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[ CAS No. 1246765-32-1 ] {[proInfo.proName]}

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Chemical Structure| 1246765-32-1
Chemical Structure| 1246765-32-1
Structure of 1246765-32-1 * Storage: {[proInfo.prStorage]}
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Product Details of [ 1246765-32-1 ]

CAS No. :1246765-32-1 MDL No. :MFCD18383504
Formula : C15H21BO5 Boiling Point : -
Linear Structure Formula :- InChI Key :HGVNIRYMFIJLJQ-UHFFFAOYSA-N
M.W : 292.14 Pubchem ID :24824491
Synonyms :

Calculated chemistry of [ 1246765-32-1 ]

Physicochemical Properties

Num. heavy atoms : 21
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.53
Num. rotatable bonds : 4
Num. H-bond acceptors : 5.0
Num. H-bond donors : 0.0
Molar Refractivity : 80.69
TPSA : 53.99 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) : -6.14 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.0
Log Po/w (XLOGP3) : 2.73
Log Po/w (WLOGP) : 1.78
Log Po/w (MLOGP) : 1.23
Log Po/w (SILICOS-IT) : 1.83
Consensus Log Po/w : 1.52

Druglikeness

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

Water Solubility

Log S (ESOL) : -3.32
Solubility : 0.14 mg/ml ; 0.00048 mol/l
Class : Soluble
Log S (Ali) : -3.52
Solubility : 0.0886 mg/ml ; 0.000303 mol/l
Class : Soluble
Log S (SILICOS-IT) : -4.19
Solubility : 0.0187 mg/ml ; 0.0000641 mol/l
Class : Moderately soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 0.0
Synthetic accessibility : 3.18

Safety of [ 1246765-32-1 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P264-P270-P271-P280-P301+P312-P302+P352-P304+P340-P330-P363-P501 UN#:N/A
Hazard Statements:H302-H312-H332 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 1246765-32-1 ]

* 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 [ 1246765-32-1 ]

[ 1246765-32-1 ] Synthesis Path-Downstream   1~35

  • 3
  • [ 17100-63-9 ]
  • [ 73183-34-3 ]
  • 3-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid methyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 80℃; for 4h;Inert atmosphere; A mixture of <strong>[17100-63-9]methyl 4-bromo-3-methoxybenzoate</strong> (3.0 g, 12.2 mmol), 4,4,5,5-tetramethyl-2- (4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-l,3,2-dioxaborolane (4.8 g, 19 mmol), Pd(dppf)Ch (450 mg, 0.6 mmol) and potassium acetate (1.9 g, 19.0 mmol) in dioxane (50 mL) was stirred at 80 C under an N2 atmosphere for 4 h. The reaction was filtered through a pad of Celite, and the filter cake washed with EtOAc (10 mL x 3). The filtrate was concentrated under vacuum and the residue purified by silica gel column chromatography using 15: 1 petroleum ether/ethyl acetate to afford methyl 3-methoxy-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2- yl)benzoate (2.5 g, 70% yield) as a white solid. MS Calcd.: 292.1, MS Found: 293.4 [M+l] +.
69% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 80℃; for 16h;Inert atmosphere; methyl 3-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (0285) To a solution of <strong>[17100-63-9]methyl 4-bromo-3-methoxybenzoate</strong> (7.3 g, 29.79 mmol) in dioxane (150 mL) was added 4,4,5,5-tetramethyl-2-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane (8.3 g, 32.69 mmol), Pd(dppf)Cl2.CH2Cl2 (2.4 g, 2.94 mmol) and potassium acetate (8.76 g, 89.26 mmol) at room temperature. The reaction mixture was stirred for 16 h at 80 C., cooled to room temperature, and treated with water (100 mL). The resulting solution was extracted with ethyl acetate (250 mL×3). The organic phases were combined, washed with brine and dried over sodium sulfate. The solvent was removed under reduced pressure and the residue was purified by flash chromatography eluting with ethyl acetate in hexane (0% to 10% gradient) to yield methyl 3-methoxy-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate as yellow oil (6.0 g, 69%). MS: m/z=293.0 [M+H]+.
