 muiotaetaomicron), X-Phos (1.07 mg, 2.25muiotaetaomicron1) and potassium phosphate ( 2M, 0.04 mL, 0.08 mmol). The reaction vial was purged with nitrogen, sealed and heated at 100 °C overnight. The crude material was purified via preparative LC/MS with the following conditions: Column: Waters XBridge C18, 19 x 250 mm, 5-muiotaeta particles; Guard Column: Waters XBridge C18, 19 x 10 mm, 5- muiotaeta particles; Mobile Phase A: 5:95 acetonitrile:water with 10-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with 10-mM ammonium acetate; Gradient: 25- 100percent B over 25 minutes, then a 5-minute hold at 100percent B; Flow: 20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation to give the title compound (2.2 mg, 17percent yield). 3/4 NMR (500MHz, METHANOL-d4) delta 8.43 (dd, J=5.4, 2.5 Hz, 1H), 8.23 - 8.09 (m, 1H), 7.99 - 7.93 (m, 1H), 7.90 (dd, J=10.4, 1.5 Hz, 1H), 7.61 (s, 2H), 7.17 - 7.08 (m, 1H), 6.86 (d, J=8.4 Hz, 1H), 4.12 (dd, J=12.9, 6.4 Hz, 1H), 3.96 (s, 3H), 3.95 - 3.87 (m, 1H), 3.64 - 3.55 (m, 1H), 3.50 - 3.44 (m, 1H), 3.01 (s, 1H), 2.88 (s, 1H), 1.75 - 1.53 (m, 4H), 1.35 - 1.24 (m, 6H). MS (ES+) m/z: 474.2 (M+H); LC retention time: 1.41 min (analytical HPLC Method I).
  • 25
  • [ 762262-09-9 ]
  • [ 1402884-01-8 ]
  • [ 1402883-55-9 ]
  • 26
  • [ 762262-09-9 ]
  • [ 1311269-31-4 ]
  • [ 1402149-74-9 ]
  • 27
  • [ 762262-09-9 ]
  • [ 1417185-08-0 ]
YieldReaction ConditionsOperation in experiment
In 1,4-dioxane; Example 3284-(2-Methoxy-pyridin-4-yl)-6-(2-quinolin-2-yl-ethyl)-6,7-dihydro-pyrrolo[3,4-b]pyridin-5-oneThe title compound was prepared in analogy to the process described in Example 322 but using <strong>[762262-09-9]2-methoxypyridin-4-ylboronic acid</strong> (15.3 mg, 0.1 mmol) dissolved in dioxane (0.35 mL) instead of 3-methylpyridin-4-ylboronic acid (13.7 mg, 0.1 mmol) dissolved in dioxane (0.35 mL). Yield: 4.5 mg, 13percent. 1H NMR (500 MHz, DMSO/D2O) delta ppm 8.78 (d, J=5.19 Hz, 1H) 8.29 (d, J=8.24 Hz, 1H) 8.18-8.21 (m, 1H) 7.94 (d, J=7.93 Hz, 1H) 7.83 (d, J=8.54 Hz, 1H) 7.67-7.75 (m, 1H) 7.54-7.58 (m, 1H) 7.47-7.52 (m, 2H) 7.06 (dd, J=5.19, 1.53 Hz, 1H) 6.94 (s, 1H) 4.61 (s, 2H) 4.01 (t, J=7.32 Hz, 2H) 3.88 (s, 3H) 3.31 (t, J=7.02 Hz, 2H); MS (ESI) m/z 397 (M+H)+.
  • 28
  • [ 762262-09-9 ]
  • [ 1417185-24-0 ]
YieldReaction ConditionsOperation in experiment
In 1,4-dioxane; Example 3444-(2-Methoxy-pyridin-4-yl)-2-(2-quinolin-2-yl-ethyl)-2,3-dihydro-isoindol-1-oneThe title compound was prepared in analogy to the process described in Example 341 but using <strong>[762262-09-9]2-methoxypyridin-4-ylboronic acid</strong> (15.2 mg, 0.1 mmol) dissolved in dioxane (0.35 mL) instead of 2-(dimethylamino)pyrimidin-5-ylboronic acid (16.7 mg, 0.1 mmol) dissolved in dioxane (0.35 mL). Yield: 8.8 mg, 26percent. 1H NMR (500 MHz, DMSO/D2O) delta ppm 8.24-8.31 (m, 2H) 7.91 (dd, J=18.31, 7.93 Hz, 2H) 7.70-7.77 (m, 3H) 7.61-7.66 (m, 1H) 7.56 (t, J=7.02 Hz, 1H) 7.51 (d, J=8.54 Hz, 1H) 7.19 (dd, J=5.49, 1.53 Hz, 1H) 7.01 (s, 1H) 4.72 (s, 2H) 4.03 (t, J=7.17 Hz, 2H) 3.92 (s, 3H) 3.31 (t, J=7.32 Hz, 2H); MS (ESI) m/z 396 (M+H)+.
  • 29
  • [ 762262-09-9 ]
  • [ 1417190-22-7 ]
  • [ 1417182-75-2 ]
YieldReaction ConditionsOperation in experiment
40% With caesium carbonate; In 1,4-dioxane; methanol; dichloromethane; dimethyl sulfoxide; Example 2517-(2-Methoxy-pyridin-4-yl)-2-(2-quinolin-2-yl-ethyl)-2,3-dihydro-isoindol-1-oneA Personal Chemistry Ermy's optimizer microwave was used.Each microwave tube was charged with 0.1 eq. of [1,1'-Bis(diphenylphosphino)-ferrocene]dichloro-palladium(II), complex with dichloromethane (7 mg).To the microwave tube, a solution of 7-bromo-2-(2-(quinolin-2-yl)ethyl)isoindolin-1-one from Example 5.4 (30 mg, 0.08 mmol) dissolved in dioxane (1.0 mL) was added, followed by <strong>[762262-09-9]2-methoxypyridin-4-ylboronic acid</strong> (15.2 mg, 0.1 mmol) dissolved in dioxane (0.3 mL).Then, 250 muL of 1M aqueous solution of Cs2CO3 was added and the resulting mixture was heated in the microwave for 1200 sec at 120° C.The reaction was filtered, checked by LC/MS and concentrated to dryness.The residues were dissolved in 1:1 DMSO/MeOH.Purification by reverse phase HPLC gave 7-(2-methoxypyridin-4-yl)-2-(2-(quinolin-2-yl)ethyl)isoindolin-1-one (13 mg, 40percent).1H NMR (400 MHz, DMSO/D2O) delta ppm 8.28 (d, J=8.54 Hz, 1H) 8.11 (d, J=5.19 Hz, 1H) 7.91 (dd, J=23.96, 8.39 Hz, 2H) 7.63-7.75 (m, 3H) 7.53-7.59 (m, 1H) 7.48 (d, J=8.24 Hz, 1H) 7.38 (dd, J=6.10, 2.44 Hz, 1H) 6.96 (dd, J=5.34, 1.37 Hz, 1H) 6.80 (s, 1H) 4.54 (s, 2H) 3.97 (t, J=7.17 Hz, 2H) 3.87 (s, 3H) 3.28 (t, J=7.17 Hz, 2H); MS (ESI) m/z 396 (M+H)+.
  • 30
  • [ 762262-09-9 ]
  • [ 56338-00-2 ]
  • [ 1314264-22-6 ]
YieldReaction ConditionsOperation in experiment
12% With potassium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,2-dimethoxyethane; water; at 85℃; for 18h;Inert atmosphere; [00221] Intermediate 8 : 2-Chloro-5-(2-phenyl-4-(2-methoxypyridin-4-yl)-lH- imidazol-5-yl)benzoic acid[00222] Step 1 : 2-phenvl-4-bromo-5-(2-methoxvpvridin-4-yl)-lH-imidazole. A vial was charged with 4,5-dibromo-2-phenylimidazole (500 mg, 1.656 mmol), 2- methoxypyridine-4-boronic acid (253 mg, 1.656 mmol), PdCl2(PPh3)2 (58 mg, 0.083 mmol), and potassium carbonate (1.37 g, 9.94 mmol) under nitrogen atmosphere. Degassed DME (10 mL) and water (2.5 mL) were added. The reaction mixture was stirred at 85°C for 18h. The organic layer was isolated and adsorbed on silica gel. Purification on silica with a gradient of 0-60percent EtOAc/Hexane afforded 68 mg of the titled product as a light yellow solid (12percent yield): 1H NMR (DMSO-dtf, ppm) delta 3.93 (s, 3H), 7.32 (broad s, 1H), 7.46 (t, 1H), 7.54 (m, 3H), 8.05 (d, 2H), 8.29 (d, 1H), 13.1 (broad s, 1H); [M+H+] m/z 330, 332.
  • 31
  • [ 762262-09-9 ]
  • [ 1420628-45-0 ]
  • [ 1420623-40-0 ]
YieldReaction ConditionsOperation in experiment
46% With palladium diacetate; sodium carbonate; ruphos; In 1,4-dioxane; water; at 120℃; for 3h;Inert atmosphere; Compound IV-25a was prepared from compound 1-1 by coupling to ethyl 4-amino-2- chloropyrimidine-5-carboxylate using Method I. Compound IV-25a was then converted to compound IV-25 according to the following procedure: The mixture of compound IV-25a (300 mg, 0.65 mmol) and 2- methoxypyridin-4-yl)boronic acid (149 mg, 0.98 mmol) in l,4-dioxane:water (3: 1, 12 mL) was degassed and backfilled with argon (three cycles). To this mixture, 2-dicyclohexylphosphino-2',6'-diisopropoxybiphenyl (121 mg, 0.26 mmol), palladium(II) acetate (29 mg, 0.13 mmol), and Na2C03 (207 mg, 1.95 mmol) were added sequentially. The resulting mixture was degassed and backfilled with argon (three cycles), and then stirred at 120 °C for 3 h. The mixture was allowed to cool to RT, and then partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over Na2S04 and filtered. The filtrate was concentrated in vacuo and the residue was purified by ISCO column chromatography (silica gel cartridge, 0-10percent MeOH/DCM) to afford compound IV-25 (160 mg, 46percent yield). ESI-MS m/z: 537.2 [M+H]+.
  • 32
  • [ 762262-09-9 ]
  • [ 1425042-54-1 ]
  • 33
  • [ 762262-09-9 ]
  • [ 1425042-55-2 ]
  • 34
  • [ 762262-09-9 ]
  • [ 1425044-70-7 ]
  • [ 1425044-71-8 ]
YieldReaction ConditionsOperation in experiment
With palladium diacetate; sodium carbonate; ruphos; In 1,4-dioxane; water; at 120℃; for 3h;Inert atmosphere; [0846] Compound 109 was prepared from compound 8 according to Method G. Compound 109 was then converted to compound 110 according to the following procedure: The mixture of (S)-ethyl 2-amino-4-beta1-(8-chloro-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)amino)pyrimidine-5-carboxylate (300 mg, 0.65 mmol) and 2-methoxypyridin-4-yl)boronic acid (149 mg, 0.98 mmol) in 1,4-dioxane:water (3:1, 12 mL) was degassed and backfilled with argon (three cycles). To this mixture, 2-dicyclohexylphosphino-2?,6?-diisopropoxybiphenyl (121 mg, 0.26 mmol), palladium(II) acetate (29 mg, 0.13 mmol), and Na2CO3 (207 mg, 1.95 mmol) were added sequentially. The resulting mixture was degassed and backfilled with argon (three cycles), and then stirred at 120° C. for 3 h. The mixture was allowed to cool to RT, and then partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by ISCO column chromatography (silica gel cartridge, 0-10percent MeOH/DCM) to afford the product 110, (S)-ethyl 2-amino-4-((1-(8-(2-methoxypyridin-4-yl)-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)amino)pyrimidine-5-c carboxylate.
