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[ CAS No. 937263-43-9 ] {[proInfo.proName]}

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Chemical Structure| 937263-43-9
Chemical Structure| 937263-43-9
Structure of 937263-43-9 * Storage: {[proInfo.prStorage]}
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Product Details of [ 937263-43-9 ]

CAS No. :937263-43-9 MDL No. :
Formula : C26H24N8O2 Boiling Point : -
Linear Structure Formula :- InChI Key :SDEAXTCZPQIFQM-UHFFFAOYSA-N
M.W : 480.52 Pubchem ID :51039094
Synonyms :

Calculated chemistry of [ 937263-43-9 ]

Physicochemical Properties

Num. heavy atoms : 36
Num. arom. heavy atoms : 25
Fraction Csp3 : 0.19
Num. rotatable bonds : 6
Num. H-bond acceptors : 7.0
Num. H-bond donors : 2.0
Molar Refractivity : 141.66
TPSA : 110.85 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : Yes
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : Yes
CYP2C9 inhibitor : Yes
CYP2D6 inhibitor : Yes
CYP3A4 inhibitor : Yes
Log Kp (skin permeation) : -6.4 cm/s

Lipophilicity

Log Po/w (iLOGP) : 4.14
Log Po/w (XLOGP3) : 3.99
Log Po/w (WLOGP) : 4.52
Log Po/w (MLOGP) : 3.27
Log Po/w (SILICOS-IT) : 3.19
Consensus Log Po/w : 3.82

Druglikeness

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

Water Solubility

Log S (ESOL) : -5.45
Solubility : 0.0017 mg/ml ; 0.00000354 mol/l
Class : Moderately soluble
Log S (Ali) : -6.02
Solubility : 0.000459 mg/ml ; 0.000000956 mol/l
Class : Poorly soluble
Log S (SILICOS-IT) : -9.12
Solubility : 0.000000365 mg/ml ; 0.0000000008 mol/l
Class : Poorly soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 2.0
Synthetic accessibility : 4.01

Safety of [ 937263-43-9 ]

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

Application In Synthesis of [ 937263-43-9 ]

* 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 [ 937263-43-9 ]