50% With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; at 100℃; for 1h;Microwave irradiation; Inert atmosphere; Sealed tube; Preparation 19: methyl 3-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)benzoate; 1 ,1 '-Bis(diphenylphospino)ferrocene-palladium dichloride (157 mg, 0.204 mmol), <strong>[17100-63-9]methyl 4-bromo-3-methoxybenzoate</strong> (1000 mg, 4.08 mmol), bis(pinacolato)diboron (1140 mg, 4.49 mmol), potassium acetate (843 mg, 8.16 mmol) and dioxane (3 ml_) were combined in a microwave vial and bubbled with nitrogen for 5 min. The vial was sealed and heated to 1000C in a microwave reactor for 60 min. The reaction was cooled to room temperature, filtered through celite and partitioned between ethyl acetate (10 mL) and water (10 mL). The phases were separated. The organic phase was dried over magnesium sulfate, filtered and concentrated to give an off-white solid. The solid was purified by silica gel column chromatography eluting with a gradient of 0%-50% ethyl acetate/ heptane to obtain the title compound (600 mg, 50 %) 1 H NMR (400 MHz,DMSO-cfe) delta ppm 1.26 (s, 12 H) 3.78 (s, 3 H) 3.84 (s, 3 H) 7.41 (d, J=1.37 Hz, 1 H) 7.50 (dd, J=7.61 , 1.37 Hz, 1 H) 7.62 (d, J=7.61 Hz, 1 H).
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 100℃; for 6h;Inert atmosphere; General procedure: Preparation 3 7-Cvclopropyl-4-r4-fluoro-3-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)phenyll-7/-/- imidazor4,5-clpyridazine A mixture of 4-(3-bromo-4-fluorophenyl)-7-cyclopropyl-7/-/-imidazo[4,5-c]pyridazine (Preparation 8, 820 mg, 2.461 mmol), bispinacolatodiboron (938 mg, 3.692 mmol) and potassium acetate (483 mg, 4.922 mmol) in dioxane (20 ml_) was degassed with nitrogen before the addition of 1 ,1 '-bis(di-phenylphosphino)ferrocene palladium (II) dichloride (201 mg, 0.246 mol). The reaction was heated to 100C for 3 hours before cooling and filtering through celite, washing with EtOAc. The filtrate was concentrated in vacuo and purified using silica gel column chromatography eluting with 0-2% MeOH in EtOAc followed by trituration with EtOAc to afford the title compound as an off-white solid (510 mg, 55%). 1 H NMR (400 MHz, CDCI3): delta ppm 1.25-1.34 (m, 4H), 1.39 (s, 12H), 3.67-3.73 (m, 1 H), 7.21-7.26 (s, 1 H), 8.25 (s, 1 H), 8.40-8.44 (m, 2H), 9.40 (s, 1 H). MS m/z 299 [M+H]+ Boronic acid, MS m/z 381 [M+H]+ Boronate ester
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In toluene; at 110℃; for 3h;Inert atmosphere; Compound 61-1 (200 mg, 0.816 mmol),Bis (pinacolato) diboron(246 mg, 0.979 mmol), Pd (dppf) 2Cl2 (66 mg, 0.0816 mmol) and potassium acetate (240 mg, 2.448 mmol) were dissolved in 20 mL of toluene,Nitrogen replacement 3 times,Heated to 110 C,The mixture was reacted for 3 hours,Cooled to room temperature,filter,The filtrate was used directly in the next step without separation.

  • 4
  • [ 1246765-32-1 ]
  • [ 1407964-95-7 ]
  • [ 1831863-09-2 ]
YieldReaction ConditionsOperation in experiment
258 mg With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In 1,4-dioxane; water at 80℃; Inert atmosphere; 30 4.7. General procedure for Suzuki coupling of on 6-bromothieno[2,3-d]pyrimidines General procedure: Compounds II (200-1000 mg) were mixed with the selected boronic acid (1.2 eq), fine powdered K2CO3 (3 eq), Pd(PPh3)4 (0.01 eq) and 1,4-dioxane/water (1/1 by vol.