  • 35
  • [ 762262-09-9 ]
  • [ 1312579-07-9 ]
  • C43H37ClN4O5 [ No CAS ]
  • 36
  • [ 762262-09-9 ]
  • [ 1032903-50-6 ]
  • [ 1445894-91-6 ]
  • 37
  • [ 762262-09-9 ]
  • [ 1466564-54-4 ]
  • [ 1466564-57-7 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate; In 1,4-dioxane; water; at 85℃; for 16h;Inert atmosphere; A mixture of chloride 137 (28 mg, 0.060 mmol), <strong>[762262-09-9]2-methoxypyridin-4-yl boronic acid</strong> (2.0 eq), Pd(amphos)2 (10 mol percent) and sodium carbonate (2.5 eq) in dioxane/water (4/1 v/v, 3 mL) was degassed with Ar for 10 min. The resulting mixture was heated to 85° C. and stirred for 16 hr. The resulting suspension was cooled to RT, partitioned between DCM and a saturated aqueous sodium chloride solution. The organic phase was separated, dried with sodium sulfate, pre-adsorbed on silica gel and purified on silica gel column with acetone and DCM to afford the naphthylidine compound 140. ESI-MS m/z: 543.2 [M+H]+.
  • 38
  • [ 762262-09-9 ]
  • [ 1466565-04-7 ]
  • [ 1466565-05-8 ]
YieldReaction ConditionsOperation in experiment
With bis(di-tert-?butyl(4-?dimethylaminophenyl)?phosphine)?dichloropalladium(II); sodium carbonate; In 1,4-dioxane; water; at 85℃; for 1h;Inert atmosphere; Compound 218 (0.070 mmol, 1.0 equiv), <strong>[762262-09-9](2-methoxypyridin-4-yl)boronic acid</strong> (2.0 equiv), and sodium carbonate (2.0 equiv) were suspended in 2 mL dioxane/water (v/v 4:1) and bubbled with Ar for 10 min. Pd(amphos)Cl2 (5 mol percent) was added and the reaction was heated to 85° C. for 1 h, after which there was no starting material by LC/MS analysis. The reaction was allowed to cool and transferred to a separatory funnel with excess water and ethyl acetate. The organic layer was separated, dried over sodium sulfate and concentrated under vacuum to provide crude residue, which was purified using flash silica gel chromatography (ISCO, gradient 0-20percent acetone/methylene chloride) to provide compound 219. ESI-MS m/z: 516.4 [M+H]+.
  • 39
  • [ 762262-09-9 ]
  • C26H34ClN3O*ClH [ No CAS ]
  • 1-((1R,3R,5S)-9-((1R,6S,8s)-bicyclo[4.3.1]decan-8-yl)-9-azabicyclo[3.3.1]nonan-3-yl)-3-(2-methoxypyridin-4-yl)quinoxalin-2(1H)-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
56.8% With dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II); sodium t-butanolate; In 1,4-dioxane; at 25 - 150℃;Microwave irradiation; To a suspension of the hydrochloride of Compound X45 (0.31 5mmol, 1 50mg), sodi um 2- methylpropan-2-olate (NaO-t-Bu, 1 .259mmol, 121 mg, Sigma-Aldrich), and (2-methoxypyridin-4- yl)boronic acid (Compound X46, 0.630mmol, 96mg, Sigma-Aldrich) in 1 ,4-dioxane (4.5mL) at a temperature of about 25°C was added 1 , 1 '-bis (di-t-butylphosphino)ferrocene palladium(II) dichloride (0.031 mmol, 20.52mg, Sigma-Aldrich). The resulting reaction mixture was then irradiated for 2h at 1 50°C using a Biotage Initiator focused microwave heating apparatus (Uppsala, Sweden) operating at 2.45 GHz. Thereafter, the mixture was diluted with 5percent NaHC03 in EtOAc ( l OOmL) and filtrated. The filtrate was extracted with EtOAc, washed with water, washed with brine, dried (over Na2S04), and evaporated to dryness. The resulting solid was chromatographed on a on a silica-gel column (Yamazen Corp. W003) eluted with a gradient of from 0: 100 MeOH (28percent NH40H):CHC13 to 30:70 MeOH (28percent NH40H):CHC13 to provide 91 .6mg of Compound X47, l -(( lR,3R,5S)-9-(( l R,6S,85)- bicyclo[4.3. l ]decan-8-yl)-9-azabicyclo[3.3.1 ]nonan-3-yl)-3-(2-methoxypyridin-4-yl)quinoxalin- 2( lH)-one, as an orange solid (yield 56.8percent). The identity of Compound X47 was confirmed using -NMR. Compound X47: -NMR: deltaEta (ppm, 400MHz, CDC13 with one drop each of DC1 and d4- MeOH): 1.33-2.21 (m, 1 7H), 2.46-2.66 (m, 6H), 2.80-2.99 (m, I H), 3.02-3.16 (m, 2H), 3.83-3.97 (m, IH), 4. 17-4.30 (m, 2H), 4.49 (s, 3H), 6.45-6.66 (m, 1 H), 7.52 (dd, J=7.47, 7.47Hz, IH), 7.94 (dd, J=7.80, 7.80Hz, I H), 8.02 (dd, J=7.89, 1.34Hz, I H), 8.45-8.57 (m, 3H), 8.89 (d, J=8.73Hz, I H).
  • 40
  • [ 762262-09-9 ]
  • C26H34ClN3O*ClH [ No CAS ]
  • 1-((1R,3R,5S)-9-((1R,6S,8s)-bicyclo[4.3.1]decan-8-yl)-9-azabicyclo[3.3.1]nonan-3-yl)-3-(2-oxo-1,2-dihydropyridin-4-yl)quinoxalin-2(1H)-one [ No CAS ]
  • 41
  • [ 762262-09-9 ]
  • [ 1562340-90-2 ]
  • 3-fluoro-5-(2-methoxypyridin-4-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
5.7 mg With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 130℃; for 1h;Microwave irradiation; Sealed tube; GENERAL METHOD 1-6Representative procedure for the Suzuki Coupling10 Halo-pyridazine substrate (1 equivalent), boronic acid or ester reagent (2.5 equivalents), andNa2C03 (3 equivalents) were added to a microwave vial. Pd(PPh3)4 (0.1 equivalents) was thenadded to the reaction mixture followed by addition of dioxane/water (6/1, 0.1 M). The reactionmixture was sealed and heated in a Biotage® Initiator microwave reactor 130°C for 1 h. Thereaction mixture was filtered through celite and the filter cake was washed with methanol. The15 filtrate was concentrated in vacuo and the crude product was purified via reverse phase preparativeHPLC (0.1percent trifluoroacetic acid as modifier). The appropriate fractions containing product were freebased by catch and release using SiliaBond Propylsulphonic Acid® (4 eq, methanol as eluent and a2 N ammonia solution in MeOH to release the material). The solvent was concentrated in vacuoand the resulting solid was suspended or dissolved in CH3CN/H20 (3/1 ml). 1 M aqueous HCI (320 equivalents) was added and the solvent was concentrated in vacuo to afford the desired compoundas the hydrochloride salt. Following GENERAL METHOD 1-6 for Suzuki cross-coupling, 5-bromo-3-fluoro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol (Intermediate 8-1) and <strong>[762262-09-9](2-methoxypyridin-4-yl)boronic acid</strong> were reacted and the crude product was purified via reverse25 phase preparative HPLC (10percent CH3CN to 30percent in H20). After salt formation, 3-fluoro-5-(2-methoxypyridin-4-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenolhydrochloride salt was afforded as a yellow solid (5.7 mg). LCMS Rt = 0.56 min [Method Q]; [M+H]:466.4; 1H NMR (400 MHz, MeOD) 8 8.25 (d, J= 5.5 Hz, 1 H), 8.20 (d, J= 10.0 Hz, 1 H), 7.71 (d, J=10.0 Hz, 1H), 7.30 (dd, J= 5.5, 1.5 Hz, 1H), 7.21 (dd, J= 12.0, 1.5 Hz, 1H), 7.21 (s, 1H), 7.13 (d, J=30 1.0 Hz, 1 H), 5.38-5.22 (m, 1 H), 4.01 (s, 3H), 3.14 (s, 3H), 2.03 (d, J= 8.5 Hz, 4H), 1.67 (s, 6H),1.56 (s, 6H).
  • 42
  • [ 762262-09-9 ]
  • [ 1569320-04-2 ]
  • [ 1569319-75-0 ]
YieldReaction ConditionsOperation in experiment
14 mg With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,2-dimethoxyethane; water; at 95℃; for 1h;Microwave irradiation; Inert atmosphere; Under an Ar atmosphere, a mixture of 2-(5-bromo-pyridin-3-ylamino)-2-phenyl-acetamide (60 mg, 0.197 mmol), 2-methoxypyridne-4-boronic acid (39 mg, 0.256 mmol), Tetrakis(triphenylphosphine)palladium (11 mg, 0.0098 mmol) and K2CO3 (81 mg, 0.59 mmol) in DME-H20 (5: 1, 2 mL) was exposed to microwave irradiation at 95 °C for 1 fir, then concentrated in vacuo. The residue was partitioned between ethyl acetate and brine. The aqueous layer was separated and extracted with ethyl acetate. The combined organic layers were concentrated and the residue was purified by Prep-HPLC to give 2-(2'-methoxy- [3,4']bipyridinyl-5-ylamino)-2-phenyl-acetamide (14 mg).
14 mg With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,2-dimethoxyethane; water; at 95℃; for 1h;Inert atmosphere; Microwave irradiation; Under an Ar atmosphere, a mixture of 2-(5-bromo-pyridin-3-ylamino)-2-phenyl-acetamide (60 mg, 0.197 mmol), 2-methoxypyridne-4-boronic acid (39 mg, 0.256 mmol), Tetrakis(triphenylphosphine)palladium (11 mg, 0.0098 mmol) and K2CO3 (81 mg, 0.59 mmol) in DME-H2O (5:1, 2 mL) was exposed to microwave irradiation at 95° C. for 1 hr, then concentrated in vacuo. The residue was partitioned between ethyl acetate and brine. The aqueous layer was separated and extracted with ethyl acetate. The combined organic layers were concentrated and the residue was purified by Prep-HPLC to give 2-(2'-methoxy-[3,4']bipyridinyl-5-ylamino)-2-phenyl-acetamide (14 mg).
