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[ CAS No. 1185019-97-9 ] {[proInfo.proName]}

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Chemical Structure| 1185019-97-9
Chemical Structure| 1185019-97-9
Structure of 1185019-97-9 * Storage: {[proInfo.prStorage]}
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Product Details of [ 1185019-97-9 ]

CAS No. :1185019-97-9 MDL No. :MFCD22493858
Formula : C13H18BNO5 Boiling Point : -
Linear Structure Formula :- InChI Key :MTJSDUJKURLGMS-UHFFFAOYSA-N
M.W : 279.10 Pubchem ID :66708672
Synonyms :

Calculated chemistry of [ 1185019-97-9 ]

Physicochemical Properties

Num. heavy atoms : 20
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.54
Num. rotatable bonds : 3
Num. H-bond acceptors : 5.0
Num. H-bond donors : 0.0
Molar Refractivity : 78.23
TPSA : 73.51 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : Yes
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : Yes
Log Kp (skin permeation) : -6.08 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.0
Log Po/w (XLOGP3) : 2.71
Log Po/w (WLOGP) : 1.9
Log Po/w (MLOGP) : 0.37
Log Po/w (SILICOS-IT) : -0.29
Consensus Log Po/w : 0.94

Druglikeness

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

Water Solubility

Log S (ESOL) : -3.3
Solubility : 0.139 mg/ml ; 0.000499 mol/l
Class : Soluble
Log S (Ali) : -3.91
Solubility : 0.0346 mg/ml ; 0.000124 mol/l
Class : Soluble
Log S (SILICOS-IT) : -3.5
Solubility : 0.0879 mg/ml ; 0.000315 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 3.0 alert
Leadlikeness : 0.0
Synthetic accessibility : 3.26

Safety of [ 1185019-97-9 ]

Signal Word:Warning Class:
Precautionary Statements:P210-P261-P264-P271-P280-P302+P352-P304+P340-P305+P351+P338-P312-P332+P313-P337+P313-P362-P370+P378-P403+P233-P403+P235-P405-P501 UN#:
Hazard Statements:H315-H319-H335 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 1185019-97-9 ]

* 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 [ 1185019-97-9 ]