%, 4-8 mL). The reaction was then stirred at 80 C for 2-5 h under nitrogen atmosphere.The solvent was removed and the product was diluted with water(25-50 mL) and extracted with Et2O or EtOAc (25-100 mL), the water phase was extracted with more diethyl ether or EtOAc (2 x 25 mL). The combined organic phases were washed with saturated aq NaCl solution (25 mL), dried over anhydrous Na2SO4,filtered and concentrated in vacuo. Purification was performed as specified for each individual compound. 4.7.30 Methyl (R)-3-methoxy-4-(4-((1-phenylethyl)amino)thieno[2,3-d]pyrimidin-6-yl)benzoate (30b) fx40 Compound 30b was prepared as described in Section 4.7 using compound IIb (231 mg, 0.691 mmol) and methyl 3-methoxy-4-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (300 mg, 1.027 mmol). The crude product was purified using silica-gel column chromatography (EtOAc/n-pentane, 3/2), Rf = 0.17. This gave 258 mg (0.615 mmol, 89%) of 30b as a yellow crystalline solid, mp. 126-127 °C; HPLC purity: 98%, tR = 29.0 min; [α]D20 = -434.2 (c 1.00, DMSO); 1H NMR (600 MHz, DMSO-d6) δ: 8.42 (s, 1H), 8.32 (d, J = 7.9, 1H), 8.30 (s, 1H), 7.92-7.89 (m, 1H), 7.72-7.69 (m, 1H), 7.67-7.66 (m, 1H), 7.45-7.42 (m, 2H), 7.35-7.31 (m, 2H), 7.24-7.21 (m, 1H), 5.57-5.51 (m, 1H), 4.03 (s, 3H), 3.89 (s, 3H), 1.58 (d, J = 7.0, 3H); 13C NMR (150 MHz, DMSO-d6) δ: 166.2, 165.7, 155.8, 155.2, 154.1, 144.6, 132.4, 130.1, 128.3 (2C), 127.8, 126.7, 126.5, 126.1 (2C), 122.0, 118.9, 116.0, 112.6, 56.1, 52.3, 49.0, 22.5; IR (neat, cm-1): 3248, 2970, 2930, 1714, 1576, 1294, 1229, 758, 697; HRMS (APCI/ASAP, m/z): 420.1375 (calcd. C23H22N3O3S, 420.1382, [M+H]+).
  • 5
  • [ 56256-14-5 ]
  • 3-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid methyl ester [ No CAS ]
  • 6
  • [ 17100-63-9 ]
  • [ 25015-63-8 ]
  • 3-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid methyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; dichloro bis(acetonitrile) palladium(II); triethylamine; In 1,4-dioxane; at 80℃;Inert atmosphere; General procedure: The methyl benzoate (200-1500 mg), PdCl2(CH3CN)2 (0.02 eq)and SPhos (0.08 eq) were added to a pressure tube. Then, 1,4-dioxane (0.5-3.5 mL) and Et3N (0.5-2 mL) were added under N2 atmosphere, followed by dropwise addition of HBpin (1.5 eq) while stirring under N2 atmosphere. The reaction mixture was heated to 80 C and stirred for 5-20 h. After cooling to rt, the reaction mixturewas filtered through a Celite pad. If further purificationwasperformed, it is specified in each specific example. 4.6.3 Methyl 3-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate fx9 The target compound was prepared as described in Section 4.6 , starting with <strong>[17100-63-9]methyl 4-bromo-3-methoxybenzoate</strong> (501 mg, 2.05 mmol). The crude oil (600 mg) was used without further purification. 1H NMR spectroscopy confirmed the presence of 54% of the desired product by comparison with the literature [54] . 1H NMR (600 MHz, DMSO-d6) delta: 7.65-7.63 (m, 1H), 7.54-7.52 (m, 1H), 7.44-7.43 (m, 1H), 3.86 (s, 3H), 3.80 (s, 3H), 1.28 (s, 12H).
  • 7
  • [ 1246765-32-1 ]
  • [ 1831863-24-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: potassium carbonate; tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane; water / 80 °C / Inert atmosphere 2: methanol / Reflux; Inert atmosphere
  • 8
  • [ 1246765-32-1 ]
  • [ 1840966-79-1 ]
  • [ 1840966-81-5 ]
YieldReaction ConditionsOperation in experiment