  • 43
  • [ 762262-09-9 ]
  • [ 1574389-45-9 ]
  • [ 1574388-95-6 ]
YieldReaction ConditionsOperation in experiment
82.2% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In acetonitrile; at 90℃; for 4h;Inert atmosphere; Step 1 - Synthesis of 7-(benzenesulfonyl)-4-(3,3-dimethylpiperazin-l-yl)-6-(2-methoxy-4- pyridyl)pyrrolo[2,3-d]pyrimidine (7): A mixture of 7-(benzenesulfonyl)-4-(3,3-dimethylpiperazin-l- yl)-6-iodo-pyrrolo[2,3-d]pyrimidine (6) (746.03 mg, 1.5 mmol, 1 eq), <strong>[762262-09-9](2-methoxy-4-pyridyl)boronic acid</strong> (344.12 mg, 2.25 mmol, 1.2 eq) and [l, -bis(diphenylphosphino)ferrocene]dichloropalladium(II) (109.8 mg, 0.15 mmol, 0.1 eq) in acetonitrile (15 ml) was purged with N2(g) then added 2.4 mL of 2.5M aqueous K2CO3 (4 eq). The reaction mixture was heated at 90 °C for 4 hrs. The resulting mixture was cooled & filtered through a pad of celite. The filtrate was dried over Na2S04, collected & concentrated down. The obtained residue was purified by flash chromatography eluting with 10percent methanol in CH2C12 to provide of 7-(benzenesulfonyl)-4-(3,3-dimethylpiperazin-l-yl)-6-(2-methoxy-4-pyridyl)pyrrolo[2,3-d]pyrimid (7) 590 mg (82.2percent) as a brown semi-solid. LC-MS ESI [M+H+]+ = 479.25. The data from the lB NMR spectrum were consistent with the structure of the compound.
  • 44
  • [ 762262-09-9 ]
  • [ 1574388-96-7 ]
  • 45
  • [ 762262-09-9 ]
  • [ 1574381-52-4 ]
  • 46
  • [ 762262-09-9 ]
  • [ 1610472-55-3 ]
  • [ 1610472-56-4 ]
YieldReaction ConditionsOperation in experiment
95% With tris-(dibenzylideneacetone)dipalladium(0); potassium carbonate; tricyclohexylphosphine; In 1,4-dioxane; water; at 100℃; for 4h;Inert atmosphere; To a stirred solution of 2-(4-bromo-2-fluoro-5-hydroxymethyl-benzyl)-6-tert-butyl-8-fluoro-2H- phthalazin-l-one (55 mg, 0.13 mmol) in 20percent aqueous dioxane (11 mL) were added 2-methoxy- pyridine-4-boronic acid (available from Oakwood Products, Inc., 1741 Old Dunbar Road, West Columbia, SC 29172, USA; 23 mg, 0.153 mmol), K2C03 (35 mg, 0.25 mmol), and tricyclohexylphosphine (1 mg, 0.005 mmol). The mixture was purged with argon for 20 min and Pd2(dba)3 (5 mg, 0.005 mmol) was added. The mixture was heated at 100 °C for 4 h. The mixture was concentrated and EtOAc (30 mL) was added. The resulting mixture was washed with water (3 x 5 mL) and brine (5 mL). The organic layer was dried (Na2S04), filtered, and evaporated. The residue was purified by chromatography (silica gel, 10percent> EtOAc/hexane) to give 6-tert-butyl-8-fluoro-2-[2-fiuoro-5-hydroxymethyl-4-(2-methoxy-pyridin-4-yl)-benzyl]-2H- phthalazin-l-one (56 mg, 95percent) as a yellow gum. MS calcd. for C26H26F2N303 [(M+H)+] 466, obsd. 466.0.
  • 47
  • [ 762262-09-9 ]
  • [ 1610472-34-8 ]
  • [ 1610472-35-9 ]
YieldReaction ConditionsOperation in experiment
58% With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; ethanol; water; at 90℃; for 1h;Inert atmosphere; A mixture of 2-(4-bromo-benzyl)-6-tert-butyl-8-fluoro-2H-phthalazin- 1-one (80 mg, 0.21 mmol) and Pd(PPh3)4 (1 molpercent) in DME was purged with argon for 10 min. Aqueous Na2C03 solution (2 M; 2 eq) was added and the tube was purged again with argon. The solution was stirred at room temperature for 5 min and a solution of 2-methoxy-pyridine-4-boronic acid (available from Oakwood Products, Inc., 1741 Old Dunbar Road, West Columbia, SC 29172, USA; 39.3 mg, 0.26 mmol) in EtOH was added. The mixture was purged with argon, capped, and heated at 90 °C for 1 h. The mixture was filtered through Celite and the Celite was washed with CH2CI2. The filtrate was dried (Na2S04), filtered and evaporated. The residue was purified by chromatography (silica gel) to give 6-tert-butyl-8-fluoro-2-[4-(2-methoxy-pyridin-4-yl)-benzyl]- 2H-phthalazin-l-one (50 mg, 58percent) as a gum. MS calcd. for C25H25FN302 [(M+H)+] 418, obsd. 418.
  • 48
  • [ 762262-09-9 ]
  • [ 1610472-38-2 ]
  • [ 1610472-39-3 ]
YieldReaction ConditionsOperation in experiment
62% With potassium carbonate; bis(dibenzylideneacetone)-palladium(0); tricyclohexylphosphine; In 1,4-dioxane; water; at 96℃; for 5h;Inert atmosphere; To a stirred solution of 2-(3-bromo-2-hydroxymethyl-phenyl)-6-tert-butyl-8-fluoro-2H- phthalazin-l-one (90 mg, 0.22 mmol) in 20percent aqueous dioxane (20 mL) were added 2-methoxy- pyridine-4-boronic acid (available from Oakwood Products, Inc., 1741 Old Dunbar Road, West Columbia, SC 29172, USA; 40.8 mg, 0.27 mmol), K2C03 (61.3 mg, 0.44 mmol), and tricyclohexylphosphine (3.7 mg, 0.01 mmol). The flask was evacuated and backfilled with nitrogen three times. Pd(dba)2 (6.1 mg, 0.01 mmol) was added and the mixture was heated at 96 °C for 5 h. The mixture was cooled to room temperature and the solvents were evaporated. The residue was purified by chromatography (silica gel, 20percent EtOAc/hexane) to give 6-tert-butyl-8- fluoro-2-[2-hydroxymethyl-3-(2-methoxy-pyridin-4-yl)-phenyl]-2H-phthalazin-l-one (60 mg, 62percent) as a white solid. MS calcd. for C25H25FN3O3 [(M+H)+] 434, obsd. 434.
  • 49
  • [ 762262-09-9 ]
  • [ 1610472-40-6 ]
  • [ 1610472-41-7 ]
YieldReaction ConditionsOperation in experiment
71% A solution of 2-(4-bromo-2,6-difluoro-benzyl)-6-tert-butyl-8-fluoro-2H-phthalazin-l-one (550 mg, 1.29 mmol) in DME (1.6 mL) was purged with argon for 10 min. Pd(PPh3)4 (14 mg, 0.01 mmol) was added and the mixture was purged with argon for 10 min. Aqueous Na2C03 solution (2 M; 1.3 mL, 2.6 mmol) was added and the tube was purged with argon for 5 min. The solution was stirred at room temperature for 5 min and a solution of 2-methoxy-pyridine-4-boronic acid (available from Oakwood Products, Inc., 1741 Old Dunbar Road, West Columbia, SC 29172, USA; 245 mg, 1.61 mmol) in EtOH (1.6 mL) was added. The mixture was purged with argon for 10 min, capped, and heated at 90 °C for 1 h. The mixture was filtered through Celite and the Celite was washed with CH2C12. The filtrate was dried (Na2S04), filtered and evaporated. The residue was purified by chromatography (silica gel, 15percent> EtOAc/hexane) to give 6-tert-butyl-2- [2,6-difluoro-4-(2-methoxy-pyridin-4-yl)-benzyl]-8-fluoro-2H-phthalazin-l-one (420 mg, 71percent) as a yellow solid. MS calcd. for C25H23F3N302 [(M+H)+] 454, obsd. 454.
  • 50
  • [ 762262-09-9 ]
  • [ 1610472-42-8 ]
  • [ 1610472-43-9 ]
YieldReaction ConditionsOperation in experiment
84% With tris-(dibenzylideneacetone)dipalladium(0); potassium carbonate; tricyclohexylphosphine; In 1,4-dioxane; water; at 100℃; for 4h;Inert atmosphere; To a stirred solution of 2-(4-bromo-2-hydroxymethyl-benzyl)-6-tert-butyl-8-fluoro-2H- phthalazin-l-one (60 mg, 0.143 mmol) in 20percent aqueous dioxane (11 mL) were added 2-methoxy- pyridine-4-boronic acid (available from Oakwood Products, Inc., 1741 Old Dunbar Road, West Columbia, SC 29172, USA; 26 mg, 0.17 mmol), K2C03 (39 mg, 0.29 mmol), and tricyclohexylphosphine (2 mg, 0.006 mmol). The mixture was purged with argon for 20 min and Pd2(dba)3 (5 mg, 0.006 mmol) was added. The mixture was heated at 100 °C for 4 h. The mixture was concentrated and EtOAc (30 mL) was added. The resulting mixture was washed with water (3 x 5 mL) and brine (5 mL). The organic layer was dried (Na2S04), filtered, and evaporated. The residue was purified by chromatography (silica gel, 10percent EtOAc/hexane) to give 6-tert-butyl-8-fluoro-2-[2-hydroxymethyl-4-(2-methoxy-pyridin-4-yl)-benzyl]-2H-phthalazin-l- one (54 mg, 84percent) as a yellow gum. MS calcd. for C26H26FN3O3 [(M+H)+] 448, obsd. 447.8.
  • 51
  • [ 762262-09-9 ]
  • [ 1610472-50-8 ]
  • [ 1610472-51-9 ]
YieldReaction ConditionsOperation in experiment