[ 937263-43-9 ] Synthesis Path-Downstream   1~26

  • 1
  • [ 64-17-5 ]
  • [ 937263-43-9 ]
  • [ 1429632-07-4 ]
YieldReaction ConditionsOperation in experiment
89% at 65℃; [001 54j Step 3: N4-(4-([ 1 ,2,4]Triazolo [1,5 -a]pyridin-7-yloxy)-3 -methylphenyl)-N6- (4,4-dimethyl-4,5 -dihydrooxazol-2-yl)quinazoline-4,6-diamine from Step 2 was triturated in ethanol at greater than 65°C to provide N4-(4-([ 1 ,2,4]triazolo [1,5 -a]pyridin-7-yloxy)-3 - methylphenyl)-N6-(4,4-dimethyl-4,5 -dihydrooxazol-2-yl)quinazoline-4,6-diamine Form B Ethanol (89%).
  • 2
  • [ 1429755-58-7 ]
  • [ 937263-43-9 ]
YieldReaction ConditionsOperation in experiment
96% With p-toluenesulfonyl chloride; sodium hydroxide In tetrahydrofuran [001 53j Step 2: 1 -(4-((4-([ 1 ,2,4]Triazolo [1,5 -a]pyridin-7-yloxy)-3 -methylphenyl) amino)quinazolin-6-yl)-3-( 1 -hydroxy-2-methylpropan-2-yl)thiourea was agitated in tetrahydrofuran under basic conditions (2.5N NaOH), followed by the addition ofptoluenesulfonyl chloride. Water was charged to yield N4-(4-([ 1 ,2,4]triazolo [1,5 -a]pyridin-7- yloxy)-3 -methylphenyl)-N6-(4,4-dimethyl-4,5 -dihydrooxazol-2-yl)quinazoline-4,6-diamine (96%) as a mixture of polymorphs (generally a mixture containing one or more of Form C,
96% With p-toluenesulfonyl chloride; sodium hydroxide In tetrahydrofuran 12.2 N4-(4-([1,2,4]triazolo[1,5-α]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine freebase hemi-ethanolate Step 2: 1-(4-((4-([1,2,4]Triazolo[1,5-α]pyridin-7-yloxy)-3-methylphenyl)amino)quinazolin-6-yl)-3-(1-hydroxy-2-methylpropan-2-yl)thiourea was agitated in tetrahydrofuran under basic conditions (2.5N NaOH), followed by the addition of p-toluenesulfonyl chloride. Water was charged to yield N4-(4-([1,2,4]triazolo[1,5-α]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine (96%) as a mixture of polymorphs (generally a mixture containing one or more of Form C, Form G hemi-THF, Form G mono-THF, Form M or Form P).
92% With p-toluenesulfonyl chloride; sodium hydroxide In tetrahydrofuran
77% With p-toluenesulfonyl chloride; sodium hydroxide In tetrahydrofuran at 50 - 60℃; for 3h; Tucatinib (1) NaOH powder (12.0 g, 0.30 mol) and p-TsCl (19.1 g, 0.10 mol) were added successivelyto a suspension of compound 14 (25.8 g, 0.05 mol) in THF (400 mL) at room temperatureand the mixture was stirred and heated in an oil bath at 5060 C for 3 h to givea white suspension. The solvents were removed under reduced pressure to obtain a yellowpaste. EtOAc (400 mL) was added to the residue and the resulting solution waswashed with water (300mL 1) and brine (300mL 1) successively. The EtOAc wasremoved under reduced pressure to obtain a yellow foam (29 g), which was mixed withMeOH (40 mL) and heated to reflux for 30 min to give a clear solution, EtOAc (80 mL)was added and the suspension was stirred at 5-10 C for 1 h. The resulting solid wascollected by suction filtration, washed with EtOAc (20mL 2), and dried at 45 C for6 h to give an off-white solid (21 g). It was dissolved in DMF (100 mL) at 80 C. Thehot solution was filtered through a celite pad (20 g), rinsed with DMF (10mL 2).Water (20 mL) was added dropwise to the filtrate and the resulting solution was stirredat 5-10 C for 1 h. The solid obtained was collected by suction filtration, washed withMeOH (10mL 3), and dried at 55 C for 12 h to give 1 (17.8 g, 77%) as a white solid;mp 251.2254.7 C. 1H NMR (400 MHz, DMSO-d6) d 9.58 (s, 1H), 8.94 (d, J7.5 Hz,1H), 8.50 (s, 1H), 8.38 (s, 1H), 8.03 (brs, 1H), 7.92 (s, 1H), 7.87 (d, J8.5 Hz, 1H), 7.67(d, J8.5 Hz, 1H), 7.59-7.41 (m, 1H), 7.20 (d, J8.7 Hz, 1H), 7.03 (dd, J7.5, 2.6 Hz,1H), 6.80 (d, J2.3 Hz, 1H), 4.08 (s, 2H), 2.19 (s, 3H), 1.29 (s, 6H). 13C NMR(100 MHz, DMSO-d6): d 16.3, 27.5, 78.1, 97.9, 107.8, 116.2, 121.6, 121.9, 125.4, 128.5,130.2, 130.8, 137.9, 145.9, 147.7, 151.7, 152.6, 155.1, 157.4, 160.2. MS (ESI): m/z481.2 [MH].HPLC Conditions - Column: Acclaim C18 (150mm 2.1mm 5 mm); Detection:210, 244 nm; Flow rate: 0.8 mL/min; Temperature: 45 C; Injection load: 1 lL; Solvent:methanol; Concentration: 0.2 mg/mL; Run time: 40 min; Mobile phase: methanol (0.1%NH3)/water 70/30, tR: 18.79 min, purity: 99.85%.Anal. Calcd for C26H24N8O2: C, 64.99; H, 5.03; N, 23.32. Found: C, 64.84; H, 5.06;N, 23.25.