43% With palladium diacetate; potassium carbonate; XPhos In tert-Amyl alcohol; water at 110℃; for 183h; Inert atmosphere; 10 Preparation 10 Methyl 5'-(7-ethyl-7H-imidazo[4,5-clpyridazin-4-yl)-2'-fluoro-2-methoxybiphenyl-4- carboxylate and 5'-(7-ethyl-7H-imidazor4,5-clpyridazin-4-yl)-2'-fluoro-2- methoxybiphenyl-4-carboxylic acid Preparation 10 Methyl 5'-(7-ethyl-7H-imidazo[4,5-clpyridazin-4-yl)-2'-fluoro-2-methoxybiphenyl-4- carboxylate and 5'-(7-ethyl-7H-imidazor4,5-clpyridazin-4-yl)-2'-fluoro-2- methoxybiphenyl-4-carboxylic acid 7-Ethyl-4-(4-fluoro-3-chlorophenyl)-7/-/-imidazo[4,5-c]pyridazine (Preparation 7, 200 mg, 0.723 mmol), methyl-3-methoxy-4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2- yl)benzoate (Preparation 29, 300 mg, 1.027 mmol) dicyclohexyl(2',4',6'-triisopropyl- [1 , 1'-biphenyl]-2-yl)phosphine (35 mg, 0.073 mmol), palladium (II) acetate (8 mg, 0.036 mmol) and potassium carbonate (280 mg, 2.029 mmol) were mixed in 2-methyl- 2-butanol (6 ml_) and water (3 ml_) under nitrogen and heated to 110°C for 18 hours. The reaction was cooled and partitioned between water (50 ml_) and EtOAc (50 ml_). The aqueous layer was separated and extracted further with EtOAc (10 ml_). The combined organic layers were dried over sodium sulphate and concentrated in vacuo. The residue was triturated with tert-butylmethylether (2 ml_) to afford methyl 5'- (7-ethyl-7H-imidazo[4,5-c]pyridazin-4-yl)-2'-fluoro-2-methoxybiphenyl-4-carboxylate (125 mg, 43%). 1 H NMR (400 MHz, CDCI3): δ ppm 1 .69 (t, 3H), 3.89 (s, 3H), 3.96 (s, 3H), 4.55-4.61 (q, 2H), 7.35 (t, 1 H), 7.43 (d, 1 H), 7.69 (s, 1 H), 7.75 (d, 1 H), 8.22-8.24 (dd, 1 H), 8.28- 8.33 (m, 2H), 9.39 (s, 1 H). 19F NMR (376 MHz, CDCI3): δ ppm -110.5 MS m/z 407 [M+H]+ The combined aqueous layers were acidified with 1 M aqueous citric acid to pH=4 and extracted with EtOAc twice (50 ml_, 10 ml_). The combined organic layers were dried over sodium sulphate and concentrated in vacuo. The residue was triturated with tert- butyldimethylether to afford 5'-(7-ethyl-7H-imidazo[4,5-c]pyridazin-4-yl)-2'-fluoro-2- methoxybiphenyl-4-carboxylic acid (125 mg, 43%). 1 H NMR (400 MHz, DMSO-d6): δ ppm 1.53 (t, 3H), 3.82 (s, 3H), 4.46-4.52 (q, 2H), 7.46-7.53 (m, 2H), 7.62-7.68 (m, 2H), 8.44-8.49 (m, 2H), 8.85 (s, 1 H), 9.54 (s, 1 H). 19F NMR (376 MHz, CDCI3): δ ppm -11 1.5 MS m/z 393 [M+H]+ Methyl 5'-(7-ethyl-7H-imidazo[4,5-c]pyridazin-4-yl)-2'-fluoro-2-methoxybiphenyl-4- carboxylate may also be prepared according to the following method: A solution of 7-ethyl-4-[4-fluoro-3-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)phenyl]- 7H-imidazo[4,5-c]pyridazine (Preparation 4, 50 mg, 0.136 mmol) and methyl-3- bromo-4-methoxybenzoate (33 mg, 0.136 mmol) in DIPEA (0.4 ml_) and DMF (2 ml_) was degassed with nitrogen before the addition of bis (tri-tert- butylphosphine)palladium (0) (7 mg,0.014 mmol) and heating to 90°C for 18 hours. The reaction was cooled, diluted with EtOAc (20 ml_) and washed with brine (20 ml_). The organic layer was collected, concentrated in vacuo and purified using silica gel column chromatography eluting with EtOAc to afford the title compound. 5'-(7-ethyl-7H-imidazo[4,5-c]pyridazin-4-yl)-2'-fluoro-2-methoxybiphenyl-4-carboxylic acid may also be prepared according to the following method: A mixture of methyl 5'-(7-ethyl-7H-imidazo[4,5-c]pyridazin-4-yl)-2'-fluoro-2- methoxybiphenyl-4-carboxylate (55 mg, 0.136 mmol) and LiOH (3.6 mg, 0.150 mmol) in THF (2 ml_) and water (1 ml_) was stirred at room temperature for 3 hours. Further LiOH (7.2 mg, 0.299 mmol) was added and the reaction stirred at room temperature for 18 hours. The reaction was concentrated in vacuo, dissolved in DCM and 1 M HCI was added until pH=7. The organic layer was separated, the aqueous layer extracted with DCM, and the organic extracts combined, dried over Na2S04 and concentrated in vacuo to afford the title compound.