33% With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; ethanol; water; at 90℃; for 1h;Inert atmosphere; Sealed tube; A solution of 2-(4-bromo-3-methoxymethoxymethyl-benzyl)-6-tert-butyl-8-fluoro-2H- phthalazin-l-one (185 mg, 0.4 mmol) in DME (1.5 mL) in a sealable tube was purged with argon for 10 min. Pd(PPh3)4 (5 mg, 0.004 mmol) was added and the mixture was purged with argon for 10 min. Aqueous Na2C03 solution (0.4 mL, 0.8 mmol) was added and the tube was purged with argon for 5 min. The solution was stirred at room temperature for 5 min and a solution of 2- methoxy-pyridine-4-boronic acid (available from Oakwood Products, Inc., 1741 Old Dunbar Road, West Columbia, SC 29172, USA; 75 mg, 0.49 mmol) in EtOH (1.5 mL) was added. The mixture was purged with argon for 5 min, capped, and heated at 90 °C for 1 h. The mixture was filtered through Celite and the Celite was washed with CH2C12. The filtrate was dried (Na2S04), filtered and evaporated. The residue was purified by chromatography (silica gel, 15percent EtOAc/hexane) to give 6-tert-butyl-8-fluoro-2-[3-methoxymethoxymethyl-4-(2-methoxy- pyridin-4-yl)-benzyl]-2H-phthalazin-l-one (65 mg, 33percent) as a yellow gum. MS calcd. for C28H3iFN304 [(M+H)+] 492, obsd. 492.2.
  • 52
  • [ 762262-09-9 ]
  • [ 1613169-00-8 ]
  • [ 1613168-08-3 ]
YieldReaction ConditionsOperation in experiment
36.2 mg With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); tricyclohexylphosphine; In 1,4-dioxane; water; at 100℃; for 16h;Inert atmosphere; [000259] A mixture of <strong>[762262-09-9]2-methoxypyridine-4-boronic acid</strong> (34 mg, 0.21 mmol), 2- (4-bromophenoxy)-N- {4- [(4-ethylpiperazin- 1 -yl)methyl]-3 -(trifluoromethyl)phenyl } -acetamide (100 mg, 0.19 mmol), PCy3 (1.3 mg, 0.0047 mmol), Pd2(dba)3 (2 mg, 0.0019 mmol) and 1.27M K3P04 (0.26 mL, 0.33 mmol) in anhydrous 1,4-dioxane (6 ml) waspurged with nitrogen gas for 15 minutes. After heating at 100 °C for 16 h, the reaction mixture was cooled to room temperature, filtered through celite and washed with methanol (100 mL). The filtrate was concentrated and the residue partitioned between water (50 ml) and ethyl acetate (50 mL). The aqueous layer was extracted with ethyl acetate (50 mL). The combined organic extracts were washed with brine (100 mL), dried(Na2SO4), concentrated and the residue purified by preparative HPLC to afford N- {4-[(4- ethylpiperazin- 1-yl)methyl] -3 -(trifiuoromethyl)phenyl } -2-[4-(2-methoxypyridin-4-yl)phenoxy]acetamide (36.2 mg). ?H NMR (DMSO-d6) oe 10.41 (s, 1H), 8.18?8.17 (d, J = 5.4Hz, 1H), 8.08?8.08 (d,J= 1.7 Hz, 1H), 7.87?7.85 (d,J= 8.2 Hz, 1H), 7.78?7.76 (d, J = 8.8, 2H), 7.69?7.67 (d, J = 8.4 Hz, 1H), 7.28?7.27 (dd, J = 5.4; 1.3 Hz, 111),7.13?7.10 (d, J= 8.8 Hz, 2H), 7.06 (s, 1H), 4.80 (s, 2H), 3.88 (s, 3H), 3.54-3.51 (m, 3H), 2.37?2.27 (m, 8H), 0.99?0.95 (t, J= 7.1 Hz, 3H); ESI MS: m/z 529 [M+H].
  • 53
  • [ 762262-09-9 ]
  • [ 1611002-10-8 ]
  • [ 1611002-11-9 ]
YieldReaction ConditionsOperation in experiment
31.4% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In N,N-dimethyl-formamide; at 120℃; for 2h;Inert atmosphere; The compound of example 238 (0.300 g, 0.804 mmol) was treated with 2- methoxypyridin-4-ylboronic acid (0.154 g, 1 .005 mmol) in the presence of [1 ,1 '- bis(diphenylphosphino)-ferrocene]dichloropalladium(ll) complex with dichloromethane (0.019 g, 0.024 mmol) and sodium carbonate (0.170 g, 1 .608 mmol) in dry dimethylformamide (10 mL) according to the procedure for the preparation of the compound of example 2 to afford the title compound. Yield: 0.102 g (31 .4 percent); 1H NMR (DMSO-de, 300 MHz): delta 3.95 (d, 6H, J =8.7 Hz, 20CH3), 7.02 (d, 1 H, J =8.4 Hz, Ar), 7.91 (s, 1 H, Ar), 8.1 1 (d, 1 H, J =2.4 Hz, Ar), 8.13 (d, 1 H, J =2.4 Hz, Ar), 8.56 (d, 1 H, J =2.1 Hz, Ar), 8.94 (s, 1 H, Ar), 9.03 (s, 2H, Ar); MS (ES+): m/e 402.3 (M+1 ).
  • 54
  • [ 762262-09-9 ]
  • [ 1620294-98-5 ]
  • [ 1620292-88-7 ]
YieldReaction ConditionsOperation in experiment
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,4-dioxane; ethanol; water; at 100℃; for 2h;Inert atmosphere; To a previously degassed solution of tert-butyl ((5-((2-bromophenoxy)methyl)-4,5-dihydroisoxazol-3-yl)methyl)carbamate (1.250 g, 3.244 mmol) in 1 ,4-dioxane: water:ethanol (1.0: 0.25: 0.082) (35 mL) was added (2-methoxypyridin-4-yl) boronic acid(0.741 g, 4.867 mmol), followed by potassium carbonate (1.342 g, 9.734 mmol) and1,1? -Bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex(0.26 1 g, 0.324 mmol) at room temperature under nitrogen atmosphere. The resultingreaction mixture was stirred for 2 h at 100 °C. The reaction mixture was filtered throughcelite pad and it was washed with ethyl acetate (2 x 40 mL). Aqueous, ethyl acetate layerwas separated. The combined ethyl acetate layer was washed with water, brine solution (2 x 20 mL). The organic phase was dried over sodium sulfate and concentrated underreduced pressure to give a residue. The residue was purified by combiflash columnchromatography (ethyl acetate/hexanes = 45/55) to give the titled compound (0.602 g, 44percent) as a liquid. LCMS: m/z 414.4 [M+ H] 1H NMR (400 MHz, Chloroform-d) 8.18(dt, J= 5.4, 0.9 Hz, 1H), 7.41 ?7.32 (m, 2H), 7.11 ?7.04 (m, 2H), 6.97 (dd, J= 8.3, 1.0Hz, 1H), 6.91 (dt, J= 1.5, 0.9 Hz, 1H), 4.92 (tt, J= 7.3, 3.7 Hz, 1H), 4.75 (s, 1H), 4.04(dd, J= 10.2, 3.5 Hz, 1H), 3.99 (d, J= 1.0 Hz, 3H), 3.94 (d, J= 6.1 Hz, 2H), 3.05 (ddd, J= 17.3, 11.2, 1.1 Hz, 1H), 2.91 (dd, J= 17.3, 7.3 Hz, 1H), 1.44 (d, J= 0.9 Hz, 9H).
  • 55
  • [ 762262-09-9 ]
  • [ 1618663-35-6 ]
  • [ 1618663-48-1 ]
YieldReaction ConditionsOperation in experiment
71% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate tribasic trihydrate; In 1,4-dioxane; water; at 80℃; for 1.5h; To a degassed mixture of 2-chloro-5-iodo-4-((tetrahydro-2H-pyran-4-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine (1 equiv), <strong>[762262-09-9](2-methoxypyridin-4-yl)boronic acid</strong> (2 equiv) and tripotassium phosphate trihydrate (3 equiv) in a 9:1 mixture of 1,4-dioxane and water (0.1 M) was added palladium 1,1-bis(diphenylphosphion)ferrocene dichloride (0.2 equiv). The reaction mixture was stirred at 80° C. for 1.5 h. After the reaction was complete, the reaction mixture was cooled to room temperature and concentrated. The residue was purified by silica gel chromatography (15percent ethyl acetate in petroleum ether) to afford the title compound (71percent yield) as a white powder. MS (ESI) m/z 491.3 [M+1]+.
  • 56
  • [ 762262-09-9 ]
  • [ 1595284-69-7 ]
  • [ 1622053-03-5 ]
YieldReaction ConditionsOperation in experiment
52% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In N,N-dimethyl-formamide; at 100℃; for 1h;Inert atmosphere; To a N2 degassed solution of 5-bromo-2-iodo-N-methyl-6-(N-methylmethylsulfonamido) benzofuran-3-carboxamide (300 mg, 0.3 mmol), <strong>[762262-09-9](2-methoxypyridin-4-yl)boronic acid</strong> (94 mg, 0.3 mmol) and K2C03 (195 mg, 0.9 mmol) in DMF (4 mL) was added Pd(dppf)Cl2 (5 mg) under N2. The mixture was stirred at 100 °C for 1 h. After the solvent was removed, the residue was purified by prep-TLC (DCM : EtOAc = 5 : 1) to give the product of compound 2 (150 mg, yield: 52percent). 1H- MR (CDC13, 400 MHz) delta 8.29 (d, J= 5.6 Hz, 1H), 8.10 (s, 1H), 7.71 (s, 1H), 7.32-7.34 (m, 1H), 7.22 (s, 1H), 5.96 (s, 1H), 3.98 (s, 3H), 3.33 (s, 3H), 3.09 (s, 3H), 3.02 (d, J = 4.8 Hz, 3H). MS (M+H)+: 468 / 470.
  • 57
  • [ 762262-09-9 ]
  • 4-(2,6-dichloro-4-isothiocyanatophenyl)-2-methoxypyridine [ No CAS ]
  • 58
  • [ 762262-09-9 ]
  • N-((3,5-dichloro-4-(2-methoxypyridin-4-yl)phenylamino)(methylthio)methyl)cyanamide [ No CAS ]
  • 59
  • [ 762262-09-9 ]
  • N3-[3,5-dichloro-4-(2-methoxypyridin-4-yl)-phenyl]-1H-[1,2,4]triazole-3,5-diamine [ No CAS ]
  • 60
  • [ 762262-09-9 ]
  • 4-[4-(5-amino-1H-[1,2,4]triazol-3-ylamino)-2,6-dichlorophenyl]-1H-pyridin-2-one [ No CAS ]
  • 61
  • [ 762262-09-9 ]
  • [ 1350643-72-9 ]
  • [ 1425045-77-7 ]
YieldReaction ConditionsOperation in experiment