With p-toluenesulfonyl chloride; sodium hydroxide In tetrahydrofuran 12.2 1 -(4-((4-([1,2,4]Triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)amino)quinazolin-6-yl)-3-(1-hydroxy-2-methylpropan-2-yl)thiourea was agitated in tetrahydrofuran under basic conditions (2.5N NaOH), followed by the addition of p-toluenesulfonyl chloride. Water was charged to yield N4-(4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine(96%) as a mixture of polymorphs (generally a mixture containing one or more of Form C, Form G hemi-THF, Form G mono-THF, Form M or Form P).
25 % With p-toluenesulfonyl chloride; sodium hydroxide In tetrahydrofuran at 20℃; Tucatinib (N4-(4-([1,2,4]Triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine) (1) The compound was obtained following the reported procedure [1]. To a solution of 14 (0.52 g and 1.01 mmol) in dry THF (10 mL) was added sodium hydroxide (NaOH, 0.19 g and 4.65 mmol), as well as p-toluenesulfonyl chloride (pTsCl, 0.29 g and 1.52 mmol). The reaction mixture was stirred at room temperature for 1 d, and then, quenched by the addition of water. The pH of the solution was then adjusted to pH 7 using 1 M HCl, extracted with EtOAc, dried over sodium sulfate (Na2SO4), filtered, and concentrated under reduced pressure. Purification by flash chromatography (DCM/MeOH, 96/4) yielded 0.12 g (25 %) of 1 as a brown solid. Rf = 0.40 (DCM/MeOH, 9/1); 1H-NMR (600 MHz, DMSO-d6) &120575; 9.68 (s, 1H), 8.93 (d, J = 7.5 Hz, 1H), 8.52 (s, 1H), 8.37 (s, 1H), 8.11 (s, 1H), 7,89 (d, J = 2.6 Hz, 1H), 7.87 - 7,82 (m, 1H), 7.72 - 7.62 (m, 2H), 7.20 (d, J = 8.7 Hz, 1H), 7.02 (dd, J = 7.5, 2.6 Hz, 1H), 6.79 (d, J = 2.6 Hz, 1H), 4.15 (s, 2H), 2.19 (s, 3H), 1.30 (s, 6H); 13C-NMR (151 MHz, DMSO-d6) &120575; 159.66, 157.08, 155.74, 154.60, 152.37, 151.18, 147.39, 145.30, 143.72, 137.18, 130.39, 129.82, 128.02, 127.87, 125.13, 121.57, 121.20, 115.62, 113.61, 107.35, 97.51, 78.16, 58.11, 26.83, 15.83; MS (ESI), m/z calcd for C26H25N8O2+ [M+H]+ 481.21, found 481.2.
25 % With p-toluenesulfonyl chloride; sodium hydroxide In tetrahydrofuran at 20℃; Tucatinib (N4-(4-([1,2,4]Triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine) (1) The compound was obtained following the reported procedure [1]. To a solution of 14 (0.52 g and 1.01 mmol) in dry THF (10 mL) was added sodium hydroxide (NaOH, 0.19 g and 4.65 mmol), as well as p-toluenesulfonyl chloride (pTsCl, 0.29 g and 1.52 mmol). The reaction mixture was stirred at room temperature for 1 d, and then, quenched by the addition of water. The pH of the solution was then adjusted to pH 7 using 1 M HCl, extracted with EtOAc, dried over sodium sulfate (Na2SO4), filtered, and concentrated under reduced pressure. Purification by flash chromatography (DCM/MeOH, 96/4) yielded 0.12 g (25 %) of 1 as a brown solid. Rf = 0.40 (DCM/MeOH, 9/1); 1H-NMR (600 MHz, DMSO-d6) &120575; 9.68 (s, 1H), 8.93 (d, J = 7.5 Hz, 1H), 8.52 (s, 1H), 8.37 (s, 1H), 8.11 (s, 1H), 7,89 (d, J = 2.6 Hz, 1H), 7.87 - 7,82 (m, 1H), 7.72 - 7.62 (m, 2H), 7.20 (d, J = 8.7 Hz, 1H), 7.02 (dd, J = 7.5, 2.6 Hz, 1H), 6.79 (d, J = 2.6 Hz, 1H), 4.15 (s, 2H), 2.19 (s, 3H), 1.30 (s, 6H); 13C-NMR (151 MHz, DMSO-d6) &120575; 159.66, 157.08, 155.74, 154.60, 152.37, 151.18, 147.39, 145.30, 143.72, 137.18, 130.39, 129.82, 128.02, 127.87, 125.13, 121.57, 121.20, 115.62, 113.61, 107.35, 97.51, 78.16, 58.11, 26.83, 15.83; MS (ESI), m/z calcd for C26H25N8O2+ [M+H]+ 481.21, found 481.2.
With p-toluenesulfonyl chloride; sodium hydroxide In N,N-dimethyl-formamide at 60℃; 3 Scheme 1: Prepare a three-necked flask, set up a thermometer, add intermediate compounds to it, then add DMF, stir and dissolve the mixed reaction solution, add sodium hydroxide and p-toluenesulfonyl chloride, heat the mixed reaction solution to 60°C, and react for 3 hours.The reaction solution was poured into stirred water, stirred thoroughly for 2 hours, and a solid precipitated out, which was filtered.The solid was recrystallized from methanol to give a white solid.Detect HPLC content≥98%.