  • 9
  • [ 1246765-32-1 ]
  • [ 1840966-74-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: potassium carbonate; palladium diacetate; XPhos / water; tert-Amyl alcohol / 183 h / 110 °C / Inert atmosphere 2: methanol; ethanol / 18 h / 75 °C
  • 10
  • [ 1246765-32-1 ]
  • [ 1840966-82-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: potassium carbonate; palladium diacetate; XPhos / water; tert-Amyl alcohol / 183 h / 110 °C / Inert atmosphere 2: citric acid / water / pH 4
  • 11
  • [ 1246765-32-1 ]
  • [ 1840966-75-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: potassium carbonate; palladium diacetate; XPhos / water; tert-Amyl alcohol / 183 h / 110 °C / Inert atmosphere 2.1: citric acid / water / pH 4 3.1: oxalyl dichloride / N,N-dimethyl-formamide; dichloromethane / 2.5 h / 20 °C 3.2: 48 h / 20 °C / Cooling with ice
  • 12
  • [ 1246765-32-1 ]
  • [ 1926991-46-9 ]
  • [ 1926991-74-3 ]
YieldReaction ConditionsOperation in experiment
26% With potassium phosphate; bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II) In 1,4-dioxane; water at 90℃; for 2h; 79.2 Step 2:methyl 4- [6- j(E)-but-2-enyll-7-oxo-1 -(p-tolylsulfonyi)pyrrolo [2,3-c] pyridin-4-yIj -3- methoxy-beuzoate Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropafladium(TT) (141 mg, 0.2 mmol) was added to a mixture of 4-bromo-6-[(E)-but-2-enylj-1 -(p-tolylsulfonyl)pyrrolo[2,3- cpyridin-7-one (Step 1, 1.52 g, 3.6 nimol) and methyl 3-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (1.56 g, 5.3 mmol) in 1,4-dioxane (10 mL) and 2 M potassium phosphate tribasic in water (3 equiv., 10.7 mmol). The reaction was heated to 90°C for 2 h. The reaction was cooled to room temperature, diluted with ethyl acetate, and washed with water. The organic solution was dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (10-35% ethyl acetate: heptanes) to yield title compound (470 mg, 26%). LCMS M/Z (M+H) 507.
With potassium phosphate; bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II) In 1,4-dioxane; water at 90℃; for 2h; Sealed tube; Step 2: methyl 4-[6-[(E)-but-2-enyl]-7-oxo-1-(p-tolylsulfonyl)pyrrolo[2,3-c]pyridin-4-yl]benzoate (19) General procedure: To an 8 mL vial was added 4-bromo-6-[(E)-but-2-enyl]-1-(ptolylsulfonyl)pyrrolo[2,3-c]pyridin-7-one (250 mg. 0.59 mmol), 1,4-dioxane (2 mL), methyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (233 mg, 0.89 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (21 mg, 0.030 mmol), and potassiumphosphate tribasic (2.0 M in water, 0.89 mL, 1.8 mmol). The reaction was capped and shaken for2h at 90 °C. The reaction was cooled to room temperature, and extracted with ethyl acetate. Theaqueous was further extracted with ethyl acetate, then the combined organics were dried oversodium sulfate and concentrated under reduced pressure. The crude was purified by flash column(30-80% ethyl acetate : heptanes) yielding desired product (185 mg, 65% yield).
  • 13
  • [ 1246765-32-1 ]
  • [ 1071540-54-9 ]
  • [ 2058322-50-0 ]
YieldReaction ConditionsOperation in experiment
79% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium hydrogencarbonate In 1,4-dioxane; water at 100℃; for 10h; Inert atmosphere; 14 methyl 4-(7-chlorofuro[3,2-b]pyridin-2-yl)-3-methoxybenzoate methyl 4-(7-chlorofuro[3,2-b]pyridin-2-yl)-3-methoxybenzoate (0286) To a solution of methyl 3-methoxy-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (5.0 g, 17.12 mmol) in dioxane (210 mL) were added 7-chloro-2-iodofuro[3,2-b]pyridine (4.7 g, 16.82 mmol), Pd(dppf)Cl2.CH2Cl2 (1.4 g, 1.71 mmol), sodium bicarbonate (1.5 g, 17.86 mmol) and water (70 mL) at room temperature. The reaction mixture was stirred for 10 h at 100° C. After cooling to room temperature, it was quenched by the addition of water (150 mL). The resulting solution was extracted with ethyl acetate (250 mL×3). The organic phases were combined, washed with brine and dried over sodium sulfate. The solvent was removed under reduced pressure and the residue was purified by flash chromatography eluting with methanol in dichloromethane (0% to 10% gradient) to yield methyl 4-[7-chlorofuro[3,2-b]pyridin-2-yl]-3-methoxybenzoate as brown solid (4.3 g, 79%). MS: m/z=318.0 [M+H]+.