10685] An appropriately sized reaction vessel was equipped with a mechanical stirrer, gas inlet/outlet, optical oxygen sensor (for headspace oxygen), reflux condenser and temperature probe. Compound 2 (1 kg, 1 wt., 1 equiv.), <strong>[762262-09-9]2-methoxypyridine-4-boronic acid</strong> (1.1 equiv.) and potassium phosphate monohydrate (2 equiv.) were charged to the reaction vessel. 1-BuOR (8 vol) and water (4 vol) were charged to the reaction vessel. The mixture was stirred at 25±5° C. The content of the vessel was sparged with inert gas (nitrogen) for minimum of 30 mm to remove dissolved oxygen. The palladium catalyst (0.01 equiv.) was charged via a solid charge port and the mixture was continuously sparged with inert gas for minimum of 10 mm. The mixture was heated to 80±5° C. (target temperature 80-83° C.) under inert atmosphere, and stirred at this temperature under inert atmosphere for minimum of 4 hrs. After the reaction was found to be complete ( 1.0percent Compound 2 relative to Compound 3 as determined by HPLC), the reaction mixture was cooled to 20±5° C. The two layers were split. The aqueous layer (bottom) was returned to the reactor and back extracted by stirring.with 1-BuOR (2 vol.) for a minimum of 10 mm. The twolayers were split. The weight of the aqueous layer was determined and the aqueous layer was assayed by HPLC to estimate the yield loss of Compound 3. The organic layers werecombined, and telescoped into the next step. Where the nextstep was not carried out on the same day, the solution was keptat 20±5° C. under inert head space.10684] Step 1:
  • 62
  • [ 762262-09-9 ]
  • (S)-2-amino-4-((1-(8-(2-methoxypyridin-4-yl)-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)amino)pyrimidine-5-carbonitrile sulfuric acid salt [ No CAS ]
  • 63
  • [ 762262-09-9 ]
  • (S)-2-amino-4-((1-(8-(2-methoxypyridin-4-yl)-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)amino)pyrimidine-5-carbonitrile maleic acid salt [ No CAS ]
  • 64
  • [ 762262-09-9 ]
  • [ 1425042-18-7 ]
  • 65
  • [ 762262-09-9 ]
  • (7S)-3-iodo-7-methyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one [ No CAS ]
  • (7S)-3-(2-methoxy-4-pyridyl)-7-methyl-5-[4-(trifluoromethyl)phenyl]-6,7-dihydropyrazolo[1,5-a]pyrazin-4-one [ No CAS ]
  • 66
  • [ 762262-09-9 ]
  • (7S)-3-iodo-7-methyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one [ No CAS ]
  • 3-(2-methoxy-pyridin-4-yl)-7(S)-methyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
86% With tetrakis(triphenylphosphine) palladium(0); sodium hydrogencarbonate; In 1,4-dioxane; water; at 100℃; for 72h;Inert atmosphere; Intermediate 25 (1-25) 3-(2-Methoxy-pyn^in-4-yl)-75'-methyl-6,7-dihydro-5H-pyrazolo[l,5-a]pyrazin-4-one Pd(PPh3)4 (0.42 g, 0.36 mmol) was added to a stirred suspension of intermediate 1-13 (2 g, 7.22 mmol) and <strong>[762262-09-9]2-methoxypyridine-4-boronic acid</strong> (1.77 g, 11.55 mmol) in 1,4- dioxane (16 mL) and a sat. sol. of NaHC03 (8 mL) in a sealed tube under nitrogen atmosphere. The mixture was stirred at 100 °C for 3 days. Then the mixture was diluted with H20 and extracted with DCM. The organic layer was separated, dried (Na2S04), filtered and the solvent evaporated in vacuo. The crude product was purified by flash column chromatography (silica; MeOH in DCM 0/100 to 6/94). The desired fractions were collected and the solvents evaporated in vacuo to yield intermediate compound 1-25 as a pale brown solid (1.6 g, 86percent).
  • 67
  • [ 762262-09-9 ]
  • ((1S,3R)-3-((5-bromo-2,3-dihydro-1H-inden-1-yl)amino)-1-isopropylcyclopentyl)(7-(trifluoromethyl)-3,4-dihydroisoquinolin-2(1H)-yl)methanone [ No CAS ]
  • C34H38F3N3O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1-methyl-pyrrolidin-2-one; toluene; at 80℃; General procedure: To a series of 1.5 mL glass tubes was added 15 in toluene ( 0.1 mmol) followed by solutions of different aryl boronic acids (0.5 M, 0.2 mmol) in NMP and these mixtures were subsequently treated with Na2CO3 solution ( 1 M, 0.2 mmol) followed by Pd(PPh3)4 in toluene (0.05 eq, 0.005 mmol). Vials with the reaction mixture (0.15 M) were capped and heated at 80 °C on a reaction block overnight. The reaction mixtures were purified directly using an automated mass-guided reverse phase-HPLC, and product containing fractions were concentrated to give final products >90percent purity as judged by LC-MS (average of 220 nm and 254 nm traces).
  • 68
  • [ 762262-09-9 ]
  • (3S)-2-((benzyloxy)carbonyl)-8-(6-((1R)-1-(4-bromo-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)-2-methylpyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid [ No CAS ]
  • C40H40F3N7O6 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium phosphate; Pd(N,N-dimethyl-beta-alaninate)2; In ethanol; water; at 50℃; for 12h; General procedure: To a mixture of (S)-2-((benzyloxy)carbonyl)-8-(6-((R)-l-(4-bromo-2-(3-methyl- lH-pyrazol-l-yl)phenyl)-2,2,2-trifluoiOethoxy)-2-methylpyrimidin-4-yl)-2,8- diazaspiro[4.5]decane-3-carboxylic acid (product of Step 3, Example 10m) (150 mg, 0.2 mmol), an arylboronic acid (0.4 mmol), Pd(N,N-dimethyl p-alaninate)2 (3.42 mg, 0.01 mmol), and K3PO4 (128 mg, 0.6 mmol) were added water (3.0 mL) and EtOH (3.0 mL). The mixture was stirred at 50 °C for 12 h. The reaction was then cooled to RT, diluted with water, and extracted with EtOAc. The combined organic layers were dried over Na2S04, filtered, and concentrated in vacuo. The target biaryl compounds were purified by normal phase silica gel column (CH2Cl2:MeOH).
  • 69
  • [ 762262-09-9 ]
  • 1-(2,3-dihydro-1H-inden-2-yl)-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine [ No CAS ]
  • 1-(2,3-dihydro-1H-inden-2-yl)-3-(2-methoxypyridin-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In water; N,N-dimethyl-formamide; at 90℃; for 16h; To a solution of 1- (2,3-dihydro- 1 H-inden-2-yl)-3-iodo- 1 H-pyrazolo [3,4- d]pyrimidin-4-amine (150 mg, 0.397 mmol) in DMF (3 mL) was added 2-methoxypyridin-4- ylboronic acid (91.23 mg, 0.596 mmol) at RT. Then, Na2CO3 (126.4 mg, 1.19 mmol) dissolved in water (3 mL) was added to the reaction mixture followed by addition of Pd(PPh3)4 (45.95 mg, 0.039 mmol) at RT and the resultant reaction mixture was heated at 90°C for 16 h. The progress of reaction was monitored by TLC and by LCMS. After completion of reaction, the reaction mixture was diluted with water (20 mL) and the product was extracted with EtOAc (3x25 mL). The combined organic layers were washed with water (2x40 mL), brine (20 mL), dried over sodium sulfate and concentrated to get a crude product which was purified by preparative HPLC affording 1-(2,3-dihydro-1H-inden-2-yl)-3-(2- methoxypyridin-4-yl)- 1 H-pyrazolo [3 ,4-d]pyrimidin-4-amine (75 mg) as an off-white solid. The crude product (12 mg) was added to ethanolic HC1 (2 mL) and stuffed for 30 mm at RT. The reaction mixture was then concentrated under reduced pressure and lyophilized to afford 1 -(2,3-dihydro- 1H-inden-2-yl)-3-(2-methoxypyridin-4-yl)- 1H-pyrazolo[3,4-d]pyrimidin-4- amine as the HC1 salt (13 mg) off-white solid. ?HNMR (400 MHz, DMSO-d6) oe (ppm): 8.58 (s, 1H), 8.39 (d, I = 2.6 Hz, 1H), 7.91 (dd, I = 8.6, 2.6 Hz, 1H), 7.33 ? 7.24 (m, 2H), 7.21 (dt, I = 5.7, 3.7 Hz, 2H), 6.98 (d, I = 8.6 Hz, 1H), 5.79 (q, I = 7.5 Hz, 1H), 3.92 (s, 3H), 3.60 ? 3.37 (m, 4H).
  • 70
  • [ 762262-09-9 ]
  • 1-(2,3-dihydro-1H-inden-2-yl)-3-(2-methoxypyridin-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine hydrochloride [ No CAS ]
  • 71
  • [ 762262-09-9 ]
  • 4-(4-amino-1-(2,3-dihydro-1H-inden-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)pyridin-2-ol [ No CAS ]
  • 72
  • [ 762262-09-9 ]
  • 4-[4-amino-1-(2,3-dihydro-1H-inden-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]pyridin-2-ol hydrochloride [ No CAS ]
  • 73
  • [ 762262-09-9 ]
  • [ 83405-70-3 ]