[ 1185019-97-9 ] Synthesis Path-Downstream   1~30

  • 1
  • [ 5344-78-5 ]
  • [ 73183-34-3 ]
  • [ 1185019-97-9 ]
YieldReaction ConditionsOperation in experiment
58% With potassium acetate In 1,4-dioxane at 100℃; for 18h; Inert atmosphere; 211.a 2-(2-Methoxy-4-nitro-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane; A mixture of 4-bromo-5-nitroanisole (5.0 g, 21.2 mmol), bis(pinacolato)diboron (8.21 g, 31.7 mmol) and potassium acetate (6.28 g, 63.3 mmol, dried on high vacuum at 100° C.) in dioxane (75 mL) was purged for 5 minutes with nitrogen. Bis(triphenylphosphine)palladium(II) chloride (1.48 g, 2.11 mmol) was added and the mixture was heated for 18 hours to 100° C. under nitrogen atmosphere. The mixture was diluted with ethyl acetate, washed with water and brine, dried over magnesium sulfate and the solvent was evaporated. Column chromatography (330 g silica, heptane/ethyl acetate 5-60%) afforded the title compound (3.46 g, 58%) as a light brown solid.MS EI (m/e): 279 [(M+)]. 1H NMR (CDCl3, 300 MHz): δ (ppm)=7.78 (s, 2H), 7.39 (s, 1H), 3.92 (s, 3H), 1.37 (s, 12H). Mp 75-78° C.
  • 2
  • [ 39806-90-1 ]
  • [ 1185019-97-9 ]
  • [ 1079178-14-5 ]
YieldReaction ConditionsOperation in experiment
58% With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In water; toluene; at 80℃; for 24h;Inert atmosphere; b) 4-(2-Methoxy-4-nitro-phenyl)-1-methyl-1H-pyrazole; A solution of 2-(2-methoxy-4-nitro-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (635 mg, 1.79 mmol) and <strong>[39806-90-1]1-methyl-4-iodo-1H-pyrazole</strong> (745 mg, 3.58 mmol) in ethanol (11 mL) and toluene (26 mL) was purged with argon for 5 minutes. 1,1'-bis(diphenylphosphino)ferrocene palladium (II) chloride (73.0 mg, 0.89 mmol) was added and the mixture was heated to 80 C., then 2M aqueous sodium carbonate solution (14 mL) was added and stirring at 80 C. was continued for further 24 hours. The mixture was diluted with ethyl acetate, washed with water and brine, dried over magnesium sulfate and the solvent was evaporated. Column chromatography (20 g silica, dichloromethane) afforded the title compound (245 mg, 58%) as a yellow solid. MS ISP (m/e): 234.0 [(M+H)+]. 1H NMR (DMSO, 300 MHz): delta (ppm)=8.35 (s, 1H), 8.08 (s, 1H), 7.85 (m, 3H), 4.03 (s, 3H), 3.90 (s, 3H). Mp 132-134 C.
  • 3
  • [ 77337-82-7 ]
  • [ 73183-34-3 ]
  • [ 1185019-97-9 ]
YieldReaction ConditionsOperation in experiment
100% With potassium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; at 80℃; for 5h;Inert atmosphere of nitrogen; A high pressure bottle was charged with [1 ,1 '-bis(diphenylphos- phino)ferrocene]-dichloropalladium(II) (1:1 complex with dichloromethane, 1.56 g, 2.15 mmol), potassium acetate (5.25 g, 22.5 mmol), l-bromo-2-methoxy-4- nitrobenzene (5.0 g, 21.5 mmol), bis(pinacolato)diboron (6.6 g, 25 mmol), and 1,4- dioxane ( 100 mL). The mixture was degassed by bubbling nitrogen through the solution. The bottle was capped and heated at 80 0C for 5 h. The resulting mixture was diluted with EtOAc (500 niL) and washed with 1 N aqueous HCl (500 mL). The organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo to afford 2-(2-methoxy-4-nitrophenyl)-4,4,5J5-tetramethyl- 1,3,2-dioxaborolane (7.0 g, 100 % yield) as a brown solid. The crude material was used for subsequent chemistry without purification.
97% With potassium acetate;bis-triphenylphosphine-palladium(II) chloride; In 1,4-dioxane; for 3h;Reflux; a) 2-(2-methoxy-4-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane; To a solution of <strong>[77337-82-7]1-bromo-2-methoxy-4-nitrobenzene</strong> (5.8 g, 25 mmol) in 1,4-dioxane (125 mL) was added bis(pinacolato)diboron (9.52 g, 37.5 mmol), potassium acetate (7.36 g, 75.0 mmol) and bis(triphenylphosphine)palladium(II) dichloride (877 mg, 1.25 mmol). Then the reaction mixture was stirred for 3 h at reflux. Water (150 mL) was added and the mixture was extracted twice with ethyl acetate (200 mL). The organic layers were washed with brine (150 mL), combined, dried over sodium sulfate, filtered off and evaporated. Flash chromatography of the residue (SiO2, heptane: EtOAc=4:1 to 0:1) afforded the title compound as yellow solid (6.78 g, 97%).MS ISP (m/e): 279.0 [(M)+]1H NMR (CDCl3, 300 MHz): delta (ppm)=7.78 (s, 2H), 7.65 (s, 1H) 3.92 (s, 3H), 1.37 (s, 9H), 1.26 (s, 3H).
97% With potassium acetate;bis-triphenylphosphine-palladium(II) chloride; In 1,4-dioxane; for 3h;Reflux; To a solution of l-bromo-2-methoxy-4-nitrobenzene (5.8 g, 25 mmol) in 1,4-dioxane (125 mL) was added bis(pinacolato)diboron (9.52 g, 37.5 mmol), potassium acetate (7.36 g, 75.0 mmol) and bis(triphenylphosphine)palladium(II) dichloride (877 mg, 1.25 mmol). Then the reaction mixture was stirred for 3h at refiux. Water (150 mL) was added and the mixture was extracted twice with ethyl acetate (200 mL). The organic layers were washed with brine (150 mL), combined, dried over sodium sulfate, filtered off and evaporated. Flash chromatography of the residue (Si02, heptane : EtOAc = 4: 1 to 0: 1) afforded the title compound as yellow solid (6.78g, 97%).MS ISP (m/e): 279.0 [(M)+]1H NMR (CDCI3, 300 MHz): delta (ppm) = 7.78 (s, 2H), 7.65 (s, 1H) 3.92 (s, 3H), 1.37 (s, 9H), 1.26 (s, 3H).
70% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 80℃; for 16h; 1 -Bromo-2-methoxy-4-nitrobenzene (4.00 g, 17.24 mmol), 4,4,4?,4?,5 ,5 ,5?,S?-octamethyl-2,2?-bi(1,3,2-dioxaborolane) (6.57 g, 25.9 mmol), potassium acetate (5.08 g, 51.7 mmol) and dioxane (100 mL) were combined. (1,1?- bis(diphenylphosphino)ferrocene)-dichloropalladium(II) dichioromethane complex (1 .418 g, 1.724 mmol) was added and the reaction mixture was heated at 80 C for 16h. The mixture was cooled to room temperature and was filtered through a pad ofdiatomaceous earth (Celite). The filtrate was transferred to a separatory funnel containing saturated aqueous NaHCO3 solution (100 mL). The aqueous layer was extracted with ethyl acetate (3 x 100 mL). The combined organic layers were washed with brine (50 mL), dried over MgSO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel (30% -* 70% ethylacetate in hexanes) to afford 2-(2-methoxy-4-nitrophenyl)-4,4,5 ,5 -tetramethyl- 1,3,2- dioxaborolane (3.35 g, 70% yield) as a light brown solid: ?H NMR (400 MHz, CDC13) oe 7.81 (d, J=1.0 Hz, 2 H), 7.69 (s, 1 H), 3.95 (s, 3 H), 1.39 (s, 12 H).