  • 14
  • [ 1246765-32-1 ]
  • [ 2058322-51-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium hydrogencarbonate / water; 1,4-dioxane / 10 h / 100 °C / Inert atmosphere 2: sodium hydrogencarbonate; tetrakis(triphenylphosphine) palladium(0) / water; 1,4-dioxane / 2 h / 100 °C / Inert atmosphere
  • 15
  • [ 1246765-32-1 ]
  • [ 2058322-52-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium hydrogencarbonate / water; 1,4-dioxane / 10 h / 100 °C / Inert atmosphere 2: potassium acetate; (bis(tricyclohexyl)phosphine)palladium(II) dichloride / water; N,N-dimethyl-formamide / 16 h / 100 °C / Inert atmosphere
  • 16
  • [ 1246765-32-1 ]
  • [ 2058269-01-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium hydrogencarbonate / water; 1,4-dioxane / 10 h / 100 °C / Inert atmosphere 2: potassium acetate; (bis(tricyclohexyl)phosphine)palladium(II) dichloride / water; N,N-dimethyl-formamide / 16 h / 100 °C / Inert atmosphere 3: sodium hydroxide / water; methanol / 16 h / 20 °C / Inert atmosphere
  • 17
  • [ 1246765-32-1 ]
  • [ 2058268-97-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium hydrogencarbonate / water; 1,4-dioxane / 10 h / 100 °C / Inert atmosphere 2: sodium hydrogencarbonate; tetrakis(triphenylphosphine) palladium(0) / water; 1,4-dioxane / 2 h / 100 °C / Inert atmosphere 3: sodium hydroxide / water; methanol / 16 h / 20 °C / Inert atmosphere
  • 18
  • [ 1246765-32-1 ]
  • [ 2058265-93-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium hydrogencarbonate / water; 1,4-dioxane / 10 h / 100 °C / Inert atmosphere 2: sodium hydrogencarbonate; tetrakis(triphenylphosphine) palladium(0) / water; 1,4-dioxane / 2 h / 100 °C / Inert atmosphere 3: sodium hydroxide / water; methanol / 16 h / 20 °C / Inert atmosphere 4: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 20 °C / Inert atmosphere
  • 19
  • [ 1246765-32-1 ]
  • [ 1807629-50-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / water; toluene / 3 h / 110 °C / Inert atmosphere 2.1: sodium tris(acetoxy)borohydride / 1 h / 40 °C 2.2: 1 h / 40 °C
  • 20
  • [ 1246765-32-1 ]
  • [ 1807629-51-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / water; toluene / 3 h / 110 °C / Inert atmosphere 2.1: sodium tris(acetoxy)borohydride / 1 h / 40 °C 2.2: 1 h / 40 °C 3.1: water; lithium hydroxide / methanol / 20 °C
  • 21
  • [ 1246765-32-1 ]
  • [ 1807629-52-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / water; toluene / 3 h / 110 °C / Inert atmosphere 2.1: sodium tris(acetoxy)borohydride / 1 h / 40 °C 2.2: 1 h / 40 °C 3.1: water; lithium hydroxide / methanol / 20 °C 4.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 2 h / 20 °C
  • 22
  • [ 1246765-32-1 ]
  • [ 1807628-91-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / water; toluene / 3 h / 110 °C / Inert atmosphere 2.1: sodium tris(acetoxy)borohydride / 1 h / 40 °C 2.2: 1 h / 40 °C 3.1: water; lithium hydroxide / methanol / 20 °C 4.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 2 h / 20 °C 5.1: boron tribromide / dichloromethane / -10 °C
  • 23
  • [ 1246765-32-1 ]
  • [ 54949-01-8 ]
  • [ 1807629-49-7 ]
YieldReaction ConditionsOperation in experiment
45.4% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride In water; toluene at 110℃; for 3h; Inert atmosphere; 61 Intermediate 61-4: 4-(8-formyl-6,7-dihydro-5H-benzo[d]cyclohepten-9-yl)-3-methoxybenzoic acid methyl ester 61-2 of the compound obtained in the next step was dissolved in 20 mL of toluene,61-3 (58 mg, 0.0718 mmol) was added successively,(211 mg, 2.15 mmol) and Pd (dppf) 2Cl2 (58 mg, 0.0718 mmol)Nitrogen replacement 3 times,Add 3 mL of water,Replace again 3 times,Heated to 110 ° C,Reflux for about 3 hours,Spin dry,Column chromatography yielded 61-4(110 mg, 45.5%).