  • ethyl 3-tert-butyl-1-(2-methoxypyridin-4-yl)-1H-pyrazole-5-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With pyridine; copper diacetate; In N,N-dimethyl-formamide; at 20℃;Molecular sieve; Inert atmosphere; General procedure: Ethyl, 3-tert-butyl-1H-pyrazole-5-carboxylate (1 equiv.), the desired boronic acid (2 equiv.), copper (II) acetate (1.5 equiv) and dry DMF were added under stirring to give a blue solution. Dry pyridine (2 equiv.) was added, upon which the colour turned to green,followed by a spoonful of oven-dried, powdered 4 A (0.4 nm) molecular sieves. The mixture was stirred at room temperature under an argon atmosphere until reaction completion, as verified by LC-MS. After reaction completion, the mixture was diluted with AcOEt and NH4Cl solution. The organic phase was isolated, washed with NH4Cl solution, sat. aq. NaHCO3, dried (MgSO4 with Cu-catch resin), filtered, and evaporated to give an oily substance, whichin some cases was further purified by column chromatography. Method A was used with ethyl, 3-ferf-butylpyrazole-5-carboxylate (202 mg, 1.03 mmol), and <strong>[762262-09-9]2-methoxypyridin-4-yl boronic acid</strong> (208 mg, 1.360 mmol). Purification with 2? 50percent (by volume) EtOAc in hexane gave the title compound as a colorless oil. Yield: 243 mg (59percent). 1H-NMR (DMSO-d6), delta (ppm), J (Hz): 1.22 (t, 3H, 3JHH=7.1 , CH3), 1.29 (s, 9H, tert-Bu), 3.90 (s, 3H, OCH3), 4.23 (q, 2H, 3JHH=7.1 , OCH2CH3), 6.94 (d, 1 H, 3JHH=1.7, PyrH), 7.07 (s, 1 H, ArH), 7.13 (dd, 1 H, 3JHH=5.6, 1.7, PyrH), 8.23 (d, 1 H, 3JHH=5.6, PyrH). LC-MS (2.83 min): m/z calcd. for C16H21 N3O3 [M+H]+: 304.1 ; found: 303.1.
  • 74
  • [ 762262-09-9 ]
  • (4S)-7-chloro-N-(pyrazin-2-yl)-3,4-dihydro-1,4-methanopyrido[2,3-b][1,4]diazepine-5(2H)-carboxamide [ No CAS ]
  • (9S)-5-(2-methoxypyridin-4-yl)-N-(pyrazin-2-yl)-1,6,8-triazatricyclo[7.2.1.02,7]dodeca-2(7),3,5-triene-8-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
41.8% With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); XPhos; In 1,4-dioxane; water; at 100℃; for 5h;Inert atmosphere; Tripotassium phosphate (804 mg, 3.79 mmol) was added to a stirred solution of ( 4S7-chloro-N-(pyrazin-2-yl)-3,4-dihydro-1,4-methanopyrido[2,3-b][1,4]diazepine-5(2H)-carboxamide (600 mg, 1.894 mmol), (2-methoxypyridin-4-yl) boronic acid (348 mg, 2.273 mmol) in 1,4-dioxane (12 mL), and water (2.000 mL). The reaction mixture was degassed for 15 min, Pd2(dba)3 (87 mg, 0.095 mmol), and X-phos (90 mg, 0.189 mmol) were added. The reaction mixture further degassed for 15 min, and was stirred at 100 C. for 5 hr. The reaction mixture was cooled to 28 C. and was partitioned between water (25 mL) and EtOAc (60 mL). Organic layer was separated and was dried over anhydrous Na2SO4, filtered and filtrate was evaporated to get crude (TLC eluent: 10% MeOH in EtOAc; Rf=0.2; UV active). The crude compound was purified by (100-200 mesh) silica gel eluting with 20% MeOH in ethyl acetate to afford (4S)-7-(2-methoxypyridin-4-yl)-N-(pyrazin-2-yl)-3,4-dihydro-1,4-methanopyrido[2,3-b][1,4]diazepine-5(2H)-carboxamide (310 mg, 0.793 mmol, 41.8% yield) as pale yellow solid, LCMS (m/z): 390.20 [M+H]+. 1H NMR (DMSO-d6, 400 MHz): delta 13.71 (s, 1H), 9.38 (d, J=1.5 Hz, 1H), 8.43 (dd, J=2.5, 1.5 Hz, 1H), 8.38 (s, 1H), 8.37 (d, J=2.5 Hz, 1H), 7.75 (d, J=22.0 Hz, 1H), 7.77-7.62 (m, 2H), 7.60 (s, 1H), 5.50 (dd, J=5.9, 3.0 Hz, 1H), 3.94 (s, 3H), 3.30 (s, 1H), 3.25-3.03 (m, 2H), 3.03-2.88 (m, 1H), 2.25 (dd, J=9.9, 3.9 Hz, 1H), 1.98 (dd, J=14.2, 7.2 Hz, 1H).
41.8% With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); XPhos; In 1,4-dioxane; water; at 100℃; for 5h; Tripotassium phosphate (804 mg, 3.79 mmol) was added to a stirred solution of (4S)-7- chloro-N-(pyrazin-2-yl)-3,4-dihydro-l,4-methanopyrido[2,3-^][l,4]diazepine-5(2H)- carboxamide (600 mg, 1.894 mmol), (2-methoxypyridin-4-yl) boronic acid (348 mg, 2.273 mmol) in 1,4-dioxane (12 mL), and water (2.000 mL). The reaction mixture was degassed for 15 min, Pd2(dba)3 (87 mg, 0.095 mmol), and X-phos (90 mg, 0.189 mmol) were added. The reaction mixture further degassed for 15 min, and was stirred at 100 C for 5 hr. The reaction mixture was cooled to 28 C and was partitioned between water (25 mL) and EtOAc (60 mL). Organic layer was separated and was dried over anhydrous Na2S04, filtered and filtrate was evaporated to get crude (TLC eluent: 10% MeOH in EtOAc; R = 0.2; UV active). The crude compound was purified by (100-200 mesh) silica gel eluting with 20% MeOH in ethyl acetate to afford (45)-7-(2-methoxypyridin-4-yl)-N-(pyrazin-2- yl)-3,4-dihydro-l,4-methanopyrido[2,3-^][l,4]diazepine-5(2H)-carboxamide (310 mg, 0.793 mmol, 41.8 % yield) as pale yellow solid, LCMS (m/z): 390.20 [M+H]+.1H NMR (DMSO-i ,400 MHz): delta 13.71 (s, 1H), 9.38 (d, J = 1.5 Hz, 1H), 8.43 (dd, J = 2.5, 1.5 Hz, 1H), 8.38 (s, 1H), 8.37 (d, J = 2.5 Hz, 1H), 7.75 (d, J = 22.0 Hz, 1H), 7.77 - 7.62 (m, 2H),7.60 (s, 1H), 5.50 (dd, J = 5.9, 3.0 Hz, 1H), 3.94 (s, 3H), 3.30 (s, 1H), 3.25 - 3.03 (m, 2H), 3.03 - 2.88 (m, 1H), 2.25 (dd, J = 9.9, 3.9 Hz, 1H), 1.98 (dd, J = 14.2, 7.2 Hz, 1H).
  • 75
  • [ 762262-09-9 ]
  • [ 1023620-72-5 ]
  • 7-tert-butoxycarbonylamino-4-(2-methoxy-4-pyridyl)-5,7,8,9-tetrahydrobenzocyclohepten-6-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
In 1,2-dimethoxyethane;Inert atmosphere; General procedure: General procedure (a): a mixture of bromoacetamide 2a or 10a, arylboronic acid (1.5 equiv), CsF (2.2 equiv) and Pd(PPh3)4 or PEPPSI-iPr (0.1?0.15 equiv) in dry 1,2-dimethoxyethane (DME, 3 mL) was stirred under Ar at 85 °C for 16 h. The reaction mixture was diluted with AcOEt, washed with brine and dried over MgSO4. The solvent was evaporated and the residue purified by flash chromatography (cyclohexane/AcOEt). General procedure (b): same procedure with K2CO3 (1.5 equiv) as base and in DME and H2O as reaction solvent 5/1. General procedure (c): same procedure with K2CO3 (3 equiv) as base and in DME and H2O as reaction solvent 4/1. The reaction mixture was then heated at 125 °C under microwave irradiation for 30 min. General procedure (d): same procedure with K2CO3 (4 equiv) as base, and in DME and H2O as reaction solvent 4/1. The reaction mixture was then heated at 125 °C under microwave irradiation for 30 min. 6.4.1.25 7-tert-Butoxycarbonylamino-4-(2-methoxy-4-pyridyl)-5,7,8,9-tetrahydrobenzocyclohepten-6-one (31a) Pale yellow solid. Mp 76-77 °C. IR (KBr): 3414, 3285, 2979, 2940, 1721, 1675, 1610, 1546, 1466, 1389, 1252, 1166, 1041, 791 cm-1. 1H NMR (CDCl3, 400 MHz): 8.22 (d, 1H, J = 5.3 Hz, H-6'); 7.21-7.29 (m, 2H, H-3 and H-2); 7.16 (dd, 1H, J = 7.3 and 1.8 Hz, H-1); 6.95 (d, 1H, J = 5.3 Hz, H-5'); 6.80 (s, 1H, H-3'); 5.45 (d, 1H, NH); 4.57 (ddd, 1H, H-7); 4.00 (s, 3H, OMe); 3.81 (d, 1H, Ha-5); 3.69 (d, 1H, Hb-5); 3.10 (ddd, 1H, Ha-9); 2.97 (ddd, 1H, Hb-9); 2.69 (m, 1H, Ha-8); 1.51 (m, 1H, Hb-8); 1.43 (s, 9H, tBu). J(5a,5b) = 14.7, J(NH,7) = 6.8, J(7,8a) = 4.5, J(7,8b) = 11.3, J(8a,9a) = 3.5, J(8a,9b) = 8.8, J(8b,9a) = 9.1, J(8b,9b) = 3.3, J(9a,9b) = 14.6 Hz. 13C NMR (CDCl3, 100 MHz): 204.6 (C(6)); 164.3 (C(2')); 151.3 (NCO2); 147.7 (C(9a)); 146.7 (C(6')); 141.3 (C(4)); 140.0 (C(4')); 129.7 (C(4a)); 129.4 (C(2)); 128.6 (C(1)); 127.6 (C(3)); 118.4 (C(5')); 111.7 (C(3')); 79.8 (CMe3); 61.0 (C(7)); 53.6 (OMe); 43.2 (C(5)); 34.6 (C(8)); 31.5 (C(9)); 28.3 (CMe3). HR-MS (ESI-QTof) calcd for C22H27N2O4 [M+H]+: 383.1965; found: 383.1973.
  • 76
  • [ 762262-09-9 ]
  • (R)-N-(1-(4-bromophenyl)ethyl)-2-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide [ No CAS ]
  • (R)-N-(1-(4-(2-methoxypyridin-4-yl)phenyl)ethyl)-2-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; at 90℃;Inert atmosphere; To a stirred solution of (R)-.N.-( I -.(4.-hromophenyi)ethyl).-2.-methyl-.6-.oxo- I ,6.-di[ydropyrimidine--4- carhoxamide from Step A above (0.035 g, 0.104 mmol) in dioxane (0.521 mL, 0.2M) was added (2-. methoxypyridin-.4-.yl)horonic acid (0.0238 mg, 0.156 mmoi), [1,1?-? bis(diphenyiphosphino)ferroceneidichloropaliadium(11) and followed by 2M Na2CO3 (0.104 mL,0.208 mmoi). The resulting mixture was degassed, purged with nitrogen and allowed to stir overnight at 90°C. The reaction was filtered over a pad of Celite and washed with 3:1 solution of chioroform/IPA. The filtrate was concentrated under reduced pressure and the resulting residue was purified directly by reverse phase H1LC (Xterra, C18, l9xiOOmm, gradient elution, 10.-100percent acelonitrile/water with 0.1percent TFA) to yield the title compound. MS: 365.2 (M-f-H). ?H NMR (500MHz, CD3OD) oe7.82?7.44 (m, H),5.25-.5.24 (m, 1H), 4.13 (s, 3H), 2.39 (br 5, 3H), 1.63 (d, J = 6.4 Hz, 3H).
  • 77
  • [ 762262-09-9 ]
  • [ 876343-09-8 ]
  • 7-(benzenesulfonyl)-4-chloro-6-(2-methoxy-4-pyridyl)pyrrolo[2,3-d]pyrimidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