  • 3
  • [ 99-53-6 ]
  • [ 937263-43-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1.1: N-ethyl-N,N-diisopropylamine / 1-methyl-pyrrolidin-2-one / 24 h / 150 °C 2.1: N,N-dimethyl acetamide / 6 h / 75 °C 2.2: 3 h / 40 - 50 °C 3.1: trifluoroacetic anhydride; calcium(II) chloride / tetrahydrofuran / 5 h / 5 - 25 °C / Cooling with ice 4.1: 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 15 h / 40 °C 5.1: glacial acetic acid / 2 h / 85 °C 6.1: palladium on activated charcoal / tetrahydrofuran / 5 h / 20 °C 7.1: Cs2CO3 / N,N-dimethyl-formamide / 1 h / 20 °C 7.2: 20 h / 125 °C / Sealed tube
Multi-step reaction with 8 steps 1.1: N-ethyl-N,N-diisopropylamine / 1-methyl-pyrrolidin-2-one / 48 h / 150 °C 2.1: ethanol / 3 h / 75 °C 3.1: hydroxyamino hydrochloride / ethanol / 3 h / 50 °C 4.1: trifluoroacetic anhydride / tetrahydrofuran / 5 - 25 °C 5.1: 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 15 h / 40 °C 6.1: glacial acetic acid / 2 h / 85 °C 7.1: 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 5 h / 20 °C 8.1: Cs2CO3 / N,N-dimethyl-formamide / 20 °C 8.2: 20 h / 125 °C
Multi-step reaction with 8 steps 1.1: N-ethyl-N,N-diisopropylamine / 1-methyl-pyrrolidin-2-one / 48 h / 150 °C 2.1: ethanol / 3 h / 75 °C 3.1: hydroxyamino hydrochloride / ethanol / 3 h / 50 °C 4.1: trifluoroacetic anhydride / tetrahydrofuran / 5 - 25 °C 5.1: 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 15 h / 40 °C 6.2: 2 h / 85 °C 7.1: 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 5 h / 20 °C 8.1: Cs2CO3 / N,N-dimethyl-formamide / 20 °C 8.2: 20 h / 125 °C
Multi-step reaction with 4 steps 1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 100 °C 2: palladium on activated charcoal; methanol; hydrogen / 1 h / 20 - 30 °C 3: potassium carbonate / N,N-dimethyl-formamide / 1 h / 80 °C 4: palladium (II) 2,4-pentanedionate; potassium phosphate tribasic trihydrate; 2-(2,6-diethyl-4-methylphenyl)-5-(2,4,6-triisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride / 1,4-dioxane / 24 h / 90 °C / Inert atmosphere