  • 4
  • [ 808773-39-9 ]
  • [ 1185019-97-9 ]
  • [ 1235492-36-0 ]
YieldReaction ConditionsOperation in experiment
49% With caesium carbonate In 1,4-dioxane; water at 110℃; for 2h; Inert atmosphere of nitrogen; L.2 A high pressure bottle was charged with 2-(2-methoxy-4- nitrophenyl)-4,4,5,54etramethyl-l,3,2-dioxaborolane (6.1 g, 13.8 mmol), [1,1'- bis(diphenylphosphino)ferrocene]-dichloropalladium(II) (1: 1 complex with dichloromethane, 1.0 g, 1.1 mmol), 4-bromo-6-methylpyridazine 1 -oxide (2.0 g, 11 mmol, B. Buettelmann et. al US Patent Application Publication 2004/0254179 Al)5 cesium carbonate (in 5 mL of water, 8.0 g, 21 mmol), and 1,4-dioxane (80 mL). The mixture was degassed by bubbling nitrogen through the solution. The bottle was capped and heated at 110 0C for 2 h. The resulting mixture was filtered through diatomaceous earth (Celite ). The filtrated was concentrated in vacuo. The crude product was purified using silica gel column chromatography (EtOAc/hexane) to afford 4-(2-methoxy-4-nitrophenyl)-6-methylpyridazine 1 -oxide (1.4 g, 49 % yield).
  • 5
  • [ 3435-25-4 ]
  • [ 1185019-97-9 ]
  • [ 1319068-75-1 ]
YieldReaction ConditionsOperation in experiment
99% With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; acetonitrile; for 3h;Inert atmosphere; Reflux; b) 4-(2-methoxy-4-nitrophenyl)-6-methylpyrimidine; To a solution of 2-(2-methoxy-4-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (6.78 g, 24.3 mmol) and <strong>[3435-25-4]4-chloro-6-methylpyrimidine</strong> (4.78 g, 36.4 mmol) in acetonitrile (272 mL) was added a solution of sodium carbonate (12.9 g, 121 mmol) in water (68 ml). This mixture was degassed and flushed with Ar and then tetrakis(triphenylphosphine)palladium(0) (1.4 g, 1.21 mmol) was added. It was stirred for 3 h at reflux and then poured onto water (300 mL). The mixture was extracted with ethyl acetate (350 mL) three times. The organic layers were washed with brine. (250 mL), combined, dried over sodium sulfate, filtered off and evaporated. Flash chromatography of the residue (SiO2, heptane: EtOAc=4:1 to 0:1) afforded the title compound yellow solid (5.92 g, 99%).MS ISP (m/e): 246.3 [(M+H)+]1H NMR (CDCl3, 300 MHz): delta (ppm)=9.20 (s, 1H), 8.12 (d, 1H), 7.96 (dd, 1H), 7.88 (d, 1H), 7.81 (s, 1H), 4.02 (s, 3H), 2.62 (s, 3H).
99% With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; acetonitrile; for 3h;Inert atmosphere; Reflux; To a solution of 2-(2-methoxy-4-nitrophenyl)-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (6.78 g, 24.3 mmol) and <strong>[3435-25-4]4-chloro-6-methylpyrimidine</strong> (4.78 g, 36.4 mmol) in acetonitrile (272 mL) was added a solution of sodium carbonate (12.9 g, 121 mmol) in water (68 ml). This mixture was degassed and flushed with Ar and then tetrakis(triphenylphosphine)palladium(0) (1.4 g, 1.21 mmol) was added. It was stirred for 3h at reflux and then poured onto water (300 mL). The mixture was extracted with ethyl acetate (350 mL) three times. The organic layers were washed with brine. (250 mL), combined, dried over sodium sulfate, filtered off and evaporated. Flash chromatography of the residue (Si02, heptane : EtOAc = 4: 1 to 0: 1) afforded the title compound yellow solid (5.92g, 99%).MS ISP (m/e): 246.3 [(M+H)+]1H NMR (CDCI3, 300 MHz): delta (ppm) = 9.20 (s, 1H), 8.12 (d, 1H), 7.96 (dd, 1H), 7.88 (d, 1H), 7.81 (s, 1H), 4.02 (s, 3H), 2.62 (s, 3H).
  • 6
  • [ 1185019-97-9 ]
  • [ 1413920-98-5 ]
  • [ 1413921-03-5 ]
YieldReaction ConditionsOperation in experiment