0.712 g With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In water; acetonitrile; at 100℃; for 0.666667h; To a solution of 17 (1 g, 2.38 mmol) and 2 (0.53 g, 3.57 mmol) in acetonitrile (12.45 ml, 238.31 mmol) and 1M potassium carbonate (7.15 mL) in water was added [1,1?-bis(diphenylphosphino)ferrocence]dichloropalladium (II) (0.09 g, 0.12 mmol) and the mixture was stirred at 100° C. for 40 minutes in an oil bath. Upon completion the mixture was poured over brine and extracted with ethyl acetate (3×150 mL). The organic layers were combined, dried over sodium sulfate, filtered, and then evaporated to dryness. The resulting crude solid was mounted on silica gel and purified, eluting with 20-80percent ethyl acetate in hexanes to give 0.712 g of compound (18) in 95percent purity.
  • 78
  • [ 762262-09-9 ]
  • 7-(benzenesulfonyl)-4-[4-[5-(4-fluorophenyl)-4H-1,2,4-triazol-3-yl]-1-piperidyl]-6-iodo-pyrrolo[2,3-d]pyrimidine [ No CAS ]
  • 7-(benzenesulfonyl)-4-[4-[5-(4-fluorophenyl)-4H-1,2,4-triazol-3-yl]-1-piperidyl]-6-(2-methoxy-4-pyridyl)pyrrolo[2,3-d]pyrimidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In acetonitrile; at 100℃; for 0.666667h; In a microwave reaction vessel, 7-(benzenesulfonyl)-4-[4-[5-(4-fluorophenyl)-4H-1,2,4-triazol-3-yl]-1-piperidyl]-6-iodo-pyrrolo[2,3-d]pyrimidine 13 (0.167 g, 0.265 mmol), <strong>[762262-09-9](2-methoxy-4-pyridyl)boronic acid</strong> (0.061 g, 0.4 mmol), potassium carbonate (1.06 mL, 1M, aq), acetonitrile (1.1 mL), and 1,1?-bis(diphenylphosphino)ferrocene-palladiem (II) dichloride dichloromethane complex (0.022 g, 0.027 mmol) were combined and heated at 100° C. for 40 minutes. The reaction was diluted with EtOAc and filtered through a bed of sodium sulfate. The reaction mixture was then concentrated at reduced pressure. The crude was purified via flash chromatography on silica with 0-30percent MeOH in DCM as an eluent. The fractions were combined and concentrated down to a tan oil residue (15), which was used in the next step without further purification.
  • 79
  • [ 762262-09-9 ]
  • 7-(benzenesulfonyl)-6-(2-methoxy-4-pyridyl)-4-[4-[5-(p-tolyl)-4-(trifluoromethyl)-1H-imidazol-2-yl]-1-piperidyl]pyrrolo[2,3-d]pyrimidine [ No CAS ]
  • 80
  • [ 762262-09-9 ]
  • 6-(2-methoxy-4-pyridyl)-4-[4-[5-(p-tolyl)-4-(trifluoromethyl)-1H-imidazol-2-yl]-1-piperidyl]-7H-pyrrolo[2,3-d]pyrimidine [ No CAS ]
  • 81
  • [ 762262-09-9 ]
  • [ 77902-87-5 ]
  • 1-(2-(2-methoxypyridin-4-yl)pyrrolidin-1-yl)-2,2-dimethylpropane-1-thione [ No CAS ]
  • 82
  • [ 762262-09-9 ]
  • (S)-ethyl 3-(3-((5-chloro-6-(5,5-dimethylcyclopent-1-enyl)pyrazin-2-yl)methoxy)phenyl)-3-cyclopropylpropanoate [ No CAS ]
  • (S)-ethyl 3-cyclopropyl-3-(3-((6-(5,5-dimethylcyclopent-1-enyl)-5-(2-methoxypyridin-4-yl)pyrazin-2-yl)methoxy)phenyl)propanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 90℃; for 2h;Inert atmosphere; A. (S)-Ethyl 3-cyclopropyl-3-(3-((6-(5,5-dimethylcyclopent-1-enyl)-5-(2-methoxypyridin-4-yl)pyrazin-2-yl)methoxy)phenyl)propanoate, 29a (0368) (0369) A mixture of ethyl (3S)-3-(3-[[5-chloro-6-(5,5-dimethylcyclopent-1-en-1-yl)pyrazin-2-yl]methoxy]phenyl)-3-cyclopropylpropanoate (30f) (100 mg, 0.200 mmol), <strong>[762262-09-9](2-methoxypyridin-4-yl)boronic acid</strong> (60.0 mg, 0.390 mmol), Pd(dppf)Cl2 (8.00 mg, 0.0100 mmol) and Cs2CO3 (179 mg, 0.550 mmol) in dioxane (0.8 mL), and water (0.2 mL) was stirred for 2 h at 90° C. under N2. The reaction mixture was allowed to cool to room temperature and treated with 15 mL of water. The resulting solution was extracted with EtOAc (3×10 mL). The organic layers were combined, dried (Na2SO4) and concentrated. The residue was purified by column chromatography on silica gel (EtOAc/petroleum ether (1:100-1:10 v/v)) to give the title compound 29a. Mass Spectrum (LCMS, ESI pos.): Calcd. for C32H37N3O4: 528.3 (M+H)+; found: 528.2.
  • 83
  • [ 762262-09-9 ]
  • 2-(morpholin-4-yl)-8-[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl]-1,7-naphthyridin-4-yl trifluoromethanesulfonate [ No CAS ]
  • 4-(2-methoxypyridin-4-yl)-2-(morpholin-4-yl)-8-(1H-pyrazol-5-yl)-1,7-naphthyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
A mixture of 2-(morpholin-4-yl)-8-[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl]-1,7- naphthyridin-4-yl trifluoromethanesulfonate (320 mg, 0.21 mmol), (2-methoxypyridin-4- yl)boronic acid (94 mg, 0,62 mmol), Bis(triphenylphosphin)palladium(II)chlorid (14 mg, 0,021mmol), Caesiumcarbonate (235 mg, 0,72 mmol) in Dioxane (4 ml) were heated in a sealed tube in the Microwave at 1000 C for 30 minutes. A solution of conc. HCI (10 ml) was added and the reaction was stirred at ambient temperature for 16 hours and at 50°C for another 2 hours. The reaction mixture was filtered through a plug of Celite (1 cm). The Celite was washed with ethyl acetate (50 ml) and methanol (20 ml). The filtrate was dried over Na2SO4, the solvent wasremoved under reduced pressure. The title compound was obtained as crude product and used without further purification in the next step.
  • 84
  • [ 762262-09-9 ]
  • (2S,3R)-methyl 3-cyclopropyl-3-(2-(3-formyl-4-(tosyloxy)phenyl)chroman-7-yl)-2-methylpropanoate [ No CAS ]
  • (2S,3R)-methyl 3-cyclopropyl-3-(2-(3-formyl-4-(2-methoxypyridin-4-yl)phenyl)chroman7-yl)-2-methylpropanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium phosphate; chloro(2-dicyclohexylphosphino-2?,6?-dimethoxy-1,1?-biphenyl)(2?-amino-1,1?-biphenyl-2-yl) palladium(II); In 1,4-dioxane; water; at 80℃; for 2h;Inert atmosphere; Step 8: (2S, 3R)-methyl 3-cyclopropyl-3-(2-(3-formyl-4-(2-methoxypyridin-4-yl)phenyl) chroman7-yl)-2-methylpropanoate To a solution of (2S, 3R)-methyl 3-cyclopropyl-3-(2-(3-formyl-4- (tosyloxy)phenyl) chroman-7-yl)-2-methylpropanoate (500 mg, 0.9 11 mmol) in 1, 4-dioxane (10mL) and water (2.5 mL) were added potassium phosphate tribasic (580 mg, 2.73 mmol), 2nd Generation SPhos precatalyst (32.8 mg, 0.046 mmol) and (2-methoxypyridin -4-yl)boronic acid (279 mg, 1.82 mmol) under nitrogen. The reaction mixture was stirred at 80 °C for 2 h, then poured into water (50 mL), extracted with EtOAc (50 mL x 2). The combined organic layers were washed with brine (saturated, 50 mL), dried (Na2504), filtered and the filtrate was evaporated under reducedpressure. The resulting residue was purified by column chromatography (5i02, PE: EtOAc=30: 1 to PE: EtOAc=6:1, v/v) to give the title compound. MS (ESI) mlz: 486.3[M+H]
  • 85
  • [ 762262-09-9 ]
  • methyl (2S,3R)-3-(2-(4-chloro-2-((2,2-dimethylpyrrolidin-1-yl)methyl)phenyl)-chroman-7-yl)-3-cyclopropyl-2-methylpropanoate [ No CAS ]
  • methyl (2S,3R)-3-cyclopropyl-3-(2-(2-((2,2-dimethylpyrrolidin-1-yl)methyl)-4-(2-methoxypyridin-4-yl)phenyl)chroman-7-yl)-2-methylpropanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium phosphate; chloro(2-dicyclohexylphosphino-2?,4?,6?-triisopropyl-1,1?-biphenyl)[2-(2?-amino-1,1?-biphenyl?)]palladium(II); In tetrahydrofuran; at 80℃; for 3h;Inert atmosphere; Step 6: Methyl (2S,3R)-3-cyclopropyl-3-(2-(2-((2,2-dimethylpyrrolidin- 1 -yl)methyl)-4-(2- methoxypyridin-4-yl)phenyl)chroman-7-yl)-2-methylpropanoate To a solution of (2S ,3R)-methyl 3- (2-(4-chloro-2-((2,2-dimethylpyrrolidin- 1 -yl)methyl)phenyl)chroman-7-yl)-3 -cyclopropyl-2- methylpropanoate (120 mg, 0.242 mmol) and <strong>[762262-09-9](2-methoxypyridin-4-yl)boronic acid</strong> (74.0 mg, 0.484 mmol) in THF (3 mL) at rt was added chloro(2-dicyclohexylphosphino-2?,4?,6?-triisopropyl- 1,1?-biphenyl)[2-(2?-amino- 1,1 ?-biphenyl)]palladium(II), X-Phos aminobiphenyl palladium chloride precatalyst (2m generation Xphos precatalyst, 19.03 mg, 0.024 mmol). The reaction mixture was degassed and purged with N2, then potassium phosphate iN (0.726 mL, 0.726 mmol) was added. The mixture was degassed and purged with N2 again, then warmed to 80°C and stirred for 3 h. Then the reaction mixture was diluted with EtOAc, filtered through a CeliteTM plug and concentrated invacuo. The resulting residue was purified by column chromatography over silica gel (24g, eluting with Hexanes/EtOAc (100:0 to 0:100)) to give (25,3R)-methyl 3-cyclopropyl-3-(2-(2-((2,2- dimethylpyrrolidin- 1 -yl)methyl)-4-(2-methoxypyridin-4-yl)phenyl)chroman-7-yl)-2- methylpropanoate.
Same Skeleton Products
Historical Records