  • 24
  • [ 1246765-32-1 ]
  • [ 51865-32-8 ]
  • [ 2417112-63-9 ]
YieldReaction ConditionsOperation in experiment
86% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In 1,4-dioxane; water at 100℃; for 4h; Inert atmosphere; Methyl 3-methoxy-4-(3-oxocyclopent-l-enyl)benzoate. A mixture of methyl 3- methoxy-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)benzoate (2.5 g, 8.6 mmol), 3- bromocyclopent-2-en-l-one (1.3 g, 8.6 mmol), Pd(PPh3)4 (500 mg, 0.43 mmol) and potassium carbonate (1.8 g, 12.9 mmol) in dioxane (50 mL) and water (10 mL) was stirred at 100 °C under an N2 atmosphere for 4 h. The reaction was filtered through a pad of Celite and the filter cake washed with EtOAc (10 mL x 3). The filtrate was concentrated under vacuum and the residue purified by silica gel column chromatography using 3: 1 petroleum ether/ethyl acetate to afford methyl 3-methoxy-4-(3-oxocyclopent-l-enyl)benzoate (1.8 g, 86% yield) as ayellowish solid. MS Calcd.: 246.1, MS Found: 247.4 [M+l] +.
  • 25
  • [ 1246765-32-1 ]
  • [ 2555014-92-9 ]
  • [ 2555016-21-0 ]
YieldReaction ConditionsOperation in experiment
58% With palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; anhydrous sodium carbonate In 1,4-dioxane at 90℃; for 1.5h; Inert atmosphere; 1 Step 1. 4-[1-(2,2-dimethylpropanoyl)-5-(4-fluorophenyl)-6-isopropyl-pyrrolo[2,3-f]indazol-7-yl]-3-methoxy-benzoate (C76) To a solution of 1-[5-(4-fluorophenyl)-7-iodo-6-isopropyl-pyrrolo[2,3-f]indazol-1-yl]-2,2-dimethyl-propan-1-one S7 (4.90 g, 9.50 mmol), methyl 3-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (5.11 g, 17.5 mmol), and Pd(dppf)Cl2 (604 mg, 0.74 mmol) in 1,4-dioxane (43 mL) was added sodium carbonate (17 mL of 2 M, 34 mmol). The reaction mixture was purged with nitrogen and the solution was stirred at 90° C. for 90 min. Water (100 mL) and dichloromethane (100 mL) were added and the mixture was extracted with dichloromethane (3*100 mL). The organic layers were combined, passed through a phase separator and concentrated in vacuo. Purification by silica gel column chromatography (Eluent: 0-100% dichloromethane in heptane). To a solution of pure material in dichloromethane (150 mL) was added MP-TMT palladium scavenging resin (3.09 g). The suspension was stirred overnight at room temperature. The mixture was filtered, washed with dichloromethane, and concentrated in vacuo to afford the product (2.98 g, 58%). LCMS m/z 542.5 [M+H]+.
58% With palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; anhydrous sodium carbonate In 1,4-dioxane at 90℃; for 1.5h; 4.1 Step 1. 4-[l -(2,2-dimethylpropanoyl)-5-(4fluorophenyl)-6-isopropyl-pyrrolo[2,3f]indazol-7- yl]-3-methoxy-benzoate (C76) To a solution of l-[5-(4-fluorophenyl)-7-iodo-6-isopropyl-pyrrolo[2,3-f]indazol-l-yl]- (0965) 2.2-dimethyl-propan-l-one S7 (4.90 g, 9.50 mmol), methyl 3-methoxy-4-(4,4,5,5-tetramethyl- (0966) 1.3.2-dioxaborolan-2-yl)benzoate (5.11 g, 17.5 mmol), and Pd(dppf)Ch (604 mg, 0.74 mmol) in 1,4-dioxane (43 mL) was added sodium carbonate (17 mL of 2 M, 34 mmol). The reaction mixture was purged with nitrogen and the solution was stirred at 90 °C for 90 min. Water (100 mL) and dichloromethane (100 mL) were added and the mixture was extracted with dichloromethane (3 x 100 mL). The organic layers were combined, passed through a phase separator and concentrated in vacuo. Purification by silica gel column chromatography (Eluent: 0-100 % dichloromethane in heptane). To a solution of pure material in dichloromethane (150 mL) was added MP-TMT palladium scavenging resin (3.09 g). The suspension was stirred overnight at room temperature. The mixture was filtered, washed with dichloromethane, and concentrated in vacuo to afford the product (2.98 g, 58 %). LCMS m/z 542.5 [M+H]+.