67% With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In water; toluene for 24h; Inert atmosphere; Reflux; General procedure for 2-(2-isopropoxy-4-nitrophenyl)-5-(4-nitroaryl)furans General procedure: A 2M aqueous solution of Na2CO3 (2.0-2.3 mL) and 4-nitroaryl boronic acid ester 4a-d (1 equiv) in 2-5 mL deaerated methanol or ethanol was added to a stirred solution of 3 (1 equiv) and tetrakistriphenylphosphine palladium (0.05 equiv) in toluene (15-20 mL) under a nitrogen atmosphere. The vigorously stirred mixture was heated to reflux for 24 h. The solvent was evaporated under reduced pressure and hexanes or dioxane were added to the residue. The resulting solid was filtered, washed with hexanes and ether and finally crystallized from either dichloromethane-hexanes or toluene.
  • 7
  • [ 61929-24-6 ]
  • [ 1185019-97-9 ]
  • 2-(2-methoxy-4-nitrophenyl)-1,3,4-thiadiazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
7% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate; In N,N-dimethyl-formamide; at 100℃; for 16h;Inert atmosphere; Prepared in a similar fashion as described in Example 22 except that the following conditions were used in Part B: 2-(2-methoxy-4-nitrophenyl)-4,4,5 ,5 -tetramethyl- 1,3 ,2-dioxaborolane (700 mg, 2.508 mmol), 2-bromo- 1,3 ,4-thiadiazole(414 mg, 2.508 mmol), cesium carbonate (1634 mg, 5.02 mmol), and DMF (12 mL)were combined. N2 was bubbled into the reaction mixture for 2 mi (1,1?-Bis(diphenylphosphino)ferrocene)-dichloropalladium(II) dichloromethane complex(206 mg, 0.25 1 mmol) was then added and the reaction mixture was stirred at 100 Cfor 16 h. The mixture was cooled to room temperature, and was filtered through apad of diatomaceous earth (Celite) with ethyl acetate rinsing. The filtrate was transferred to a separatory funnel containing saturated aqueous NaHCO3 solution (15 mL). The aqueous layer was extracted with ethyl acetate (3 x 15 mL). The combined organic layers were washed with brine (10 mL), dried over MgSO4,filtered, and concentrated. The residue was purified by column chromatography on silica gel (1% -* 3% MeOH in CH2C12) to afford 2-(2-methoxy-4-nitrophenyl)-1,3,4- thiadiazole (42 mg, 7% yield) as a light brown solid: LC/MS (ESI) m/e 238.2 ((M+H), calcd for C9H8N303S 238.0).
  • 8
  • [ 19798-80-2 ]
  • [ 1185019-97-9 ]
  • 4-(2-methoxy-4-nitrophenyl)pyridin-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
63% With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate In butan-1-ol at 100℃; for 4.5h; Inert atmosphere; 45.A Part A. 4-(2-methoxy-4-nitrophenyl)pyridin-2-amine To a mixture of 4-chloropyridin-2-amine (100 mg, 0.778 mmol), K3P04 (413 mg, 1.945 mmol), palladium(II) acetate (17.46 mg, 0.078 mmol), and 2- dicyclohexylphosphino-2’,6’-dimethoxy- 1,1 ‘-biphenyl (63.9 mg, 0.156 mmol) under nitrogen in a vial was added 2-(2-methoxy-4-nitrophenyl)-4,4,5 ,5 -tetramethyl- 1,3,2- dioxaborolane (239 mg, 0.856 mmol), prepared as described in Example 26 Part A, inn-butanol (2 mL). The reaction mixture was heated at 100 °C for 4.5 h. The mixture was cooled to room temperature and was filtered through a pad of diatomaceous earth (Celite) with methanol rinsing and the filtrate was concentrated. The residue was purified by column chromatography on silica gel (1% -* 4% methanol in dichloromethane; 12g column) to afford 4-(2-methoxy-4-nitrophenyl)pyridin-2-amine (120 mg, 63% yield) as a pale yellow solid: ‘H NMR (400MHz, DMSO-d6) ö7.97 (dd, J5.3, 0.8 Hz, 1H), 7.92 (dd, J=8.3, 2.3 Hz, 1H), 7.89 (d, J2.3 Hz, 1H),7.57 (d,J=8.5 Hz, 1H), 6.61 (dd,J5.3, 1.5 Hz, 1H), 6.58 (dd,J1.3, 0.8 Hz, 1H),6.04 (s, 2H), 3.93 (s, 3H); LC/MS (ESI) m/e 246.1 [(M+H), calcd for C,2H,2N303246.1].