  • 4
  • [ 65370-42-5 ]
  • [ 937263-43-9 ]
  • 5
  • [ 864244-98-4 ]
  • [ 937263-43-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: N,N-dimethyl acetamide / 6 h / 75 °C 1.2: 3 h / 40 - 50 °C 2.1: trifluoroacetic anhydride; calcium chloride / tetrahydrofuran / 5 h / 5 - 25 °C / Cooling with ice 3.1: 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 15 h / 40 °C 4.1: acetic acid / 2 h / 85 °C 5.1: palladium on activated charcoal / tetrahydrofuran / 5 h / 20 °C 6.1: caesium carbonate / N,N-dimethyl-formamide / 1 h / 20 °C 6.2: 20 h / 125 °C / Sealed tube
Multi-step reaction with 7 steps 1.1: ethanol / 3 h / 75 °C 2.1: hydroxylamine hydrochloride / ethanol / 3 h / 50 °C 3.1: trifluoroacetic anhydride / tetrahydrofuran / 5 - 25 °C 4.1: 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 15 h / 40 °C 5.2: 2 h / 85 °C 6.1: 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 5 h / 20 °C 7.1: caesium carbonate / N,N-dimethyl-formamide / 20 °C 7.2: 20 h / 125 °C
Multi-step reaction with 7 steps 1.1: ethanol / 3 h / 75 °C 2.1: hydroxylamine hydrochloride / ethanol / 3 h / 50 °C 3.1: trifluoroacetic anhydride / tetrahydrofuran / 5 - 25 °C 4.1: 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 15 h / 40 °C 5.1: acetic acid / 2 h / 85 °C 6.1: 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 5 h / 20 °C 7.1: caesium carbonate / N,N-dimethyl-formamide / 20 °C 7.2: 20 h / 125 °C
  • 6
  • [ 2307628-65-3 ]
  • [ 937263-43-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: trifluoroacetic anhydride; calcium chloride / tetrahydrofuran / 5 h / 5 - 25 °C / Cooling with ice 2.1: 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 15 h / 40 °C 3.1: acetic acid / 2 h / 85 °C 4.1: palladium on activated charcoal / tetrahydrofuran / 5 h / 20 °C 5.1: caesium carbonate / N,N-dimethyl-formamide / 1 h / 20 °C 5.2: 20 h / 125 °C / Sealed tube
Multi-step reaction with 5 steps 1.1: trifluoroacetic anhydride / tetrahydrofuran / 5 - 25 °C 2.1: 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 15 h / 40 °C 3.2: 2 h / 85 °C 4.1: 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 5 h / 20 °C 5.1: caesium carbonate / N,N-dimethyl-formamide / 20 °C 5.2: 20 h / 125 °C
Multi-step reaction with 5 steps 1.1: trifluoroacetic anhydride / tetrahydrofuran / 5 - 25 °C 2.1: 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 15 h / 40 °C 3.1: acetic acid / 2 h / 85 °C 4.1: 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 5 h / 20 °C 5.1: caesium carbonate / N,N-dimethyl-formamide / 20 °C 5.2: 20 h / 125 °C
  • 7
  • [ 937263-44-0 ]
  • [ 937263-43-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 15 h / 40 °C 2.1: glacial acetic acid / 2 h / 85 °C 3.1: palladium on activated charcoal / tetrahydrofuran / 5 h / 20 °C 4.1: Cs2CO3 / N,N-dimethyl-formamide / 1 h / 20 °C 4.2: 20 h / 125 °C / Sealed tube
Multi-step reaction with 3 steps 1: 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 45 °C 2: glacial acetic acid / Isopropyl acetate / 45 °C 3: p-toluenesulfonyl chloride; sodium hydroxide / tetrahydrofuran
Multi-step reaction with 4 steps 1.1: 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 15 h / 40 °C 2.1: glacial acetic acid / 2 h / 85 °C 3.1: 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 5 h / 20 °C 4.1: Cs2CO3 / N,N-dimethyl-formamide / 20 °C 4.2: 20 h / 125 °C
Multi-step reaction with 4 steps 1.1: 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 15 h / 40 °C 2.2: 2 h / 85 °C 3.1: 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 5 h / 20 °C 4.1: Cs2CO3 / N,N-dimethyl-formamide / 20 °C 4.2: 20 h / 125 °C
Multi-step reaction with 3 steps 1: palladium on activated charcoal; methanol; hydrogen / 1 h / 20 - 30 °C 2: potassium carbonate / N,N-dimethyl-formamide / 1 h / 80 °C 3: palladium (II) 2,4-pentanedionate; potassium phosphate tribasic trihydrate; 2-(2,6-diethyl-4-methylphenyl)-5-(2,4,6-triisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride / 1,4-dioxane / 24 h / 90 °C / Inert atmosphere