Related Functional Groups of
[ 762262-09-9 ]

Organoboron

Chemical Structure| 163105-89-3

[ 163105-89-3 ]

(6-Methoxypyridin-3-yl)boronic acid

Similarity: 0.87

Chemical Structure| 612845-44-0

[ 612845-44-0 ]

(6-Ethoxypyridin-3-yl)boronic acid

Similarity: 0.84

Chemical Structure| 1043869-98-2

[ 1043869-98-2 ]

5-Fluoro-2-methoxypyridine-4-boronic acid

Similarity: 0.81

Chemical Structure| 475275-69-5

[ 475275-69-5 ]

(5-Chloro-2-methoxypyridin-4-yl)boronic acid

Similarity: 0.81

Chemical Structure| 163105-90-6

[ 163105-90-6 ]

2-Methoxy-3-pyridineboronic acid

Similarity: 0.78

Ethers

Chemical Structure| 163105-89-3

[ 163105-89-3 ]

(6-Methoxypyridin-3-yl)boronic acid

Similarity: 0.87

Chemical Structure| 612845-44-0

[ 612845-44-0 ]

(6-Ethoxypyridin-3-yl)boronic acid

Similarity: 0.84

Chemical Structure| 1043869-98-2

[ 1043869-98-2 ]

5-Fluoro-2-methoxypyridine-4-boronic acid

Similarity: 0.81

Chemical Structure| 475275-69-5

[ 475275-69-5 ]

(5-Chloro-2-methoxypyridin-4-yl)boronic acid

Similarity: 0.81

Chemical Structure| 163105-90-6

[ 163105-90-6 ]

2-Methoxy-3-pyridineboronic acid

Similarity: 0.78

Related Parent Nucleus of
[ 762262-09-9 ]

Pyridines

Chemical Structure| 163105-89-3

[ 163105-89-3 ]

(6-Methoxypyridin-3-yl)boronic acid

Similarity: 0.87

Chemical Structure| 612845-44-0

[ 612845-44-0 ]

(6-Ethoxypyridin-3-yl)boronic acid

Similarity: 0.84

Chemical Structure| 1043869-98-2

[ 1043869-98-2 ]

5-Fluoro-2-methoxypyridine-4-boronic acid

Similarity: 0.81

Chemical Structure| 475275-69-5

[ 475275-69-5 ]

(5-Chloro-2-methoxypyridin-4-yl)boronic acid

Similarity: 0.81

Chemical Structure| 163105-90-6

[ 163105-90-6 ]

2-Methoxy-3-pyridineboronic acid

Similarity: 0.78