63% With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate In butan-1-ol at 100℃; for 4.5h; Inert atmosphere;
  • 9
  • [ 1185019-97-9 ]
  • [ 13526-66-4 ]
  • 6-chloro-3-(2-methoxy-4-nitrophenyl)imidazo[1,2-b]pyridazine [ No CAS ]
YieldReaction ConditionsOperation in experiment
19% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate In water; acetonitrile at 150℃; for 1h; Inert atmosphere; Microwave irradiation; 46.B Part B. 6-Chloro-3 -(2-methoxy-4-nitrophenyl)imidazo [1 ,2-b]pyridazine A mixture of 3-bromo-6-chloroimidazo[1,2-b]pyridazine (200 mg, 0.860mmol), 2-(2-methoxy-4-nitrophenyl)-4,4,5 ,5 -tetramethyl- 1,3 ,2-dioxaborolane (264 mg, 0.946 mmol), prepared according to the procedure described in Example 22 Part A, and sodium carbonate (2 M in H20) (1.291 mL, 2.58 mmol) in acetonitrile (10 mL) was degassed followed by the addition of PdC12(dppf).CH2C12 adduct (70.3 mg,0.086 mmol). The mixture was heated to 150 °C in a microwave for 60 minutes. The mixture was filtered through a pad of diatomaceous earth (Celite) and was concentrated. The residue was purified by reverse phase HPLC (acetonitrile/water with 0.1% TFA) to afford 6-chloro-3-(2-methoxy-4-nitrophenyl)imidazo[ 1,2- b]pyridazine (50 mg, 19% yield) as a yellow solid: LC/MS (ESI) m/e 305.0 [(M+H),calcd for C,3H,0N403C1 305.0].
  • 10
  • [ 1185019-97-9 ]
  • N-benzyl-3-bromo-N-methylimidazo[1,2-b]pyridazin-6-amine [ No CAS ]
  • N-benzyl-3-(2-methoxy-4-nitrophenyl)-N-methylimidazo[1,2-b]pyridazin-6-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
68% With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In tetrahydrofuran at 70℃; for 2h; Microwave irradiation; 49.B Part B. N-Benzyl-3 -(2-methoxy-4-nitrophenyl)-N-methylimidazo [1 ,2-b]pyridazin-6- amine A mixture of N-benzyl-3 -bromo-N-methylimidazo [1 ,2-b]pyridazin-6-amine(120 mg, 0.378 mmol), 2-(2-methoxy-4-nitrophenyl)-4,4,5 ,5 -tetramethyl- 1,3,2-dioxaborolane (116 mg, 0.4 16 mmol), prepared according to the procedure described in Example 22 Part A, and sodium carbonate (2M in H20) (0.567 mL, 1.135 mmol) in THF (5 mL) was degassed. Bis(triphenylphosphene)palladium(II) chloride (13.28 mg, 0.0 19 mmol) was added and the mixture was heated to 70 °C in a microwave for2 h. The reaction mixture was transferred to a separatory funnel containing saturated aqueous NaHCO3 solution (25 mL). The aqueous layer was extracted with ethyl acetate (3 x 25 mL). The combined organic layers were washed with brine (25 mL), dried over MgSO4, filtered, and concentrated. The residue was purified by reverse phase HPLC (acetonitrile:water containing 0.1% TFA) to afford N-benzyl-3-(2-methoxy-4-nitrophenyl)-N-methylimidazo [1 ,2-b]pyridazin-6-amine (100 mg, 68% yield) as a yellow solid: LC/MS (ESI) m/e 390.1 [(M + H), calcd for C2,H20N503 390.2].
  • 11
  • [ 554-84-7 ]
  • [ 1185019-97-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: bromine / acetic acid / 16 h / 125 °C 2.1: lithium hydroxide / tetrahydrofuran / 1 h / 0 °C 2.2: 20 °C 3.1: potassium acetate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 1,4-dioxane / 16 h / 80 °C
  • 12
  • [ 52427-05-1 ]
  • [ 1185019-97-9 ]
  • 13
  • [ 1185019-97-9 ]