  • 8
  • [ 2307628-66-4 ]
  • [ 937263-43-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: palladium on activated charcoal / tetrahydrofuran / 5 h / 20 °C 2.1: caesium carbonate / N,N-dimethyl-formamide / 1 h / 20 °C 2.2: 20 h / 125 °C / Sealed tube
Multi-step reaction with 2 steps 1.1: 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 5 h / 20 °C 2.1: caesium carbonate / N,N-dimethyl-formamide / 20 °C 2.2: 20 h / 125 °C
Multi-step reaction with 3 steps 1.1: hydrogen; 5%-palladium/activated carbon / tetrahydrofuran / 3 h / 30 - 40 °C 2.1: N,N-dimethyl-formamide / 2 h / 5 - 10 °C 2.2: 2 h / 20 °C 3.1: sodium hydroxide; p-toluenesulfonyl chloride / tetrahydrofuran / 3 h / 50 - 60 °C
  • 9
  • [ 1384956-50-6 ]
  • [ 2307628-67-5 ]
  • [ 937263-43-9 ]
YieldReaction ConditionsOperation in experiment
76% Stage #1: 4,4-dimethyl-2-(methylthio)-4,5-dihydrooxazole trifluoromethanesulfonate With caesium carbonate In N,N-dimethyl-formamide at 20℃; Stage #2: N4-(4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)quinazoline-4,6-diamine In N,N-dimethyl-formamide at 125℃; for 20h; Tucatinib (1) Cs2CO3 (26.5 g, 0.082 mol) was added in portions to a suspension of 17 (16.2 g, 0.055 mol) in DMF (70 g) at r.t. and the solution was stirred for 1 h. Compound 15 (16.9 g, 0.044 mol) was added to the reactant and the resulting mixture was stirred at 125 °C for 20 h. The reaction solution was cooled to r.t. and poured into ice H2O (300 g), then stirred at r.t. for 1 h. The resulting solid was collected by suction filtration, washed with H2O (2 * 20 g), and dried at 45 °C for 6 h to give a light-yellow solid (21 g). The crude product and active charcoal (4 g) were suspended in EtOAc (80 g) and heated to reflux for 1 h. The solids were removed by hot filtration and the filtrate was concentrated to around 50 g. Heptane (40 g) was added slowly to the warm solution and the mixture was stirred at r.t. for 12 h. The resulting solid was collected by suction filtration, washed with heptane (2 * 15 g), and dried at 45 °C for 12 h to give 1 (16.1 g, 76%) as a white solid;3 mp 251.2-254.7 °C. 1H NMR (400 MHz, DMSO-d6): δ = 9.58 (s, 1 H), 8.94 (d, J = 7.5 Hz, 1 H), 8.50 (s, 1 H), 8.38 (s, 1 H), 8.03 (br. s, 1 H), 7.92 (s, 1 H), 7.87 (d, J = 8.5 Hz, 1 H), 7.67 (d, J = 8.5 Hz, 1 H), 7.59-7.41 (m, 1 H), 7.20 (d, J = 8.7 Hz, 1 H), 7.03 (dd, J = 7.5, 2.6 Hz, 1 H), 6.80 (d, J = 2.3 Hz, 1 H), 4.08 (s, 2 H), 2.19 (s, 3 H), 1.29 (s, 6 H). 13C NMR (100 MHz, DMSO-d6): δ = 16.3, 27.5, 78.1, 97.9, 107.8, 116.2, 121.6, 121.9, 125.4, 128.5, 130.2, 130.8, 137.9, 145.9, 147.7, 151.7, 152.6, 155.1, 157.4, 160.2. MS (ESI): m/z = 481.2 [M + H]+. Anal. Calcd for C26H24N8O2: C, 64.99; H, 5.03; N, 23.32. Found: C, 64.84; H, 5.06; N, 23.25. HPLC Conditions: Agilent Eclipse XDB-C18 (250 mm * 4.6 mm * 5 µm); Detection: 254 nm; Flow rate: 1.0 mL/min; Temperature: 35 °C; Injection load: 1 µL; Solvent: MeOH; Concentration: 0.5 mg/mL; Run time: 40 min; Mobile phase: MeOH/H2O = 70:30; tR: 7.563 min, purity: 99.9%.
70% Stage #1: 4,4-dimethyl-2-(methylthio)-4,5-dihydrooxazole trifluoromethanesulfonate With caesium carbonate In N,N-dimethyl-formamide at 20℃; for 1h; Stage #2: N4-(4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)quinazoline-4,6-diamine In N,N-dimethyl-formamide at 125℃; for 20h; Sealed tube; 7 Example 7 Preparation of Compound 20 (1) Compound 19 (0.62 g, 2.1 mmol) was dissolved in DMF (4 mL)Add Cs2CO3 (0.68g,2.1mmoL) was stirred at room temperature for 1 h and the solution was transferred to a sealed tube. Compound 16 (0.2 g, 0.52 mmol) was added to the reaction flask.The reaction was stirred at 125 ° C for 20 hours, and the reaction was followed by thin layer chromatography (TLC). After 20 hours, TLC showed the reaction was completed and the reaction solution was poured. In water, stirred, filtered, and recrystallized to give 175 mg of Compound 20 (yield 70%).
  • 10
  • [ 17420-30-3 ]
  • [ 937263-43-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: N,N-dimethyl acetamide / 5 h / 75 °C 2.1: acetic acid / 2 h / 85 °C 3.1: Pd/C / tetrahydrofuran / 5 h / 20 °C 4.1: caesium carbonate / N,N-dimethyl-formamide / 1 h / 20 °C 4.2: 20 h / 125 °C / Sealed tube
Multi-step reaction with 5 steps 1: methanol; tert-butyl methyl ether / 40 °C 2: hydrogen; 10% Pd/C / tetrahydrofuran / 35 °C 3: tetrahydrofuran / -14 °C 4: acetic acid / Isopropyl acetate / 45 °C 5: p-toluenesulfonyl chloride; sodium hydroxide / tetrahydrofuran
Multi-step reaction with 5 steps 1.1: 90 min / 90 °C 2.1: 10% Pd/C; hydrogen / methanol / 5 h / 35 °C 3.1: tetrahydrofuran / 40 min / -5 °C / Sealed tube; Inert atmosphere 3.2: 90 min / 20 °C / Inert atmosphere 4.1: acetic acid / ethyl acetate / 40 °C 5.1: sodium hydroxide; p-toluenesulfonyl chloride / tetrahydrofuran / 1 d / 20 °C
  • 11
  • [ 39263-34-8 ]
  • [ 937263-43-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: acetic acid / 2 h / 85 °C 2.1: Pd/C / tetrahydrofuran / 5 h / 20 °C 3.1: caesium carbonate / N,N-dimethyl-formamide / 1 h / 20 °C 3.2: 20 h / 125 °C / Sealed tube
Multi-step reaction with 4 steps 1.1: 10% Pd/C; hydrogen / methanol / 5 h / 35 °C 2.1: tetrahydrofuran / 40 min / -5 °C / Sealed tube; Inert atmosphere 2.2: 90 min / 20 °C / Inert atmosphere 3.1: acetic acid / ethyl acetate / 40 °C 4.1: sodium hydroxide; p-toluenesulfonyl chloride / tetrahydrofuran / 1 d / 20 °C
  • 12
  • [ 937263-71-3 ]
  • [ 937263-43-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: acetic acid / 2 h / 85 °C 2.1: palladium on activated charcoal / tetrahydrofuran / 5 h / 20 °C 3.1: caesium carbonate / N,N-dimethyl-formamide / 1 h / 20 °C 3.2: 20 h / 125 °C / Sealed tube
Multi-step reaction with 3 steps 1.1: acetic acid / 2 h / 85 °C 2.1: 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 5 h / 20 °C 3.1: caesium carbonate / N,N-dimethyl-formamide / 20 °C 3.2: 20 h / 125 °C
Multi-step reaction with 3 steps 1.2: 2 h / 85 °C 2.1: 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 5 h / 20 °C 3.1: caesium carbonate / N,N-dimethyl-formamide / 20 °C 3.2: 20 h / 125 °C
Multi-step reaction with 4 steps 1.1: acetic acid / ethyl acetate / 4.5 h / 20 - 70 °C 2.1: hydrogen; 5%-palladium/activated carbon / tetrahydrofuran / 3 h / 30 - 40 °C 3.1: N,N-dimethyl-formamide / 2 h / 5 - 10 °C 3.2: 2 h / 20 °C 4.1: sodium hydroxide; p-toluenesulfonyl chloride / tetrahydrofuran / 3 h / 50 - 60 °C