58% With palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; anhydrous sodium carbonate In 1,4-dioxane at 90℃; for 1.5h; 4.1 Step 1. 4-[l -(2,2-dimethylpropanoyl)-5-(4fluorophenyl)-6-isopropyl-pyrrolo[2,3f]indazol-7- yl]-3-methoxy-benzoate (C76) To a solution of l-[5-(4-fluorophenyl)-7-iodo-6-isopropyl-pyrrolo[2,3-f]indazol-l-yl]- (0965) 2.2-dimethyl-propan-l-one S7 (4.90 g, 9.50 mmol), methyl 3-methoxy-4-(4,4,5,5-tetramethyl- (0966) 1.3.2-dioxaborolan-2-yl)benzoate (5.11 g, 17.5 mmol), and Pd(dppf)Ch (604 mg, 0.74 mmol) in 1,4-dioxane (43 mL) was added sodium carbonate (17 mL of 2 M, 34 mmol). The reaction mixture was purged with nitrogen and the solution was stirred at 90 °C for 90 min. Water (100 mL) and dichloromethane (100 mL) were added and the mixture was extracted with dichloromethane (3 x 100 mL). The organic layers were combined, passed through a phase separator and concentrated in vacuo. Purification by silica gel column chromatography (Eluent: 0-100 % dichloromethane in heptane). To a solution of pure material in dichloromethane (150 mL) was added MP-TMT palladium scavenging resin (3.09 g). The suspension was stirred overnight at room temperature. The mixture was filtered, washed with dichloromethane, and concentrated in vacuo to afford the product (2.98 g, 58 %). LCMS m/z 542.5 [M+H]+.
  • 26
  • [ 1246765-32-1 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: palladium dichloride; triphenylphosphine; potassium carbonate / 1,4-dioxane; water / 24 h / 105 °C / Inert atmosphere 2: sodium hydroxide / water; MeOH; tetrahydrofuran / 80 °C
  • 27
  • [ 1246765-32-1 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: palladium dichloride; triphenylphosphine; potassium carbonate / 1,4-dioxane; water / 24 h / 105 °C / Inert atmosphere 2: sodium hydroxide / water; MeOH; tetrahydrofuran / 80 °C
  • 28
  • [ 1246765-32-1 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: palladium dichloride; triphenylphosphine; potassium carbonate / 1,4-dioxane; water / 24 h / 105 °C / Inert atmosphere 2: sodium hydroxide / water; MeOH; tetrahydrofuran / 80 °C
  • 29
  • [ 1246765-32-1 ]
  • [ 2758181-28-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: palladium dichloride; triphenylphosphine; potassium carbonate / 1,4-dioxane; water / 24 h / 105 °C / Inert atmosphere 2: sodium nitrite; acetic acid / water / 2 h / 20 °C 3: sodium hydroxide / water; MeOH; tetrahydrofuran / 80 °C
  • 30
  • [ 15155-41-6 ]
  • [ 1246765-32-1 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; triphenylphosphine; palladium dichloride In 1,4-dioxane; water at 105℃; for 24h; Inert atmosphere;
  • 31
  • [ 63224-42-0 ]
  • [ 1246765-32-1 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; triphenylphosphine; palladium dichloride In 1,4-dioxane; water at 105℃; for 24h; Inert atmosphere;
  • 32
  • [ 1246765-32-1 ]
  • [ CAS Unavailable ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; triphenylphosphine; palladium dichloride In 1,4-dioxane; water at 105℃; for 24h; Inert atmosphere;
  • 33
  • [ 1246765-32-1 ]
  • [ CAS Unavailable ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; triphenylphosphine; palladium dichloride In 1,4-dioxane; water at 105℃; for 24h; Inert atmosphere;
  • 34
  • [ 1246765-32-1 ]
  • [ CAS Unavailable ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: palladium dichloride; triphenylphosphine; potassium carbonate / 1,4-dioxane; water / 24 h / 105 °C / Inert atmosphere 2: sodium hydroxide / water; MeOH; tetrahydrofuran / 80 °C
  • 35
  • [ 1246765-32-1 ]
  • [ 69272-50-0 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; triphenylphosphine; palladium dichloride In 1,4-dioxane; water at 105℃; for 24h; Inert atmosphere;
Same Skeleton Products
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