  • 3-methoxy-4-(pyridazin-4-yl)aniline [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: caesium carbonate; copper(l) chloride; 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate / N,N-dimethyl-formamide / 16 h / 100 °C / Inert atmosphere 2: palladium 10% on activated carbon; hydrogen / ethanol / 2 h / 2068.65 Torr
Multi-step reaction with 2 steps 1.1: caesium carbonate; copper(l) chloride / N,N-dimethyl-formamide / 0.08 h / Inert atmosphere 1.2: 16 h / 100 °C / Inert atmosphere 2.1: palladium 10% on activated carbon; hydrogen / chloroform; ethanol / 1.5 h / 2068.65 Torr
  • 14
  • [ 1185019-97-9 ]
  • (R)-tert-butyl-1-(3-methoxy-4-(pyridazin-4-yl)phenylamino)-4-methyl-1-oxopentan-2-yl-carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: caesium carbonate; copper(l) chloride; 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate / N,N-dimethyl-formamide / 16 h / 100 °C / Inert atmosphere 2: palladium 10% on activated carbon; hydrogen / ethanol / 2 h / 2068.65 Torr 3: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 16.08 h / 20 - 40 °C
Multi-step reaction with 3 steps 1.1: caesium carbonate; copper(l) chloride / N,N-dimethyl-formamide / 0.08 h / Inert atmosphere 1.2: 16 h / 100 °C / Inert atmosphere 2.1: palladium 10% on activated carbon; hydrogen / chloroform; ethanol / 1.5 h / 2068.65 Torr 3.1: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / dichloromethane / 40 °C / Inert atmosphere
  • 15
  • [ 1185019-97-9 ]
  • (R)-2-amino-N-(3-methoxy-4-(pyridazin-4-yl)phenyl)-4-methylpentanamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: caesium carbonate; copper(l) chloride; 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate / N,N-dimethyl-formamide / 16 h / 100 °C / Inert atmosphere 2: palladium 10% on activated carbon; hydrogen / ethanol / 2 h / 2068.65 Torr 3: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 16.08 h / 20 - 40 °C 4: trifluoroacetic acid / dichloromethane / 1.5 h / 0 - 20 °C / Inert atmosphere
Multi-step reaction with 4 steps 1.1: caesium carbonate; copper(l) chloride / N,N-dimethyl-formamide / 0.08 h / Inert atmosphere 1.2: 16 h / 100 °C / Inert atmosphere 2.1: palladium 10% on activated carbon; hydrogen / chloroform; ethanol / 1.5 h / 2068.65 Torr 3.1: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / dichloromethane / 40 °C / Inert atmosphere 4.1: trifluoroacetic acid / dichloromethane / 2 h / 20 °C / Inert atmosphere
  • 16
  • [ 1185019-97-9 ]
  • 4-(4-amino-2-methoxyphenyl)pyridin-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate / butan-1-ol / 4.5 h / 100 °C / Inert atmosphere 2.1: tin(II) chloride dihdyrate / ethanol / 0.33 h / 70 °C 2.2: 2 h / 20 °C
Multi-step reaction with 2 steps 1.1: dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate / butan-1-ol / 4.5 h / 100 °C / Inert atmosphere 2.1: tin(II) chloride dihdyrate / ethanol / 0.33 h / 70 °C / Inert atmosphere 2.2: 2 h / 20 °C / Inert atmosphere
  • 17
  • [ 1185019-97-9 ]
  • 4-(6-chloroimidazo[1,2-b]pyridazin-3-yl)-3-methoxyaniline [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: sodium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / water; acetonitrile / 1 h / 150 °C / Inert atmosphere; Microwave irradiation 2: tin(II) chloride dihdyrate / ethanol; ethyl acetate / 3 h / 70 °C
  • 18
  • [ 115514-66-4 ]
  • [ 1185019-97-9 ]
  • 4-(2-methoxy-4-nitrophenyl)pyridazine [ No CAS ]
YieldReaction ConditionsOperation in experiment