  • 13
  • [ 2887612-93-1 ]
  • [ 937263-43-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: potassium carbonate / N,N-dimethyl-formamide / 83 °C 2: 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 45 °C 3: acetic acid / Isopropyl acetate / 45 °C 4: p-toluenesulfonyl chloride; sodium hydroxide / tetrahydrofuran
  • 14
  • [ 1203904-18-0 ]
  • [ 937263-43-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: hydrogen; 10% Pd/C / tetrahydrofuran / 35 °C 2: tetrahydrofuran / -14 °C 3: acetic acid / Isopropyl acetate / 45 °C 4: p-toluenesulfonyl chloride; sodium hydroxide / tetrahydrofuran
  • 15
  • [ 2131230-48-1 ]
  • [ 937263-43-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: tetrahydrofuran / -14 °C 2: acetic acid / Isopropyl acetate / 45 °C 3: p-toluenesulfonyl chloride; sodium hydroxide / tetrahydrofuran
  • 16
  • [ 2839844-25-4 ]
  • [ 937263-43-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: trifluoroacetic anhydride / dichloromethane / Reflux 2: potassium carbonate / N,N-dimethyl-formamide / 83 °C 3: 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 45 °C 4: acetic acid / Isopropyl acetate / 45 °C 5: p-toluenesulfonyl chloride; sodium hydroxide / tetrahydrofuran
  • 17
  • [ 19798-80-2 ]
  • [ 937263-43-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 8 steps 1.1: N-ethyl-N,N-diisopropylamine / 1-methyl-pyrrolidin-2-one / 48 h / 150 °C 2.1: ethanol / 3 h / 75 °C 3.1: hydroxylamine hydrochloride / ethanol / 3 h / 50 °C 4.1: trifluoroacetic anhydride / tetrahydrofuran / 5 - 25 °C 5.1: 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 15 h / 40 °C 6.1: acetic acid / 2 h / 85 °C 7.1: 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 5 h / 20 °C 8.1: caesium carbonate / N,N-dimethyl-formamide / 20 °C 8.2: 20 h / 125 °C
Multi-step reaction with 8 steps 1.1: N-ethyl-N,N-diisopropylamine / 1-methyl-pyrrolidin-2-one / 48 h / 150 °C 2.1: ethanol / 3 h / 75 °C 3.1: hydroxylamine hydrochloride / ethanol / 3 h / 50 °C 4.1: trifluoroacetic anhydride / tetrahydrofuran / 5 - 25 °C 5.1: 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 15 h / 40 °C 6.2: 2 h / 85 °C 7.1: 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 5 h / 20 °C 8.1: caesium carbonate / N,N-dimethyl-formamide / 20 °C 8.2: 20 h / 125 °C
Multi-step reaction with 7 steps 1.1: ethanol / 2.5 h / 20 - 70 °C 1.2: 2 h / 40 - 55 °C 2.1: trifluoroacetic anhydride / tetrahydrofuran / 1.33 h / 70 °C / Inert atmosphere 3.1: potassium carbonate / N,N-dimethyl-formamide / 17 h / 20 - 140 °C 4.1: acetic acid / ethyl acetate / 4.5 h / 20 - 70 °C 5.1: hydrogen; 5%-palladium/activated carbon / tetrahydrofuran / 3 h / 30 - 40 °C 6.1: N,N-dimethyl-formamide / 2 h / 5 - 10 °C 6.2: 2 h / 20 °C 7.1: sodium hydroxide; p-toluenesulfonyl chloride / tetrahydrofuran / 3 h / 50 - 60 °C
  • 18
  • [ 2543990-16-3 ]
  • [ 937263-43-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: hydroxylamine hydrochloride / ethanol / 3 h / 50 °C 2.1: trifluoroacetic anhydride / tetrahydrofuran / 5 - 25 °C 3.1: 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 15 h / 40 °C 4.2: 2 h / 85 °C 5.1: 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 5 h / 20 °C 6.1: caesium carbonate / N,N-dimethyl-formamide / 20 °C 6.2: 20 h / 125 °C
Multi-step reaction with 6 steps 1.1: hydroxylamine hydrochloride / ethanol / 3 h / 50 °C 2.1: trifluoroacetic anhydride / tetrahydrofuran / 5 - 25 °C 3.1: 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 15 h / 40 °C 4.1: acetic acid / 2 h / 85 °C 5.1: 5%-palladium/activated carbon; hydrogen / tetrahydrofuran / 5 h / 20 °C 6.1: caesium carbonate / N,N-dimethyl-formamide / 20 °C 6.2: 20 h / 125 °C
  • 19
  • [ 937263-71-3 ]
  • 4-hydroxy-6-(4,4-dimethyl-4,5-dihydrooxazol-2-amino)quinazoline [ No CAS ]
  • [ 937263-43-9 ]
YieldReaction ConditionsOperation in experiment
78.2% Stage #1: 4-hydroxy-6-(4,4-dimethyl-4,5-dihydrooxazol-2-amino)quinazoline With dmap; (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate In acetonitrile at 20℃; for 0.5h; Green chemistry; Stage #2: 4-([1,2,4]triazolo[1,5-α]pyridin-7-yloxy)-3-methylaniline In acetonitrile at 20℃; for 18h; Green chemistry; 1-4; 1 4-hydroxy-6-(4,4-dimethyl-4,5-dihydrooxazol-2-amino)quinazoline 0.05moland Carter condensing agentDissolve0.06mol ofBOPin 200ml ofacetonitrile, add0.075mol ofN,N-dimethylaminopyridine, and stir and react at room temperature for 0.5 hours. Then add 4-([1,2,4]triazolo[1,5-a]pyridine-7-oxy)-3-methylaniline 0.06mol,stir at room temperature and react for 18 hoursTime.Concentrate under reduced pressure, add ethyl acetate and water, separate the layers, and use saturated ammonium chloride aqueous solution and sodium bicarbonate aqueous solution in order for the organic phaseWash with brine, dry with anhydrous sodium sulfate, concentrate under reduced pressure to remove the solvent, and recrystallize the residue with water to obtain a white solid product.The yield is 78.2%,HPLC99%.
  • 20
  • [ 2379814-46-5 ]
  • [ 937263-43-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: trifluoroacetic anhydride / tetrahydrofuran / 1.33 h / 70 °C / Inert atmosphere 2.1: potassium carbonate / N,N-dimethyl-formamide / 17 h / 20 - 140 °C 3.1: acetic acid / ethyl acetate / 4.5 h / 20 - 70 °C 4.1: hydrogen; 5%-palladium/activated carbon / tetrahydrofuran / 3 h / 30 - 40 °C 5.1: N,N-dimethyl-formamide / 2 h / 5 - 10 °C 5.2: 2 h / 20 °C 6.1: sodium hydroxide; p-toluenesulfonyl chloride / tetrahydrofuran / 3 h / 50 - 60 °C
  • 21
  • [ 1427452-48-9 ]
  • [ 937263-43-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 17 h / 20 - 140 °C 2.1: glacial acetic acid / ethyl acetate / 4.5 h / 20 - 70 °C 3.1: hydrogen; 5%-palladium/activated carbon / tetrahydrofuran / 3 h / 30 - 40 °C 4.1: N,N-dimethyl-formamide / 2 h / 5 - 10 °C 4.2: 2 h / 20 °C 5.1: sodium hydroxide; p-toluenesulfonyl chloride / tetrahydrofuran / 3 h / 50 - 60 °C
Multi-step reaction with 4 steps 1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 100 °C 2: palladium on activated charcoal; methanol; hydrogen / 1 h / 20 - 30 °C 3: potassium carbonate / N,N-dimethyl-formamide / 1 h / 80 °C 4: palladium (II) 2,4-pentanedionate; potassium phosphate tribasic trihydrate; 2-(2,6-diethyl-4-methylphenyl)-5-(2,4,6-triisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride / 1,4-dioxane / 24 h / 90 °C / Inert atmosphere
  • 22
  • [ 2307628-66-4 ]
  • [ 52832-91-4 ]
  • [ 937263-43-9 ]
YieldReaction ConditionsOperation in experiment
91.8% With potassium phosphate tribasic trihydrate; 2-(2,6-diethyl-4-methylphenyl)-5-(2,4,6-triisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride; palladium (II) 2,4-pentanedionate In 1,4-dioxane at 90℃; for 24h; Inert atmosphere; 10-13 Synthesis of the compound tucatinib shown in Example 10 of formula I To the compound shown in formula 6 (41.34g, 100mmol) and dioxane (410ml) stirred mixture, successively added compound shown in formula 7 (13.70g, 120mmol),K3PO4·3H2O(39.35g, 150mmol), Pd (acac)2(1.52g, 5mmol) and ligand L (compound shown in Formula 8) (5.06g, 10mmol), the reaction liquid is replaced byN2at room temperature, under vacuum After several times, the temperature was heated to 90 °C reaction for 24h, after the reaction was completed, the cooling was treated, the reaction solution was concentrated at low temperature to remove half of the solvent and poured into water (400mL), the precipitated solids were filtered and collected, and the mixed solvent consisting of petroleum ether /ethyl acetate with a volume ratio of 1:1 (200mL) was stirred and purified for 30min, and the solid was obtained after filtering and drying to obtain a solid 44.1g, which was the compound tucatanib shown in formula I, with a yield of 91.8% and a HPLC purity of 99.7%.
  • 23
  • [ 937263-71-3 ]
  • C13H13ClN4O [ No CAS ]
  • [ 937263-43-9 ]
YieldReaction ConditionsOperation in experiment
77.5% With potassium carbonate In N,N-dimethyl-formamide at 20 - 80℃; for 1h; 10-13 Example 10 Synthesis of compound tucatinib shown in formula I At room temperature, the compound shown in formula 3 (24.03g, 100mmol) and K2CO3 (15.48g, 112mmol) were added to the stirring DMF (240mL) and mixed, and then the compound shown in formula 8 (29.33g, 106mmol) was slowly added dropwise. A mixture of DMF (100 mL) and DMF (100 mL) was heated to 80 °C and stirred for 1 h. After the reaction was completed, the reaction solution was poured into water (300 mL). The mixed solvent (280 mL) composed of ethyl acetate was stirred and slurried for 30 min, and the solid was filtered and dried to obtain the compound represented by formula I. The yield was 37.24 g, the yield was 77.5%, and the HPLC purity was 99.8%.
  • 24
  • [ 208533-37-3 ]
  • [ 937263-43-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: dichloromethane / 2 h / -5 - 20 °C / Inert atmosphere 2.1: tetrahydrofuran / 2 h / -5 - 20 °C 2.2: 3 h / -5 - 20 °C 3.1: potassium carbonate / N,N-dimethyl-formamide / 1 h / 20 - 80 °C
  • 25
  • [ 937263-43-9 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1.1: hydroxylamine-O-sulfonic acid; pyridine / methanol / 5 h / 80 °C 2.1: pyridine hydrochloride / 4 h / 170 °C 3.1: N-ethyl-N,N-diisopropylamine / 1-methyl-pyrrolidin-2-one / 1 h / 150 °C / Microwave irradiation; Sealed tube 4.1: iron; hydrogenchloride / methanol / 4 h / 55 °C 5.1: acetic acid / ethyl acetate / 2 d / 40 °C 6.1: sodium hydroxide; p-toluenesulfonyl chloride / tetrahydrofuran / 4 d / 20 °C 7.1: palladium diacetate; 1,3,5,7-tetramethyl-6-phenyl-2,4,8-trioxa-6-phosphaadamantane / 1,4-dioxane / 1 d / 100 °C / Microwave irradiation; Sealed tube; Inert atmosphere 7.2: 1 d / 80 °C / Microwave irradiation; Sealed tube; Inert atmosphere
Multi-step reaction with 7 steps 1: hydroxylamine-O-sulfonic acid; pyridine / methanol / 5 h / 80 °C 2: pyridine hydrochloride / 4 h / 170 °C 3: caesium carbonate / 1-methyl-pyrrolidin-2-one / 20 min / 120 °C 4: iron; hydrogenchloride / methanol / 4 h / 60 °C 5: acetic acid / ethyl acetate / 40 °C 6: sodium hydroxide; p-toluenesulfonyl chloride / tetrahydrofuran / 3 d / 20 °C 7: palladium diacetate; 1,3,5,7-tetramethyl-6-phenyl-2,4,8-trioxa-6-phosphaadamantane / 1,4-dioxane / 135 min / 80 °C / Microwave irradiation; Sealed tube; Inert atmosphere
  • 26
  • [ 937263-43-9 ]
  • [ 1250443-32-3 ]
YieldReaction ConditionsOperation in experiment
37 % With pyridine; hydroxylamine-O-sulfonic acid In methanol at 80℃; 7-Methoxy-[1,2,4]triazolo[1,5-a]pyridine (4) The compound was obtained following the reported procedure [2]. To a solution of 1 (3.61 g and 20.14 mmol) and Hydroxylamine-O-sulfonic acid (HSA, 2.96 g and 26.18 mmol) in MeOH (50 ml) was added Pyridine (3.24 mL and 40.28 mmol). The reaction mixture was stirred at 80 °C under reflux for 5 h, and then allowed to cool down, and concentrated under reduced pressure. The resulting residue was purified by flash chromatography (DCM/MeOH, 99/1) to yield 1.10 g (37 %) of 4 as a light brown solid. Rf = 0.43 (DCM/MeOH, 95/5); 1H-NMR (400 MHz, CDCl3) δ 8.38 (d, J = 7.4 Hz, 1H), 8.21 (s, 1H), 7.01 (d, J = 2.6 Hz, 1H), 6.70 (dd, J = 7.5, 2.6 Hz, 1H), 3.91 (s, 3H); 13C-NMR (101 MHz, CDCl3) δ 161.42, 154.17, 152.09, 128.64, 108.57, 94.46, 56.13; MS (ESI), m/z calcd for C7H8N3O+ [M+H]+ 150.06, found 150.2.
37 % With pyridine; hydroxylamine-O-sulfonic acid In methanol at 80℃; 7-Methoxy-[1,2,4]triazolo[1,5-a]pyridine (4) The compound was obtained following the reported procedure [2]. To a solution of 1 (3.61 g and 20.14 mmol) and Hydroxylamine-O-sulfonic acid (HSA, 2.96 g and 26.18 mmol) in MeOH (50 ml) was added Pyridine (3.24 mL and 40.28 mmol). The reaction mixture was stirred at 80 °C under reflux for 5 h, and then allowed to cool down, and concentrated under reduced pressure. The resulting residue was purified by flash chromatography (DCM/MeOH, 99/1) to yield 1.10 g (37 %) of 4 as a light brown solid. Rf = 0.43 (DCM/MeOH, 95/5); 1H-NMR (400 MHz, CDCl3) δ 8.38 (d, J = 7.4 Hz, 1H), 8.21 (s, 1H), 7.01 (d, J = 2.6 Hz, 1H), 6.70 (dd, J = 7.5, 2.6 Hz, 1H), 3.91 (s, 3H); 13C-NMR (101 MHz, CDCl3) δ 161.42, 154.17, 152.09, 128.64, 108.57, 94.46, 56.13; MS (ESI), m/z calcd for C7H8N3O+ [M+H]+ 150.06, found 150.2.
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