27% With 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; caesium carbonate; copper(l) chloride In N,N-dimethyl-formamide at 100℃; for 16h; Inert atmosphere; 22.B Part B. 4-(2-Methoxy-4-nitrophenyl)pyridazine 2-(2-methoxy-4-nitrophenyl)-4,4,5 ,5 -tetramethyl- 1,3 ,2-dioxaborolane (750 mg, 2.69 mmol), 4-bromopyridazine (427 mg, 2.69 mmol), cesium carbonate (1751 mg, 5.37 mmol), copper (I) chloride (266 mg, 2.69 mmol) and DMF (18 mL) were combined. N2 was bubbled into the reaction mixture for 5 mm. Dppf (149 mg, 0.269 mmol) and Pd(OAc)2 (30.2 mg, 0.134 mmol) were then added and the reactionmixture was stirred at 100 °C for 16 h. The mixture was cooled to room temperature, and was filtered through a pad of diatomaceous earth (Celite) with ethyl acetate rinsing. The filtrate was transferred to a separatory funnel containing saturated aqueous NaHCO3 solution (25 mL). The aqueous layer was extracted with ethyl acetate (3 x 50 mL). The combined organic layers were washed with brine (25 mL),dried over MgSO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel (1% -* 7% MeOH in CH2C12) to afford 4-(2-methoxy- 4-nitrophenyl)pyridazine (169 mg, 27% yield) as a light brown solid: ‘H NMR (400 MHz, CDC13) ö 9.42 (dd, J=2.3, 1.3 Hz, 1 H), 9.31 (dd, J5.4, 1.1 Hz, 1 H), 8.02 (dd, J8.3, 2.0 Hz, 1 H), 7.92 (d, J2.3 Hz, 1 H), 7.68 (dd, J=5.4, 2.4 Hz, 1 H), 7.56 (d,J8.3 Hz, 1 H), 4.01 (s, 3 H); LC/MS (ESI) m/e 232.1 [(M+H), calcd for C,,H,0N303 232.1].
27% Stage #1: 4-bromopyridazine; 2-(2-methoxy-4-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane With caesium carbonate; copper(l) chloride In N,N-dimethyl-formamide for 0.0833333h; Inert atmosphere; Stage #2: With 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate In N,N-dimethyl-formamide at 100℃; for 16h; Inert atmosphere;
  • 19
  • [ 319906-45-1 ]
  • [ 1185019-97-9 ]
  • C22H20BrNO [ No CAS ]
  • 20
  • [ 319906-45-1 ]
  • [ 1185019-97-9 ]
  • C22H18BrNO3 [ No CAS ]
  • 21
  • [ 1185019-97-9 ]
  • 2-(3,5-dimethylimidazol-4-yl)-5-nitro-phenol [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: potassium carbonate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / methanol; tetrahydrofuran / 0.33 h / 90 °C / Inert atmosphere; Sealed tube 2: boron tribromide / dichloromethane / 4.25 h / 0 - 20 °C / Cooling with ice
  • 22
  • [ 861325-16-8 ]
  • [ 1185019-97-9 ]
  • 5-(2-methoxy-4-nitro-phenyl)-1,4-dimethyl-imidazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
235 mg With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate In tetrahydrofuran; methanol at 90℃; for 0.333333h; Inert atmosphere; Sealed tube; 253 Preparation 253 5-(2-Methoxy-4-nitro-phenyl)-l, 4-dimethyl-imidazole The crude boronic ester (2.59 mmol), 5-bromo-l, 4-dimethyl-imidazole (453 mg, 2.59 mmol), potassium carbonate (715 mg, 5.17 mmol), water (2.6 mL) and Pd(dppf)C (211 mg, 0.26 mmol) were combined in THF (10 mL) and MeOH (0.85 mL) in a 20 mL microwave vial. The vial was flushed with argon for 5 min, capped and stirred for 20 min at 90°C, then allowed to cool to room temperature and diluted with EtOAc (50 mL), washed with water (2 x 10 mL) and brine (10 mL), dried (MgS04), filtered and concentrated in vacuo. The residue was purified by column chromatography (silica, eluting with EtOAc/MeOH) to give the title compound (235 mg, 37%). 1H NMR (600 MHz, DMSO-d6) d 7.91 (dd, J = 8.2, 2.2 Hz, 1H), 7.88 (d, J = 2.2 Hz, 1H), 7.63 (s, 1H), 7.51 (d, J = 8.3 Hz, 1H), 3.92 (s, 3H), 3.41 (s, 3H), 2.00 (s, 3H); LCMS (METHOD 3) (ES) : m/z 248.5 [M + H]+, RT = 0.42 min.
  • 23
  • [ 1185019-97-9 ]
  • 4-bromo-3,5-diethyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole [ No CAS ]
  • 3,5-diethyl-4-(2-methoxy-4-nitrophenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
91% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate In N,N-dimethyl-formamide; mineral oil at 120℃; for 16h; Inert atmosphere; 313 Preparation 292 (1290) (S)-N-(l,l-dicyclopropyl-3-((4-(4-isopropyl-l-((2-(trimethylsilyl)ethoxy)methyl)-lH- imidazol-5-yl)phenyl)amino)-3-oxopropan-2-yl)-l-isopropyl-lH-pyrazole-5-carboxamide and (S)-N-(l,l-dicyclopropyl-3-((4-(5-isopropyl-l-((2-(trimethylsilyl)ethoxy)methyl)-lH- imidazol-4-yl)phenyl)amino)-3-oxopropan-2-yl)-l-isopropyl-lH-pyrazole-5-carboxamide General procedure: To a stirred solution of the boronic ester of Preparation 281 (119 mg, 0.235 mmol) and the bromides of Preparation 287 (50 mg, 0.157 mmol, mixture of isomers) in 1,4-dioxane (5 mL) and H2O (1 ml_), was added Na2CC>3 (50 mg, 0.471 mmol) at room temperature. The resulting reaction mixture was purged with argon for 15 min, Pd(dppf)Cl2.CH2Cl2 was added and the mixture was heated at 120°C for 16 hours. The reaction mixture was filtered through a Celite pad and washed with EtOAc (50 mL). The organic layer was separated, dried over dry Na2SC>4, filtered and concentrated under reduced pressure to give a mixture of the title compounds (50 mg, crude) as a black oil. LCMS (METHOD 5) (ESI) : m/z: 619 [M + H+]; RT = 4.78 min (ACQUITY BEH C18 column, 0.01% FA in water with MeCN).
  • 26
  • [ 1185019-97-9 ]
  • (R)-tert-butyl-(1-((3-methoxy-4-(pyrimidin-4-yl)phenyl)amino)-4-methyl-1-oxopentan-2-yl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: potassium phosphate; XPhos / water; tetrahydrofuran / 16 h / 70 °C / Sonication; Sealed tube; Inert atmosphere 2: ammonium chloride; zinc / ethanol / 1.5 h / 70 °C / Inert atmosphere 3: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / dichloromethane / 16 h / 20 °C / Inert atmosphere
  • 27
  • [ 1185019-97-9 ]
  • C23H32N4O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate / butan-1-ol / 4.5 h / 100 °C / Inert atmosphere 2.1: tin(II) chloride dihdyrate / ethanol / 0.33 h / 70 °C / Inert atmosphere 2.2: 2 h / 20 °C / Inert atmosphere 3.1: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / dichloromethane / 16 h / 20 °C / Inert atmosphere
  • 28
  • [ 1185019-97-9 ]
  • (R)-2-amino-N-(3-methoxy-4-(pyrimidin-4-yl)phenyl)-4-methylpentanamide trifluoroacetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: potassium phosphate; XPhos / water; tetrahydrofuran / 16 h / 70 °C / Sonication; Sealed tube; Inert atmosphere 2: ammonium chloride; zinc / ethanol / 1.5 h / 70 °C / Inert atmosphere 3: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / dichloromethane / 16 h / 20 °C / Inert atmosphere 4: dichloromethane / 2 h / 20 °C / Inert atmosphere
  • 29
  • [ 1185019-97-9 ]
  • (R)-2-amino-N-(4-(2-aminopyridin-4-yl)-3-methoxyphenyl)-4-methylpentanamide trifluoroacetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate / butan-1-ol / 4.5 h / 100 °C / Inert atmosphere 2.1: tin(II) chloride dihdyrate / ethanol / 0.33 h / 70 °C / Inert atmosphere 2.2: 2 h / 20 °C / Inert atmosphere 3.1: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / dichloromethane / 16 h / 20 °C / Inert atmosphere 4.1: dichloromethane / 2 h / 20 °C / Inert atmosphere
  • 30
  • [ 1185019-97-9 ]
  • C22H20BrNO [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; 1,1'-bis-(diphenylphosphino)ferrocene; potassium carbonate / water; 1,4-dioxane / 70 °C 2: tin(II) chloride dihdyrate / ethanol / Reflux
Same Skeleton Products
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