Structure of 6165-68-0
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Pieterse, Lianie ; Beteck, Richard M. ; Baratte, Blandine ; Jesumoroti, Omobolanle J. ; Robert, Thomas ; Ruchaud, Sandrine , et al.
Abstract: Protein kinases, including CDK9/CyclinT and Haspin, are regarded as potential drug targets in cancer therapy. Findings from a previous study suggested 7-azaindole as a privileged scaffold for producing inhibitors of CDK9/CyclinT and Haspin. Inspired by these findings, the current study synthesized and evaluated thirteen (13) C6-substituted 7-azaindole and twenty (20) C4-substituted structurally related 7H-pyrrolo[2,3-d]pyrimidine derivatives against a panel of protein kinases, including CDK9/CyclinT and Haspin. Eleven of the 7H-pyrrolo[2,3-d]pyrimidine derivatives exhibited activity toward CDK9/CyclinT, while 4 of compounds had activity against Haspin. The best CDK9/CyclinT (IC50 of 0.38 μM) and Haspin (IC50 of 0.11 μM) activities were achieved by compounds 7d and 7f, resp. Hence, these compounds may be valuable starting points for development of new anti-cancer drugs.
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Keywords: 7-Deazapurine ; Anticancer ; CDK9/CylinT ; Haspin ; Protein kinase
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Purchased from AmBeed: 98437-24-2 ; 71597-85-8 ; 3680-69-1 ; 6165-68-0 ; 51067-38-0 ; 87199-18-6
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CAS No. : | 6165-68-0 |
Formula : | C4H5BO2S |
M.W : | 127.96 |
SMILES Code : | OB(C1=CC=CS1)O |
MDL No. : | MFCD00151850 |
InChI Key : | ARYHTUPFQTUBBG-UHFFFAOYSA-N |
Pubchem ID : | 2733960 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 8 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 34.14 |
TPSA ? Topological Polar Surface Area: Calculated from |
68.7 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.54 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-0.57 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.88 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.08 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-0.16 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.37 |
Solubility | 5.46 mg/ml ; 0.0427 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.55 |
Solubility | 3.57 mg/ml ; 0.0279 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.52 |
Solubility | 38.8 mg/ml ; 0.303 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
No |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.7 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
2.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.56 |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With potassium fluoride;bis(tri-t-butylphosphine)palladium(0); In tetrahydrofuran; at 60℃; for 1.5h; | 5-BROMO-2-HYDROXY-4-METHOXYBENZALDEHYDE obtained from Ex-lA (1.5 g, 6.5 mmol) and thiophene-2-boronic acid (0.91 g, 7.1 mmol) were dissolved in tetrahydrofuran (15 mL). Nitrogen was bubbled into the solution for 10 min followed by the sequential addition of potassium fluoride (0.80 G, 14 mmol, spray-dried) and bis (tri-t-butylphosphine) palladium (0) (0.033 g, 0.065 MMOL). The solution was immediately heated to 60 C and aged for 1.5 h. Upon completion, as determined by HPLC, the reaction was diluted with water (25 mL) and extracted with ethyl acetate (3 x 30 mL). The combined organic extracts were dried over sodium sulfate and concentrated to a brown solid. Silica gel chromatography (ethyl acetate/hexanes, 1: 3) gave 1.46 g (97%) of 2-hydroxy-4-methoxy-5-thiophen-2-yl-benzaldehyde as a yellow solid, m. p. 118-119 C.'H-NMR (300 MHz, CDC13) 8 11.48 (s, 1 H), 9.79 (s, 1 H), 7.72 (s, 1 H), 7.37 (dd, 1 H), 7.31 (dd, 1 H), 7.08 (dd, 1 H), 6.54 (s, 1 H), 3.98 (s, 3 H). Anal. Calcd. for CSH703S : C, 61.52 ; H, 4.30 ; S, 13.69. Found: C, 61.12 ; H, 4.34 ; S, 13.56. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate;tetrakis(triphenylphosphine)palladium (0); | REFERENCE EXAMPLE 83 To a mixture of <strong>[206551-41-9]methyl 3-bromo-2-fluorobenzoate</strong> (117 mg), 2-thiopheneboronic acid (83 mg) and 1,2-dimethoxyethane (2 ml) were added a 2M aqueous solution of sodium carbonate (0.83 ml) and tetrakis(triphenylphosphine)palladium(0) (29 mg) at ambient temperature. The mixture was heated for 3 hours at 90° C. After cooling, the reaction mixture was diluted with ethyl acetate (30 ml), and washed with water (20 ml*3) and brine (20 ml). The organic layer was dried over magnesium sulfate and filtered. After evaporation, the residue was chromatographed on a silica gel eluding with a mixture of ethyl acetate and n-hexane to give methyl 2-fluoro-3-(2-thienyl)benzoate (99 mg). Mass: 237 (m/z, (M+H)+) NMR(DMSO-d6, delta): 3.89 (3H, s), 7.1-7.3 (1H, m), 7.39 (1H, t, J=7.8 Hz), 7.6-7.9 (3H, m), 8.0-8.2 (1H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In water; ethyl acetate; | Step B 5-(Thien-2-yl)-thiophene-2-carboxaldehyde To a solution of thien-2-ylboronic acid (0.939 g, 7.34 mmol) and Na2 CO3 (2.40 g, 22.6 mmol) in water (75 mL) is added p-dioxane (75 mL). This mixture is treated sequentially with 5-carboxy-2-thiophenecarboxaldehyde (1.43 g, 7.48 mmol) and palladium (II) acetate (151 mg, 0.673 mmol) and allowed to stir at ambient temperature for 16 hours. The solvent is evaporated in vacuo. To the residue is added EtOAc (400 mL) and water (300 mL). The aqueous layer is acidified to pH 1 with 1.0N aq. HCl. The aqueous layer is extracted with EtOAc (2*200 mL). The organic extracts are combined, washing with brine (200 mL), 5percent aq. Na2 S2 O3 (200 mL), sat. aq. NaCl (200 mL), drying (Na2 SO4), and the solvent evaporation in vacuo affords the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
22% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; for 24h;Heating / reflux; | (1) Preparation of 3,5-Dibromo-2,2'-Bithiophene Tetrakis(triphenylphosphine)palladium (3 mmol) and 100 mL of an aqueous 2N sodium carbonate solution were added to a solution of 2-thiophene-boric acid (5.0 mmol) and <strong>[3141-24-0]2,3,5-tribromothiophene</strong> (100 mmol) in a mixture of 200 mL of toluene and 100 mL of ethanol in a nitrogen atmosphere. The resulting mixture was refluxed for 24 hours. The reaction mixture was combined with water, and extracted with toluene. The extract solution was washed with water, and dried over magnesium sulfate. The solvent was evaporated to obtain a crude product. The crude product was purified by column chromatography and by recrystallization from hexane to obtain the intended product (22.1 mmol) in a 22% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In ethanol; toluene;Inert atmosphere; Reflux; | General procedure: Bromo-2-methylisoindolin-1-one (520 mg, 2.30 mmol) and thiophene-2-boronic acid (442mg, 3.45 mmol) were dissolved in a mixure of toluene (12 mL) and EtOH (6 mL). A solution of 2 M Na2CO3 (3 mL) and Pd(dppf)C12 (94 mg, 0.12 mmol) were added and the entire mixture heated at reflux under N2 for 2 h. Additional thiophene-2-boronic acid (294 mg, 2.30 mmol) was added and reflux continued under N2 overnight. Upon cooling, themixture was diluted with water (100 mL) and extracted with CH2C12 (6x50 mL). The combined organic fractions were dried (Na2SO4), filtered, and the solvent removed under reduced pressure to give a crude solid which was purified by flash column chromatography on silica gel (EtOAc as eluant). The title compound was isolated as a light-brown solid (510 mg, 97percent). ?H NMR [400 MHz, (CD3)2S0] 8 7.87 (s, 1 H), 7.77 (dd, J? 7.9, 1.6 Hz,1 H), 7.67 (dd, J 7.9, 0.3 Hz, 1 H), 7.61-7.66 (m, 2 H), 7.18 (dd, J 5.0, 1.4 Hz, 1 H),4.49 (s, 2 H), 3.08 (s, 3 H). LRMS (APCI) calcd for C13H,2NOS 230 (MH), found 230. |
97% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In ethanol; toluene;Inert atmosphere; Reflux; | 5-Bromo-2-methylisoindolin-1-one (520 mg, 2.30 mmol) and thiophene-2-boronic acid (442mg, 3.45 mmol) were dissolved in a mixure of toluene (12 mL) and EtOH (6 mL). A solutionof 2 M Na2CO3 (3 mL) and Pd(dppf)Cl2 (94 mg, 0.12 mmol) were added and the entiremixture heated at reflux under N2 for 2 h. Additional thiophene-2-boronic acid (294 mg, 2.30mmol) was added and reflux continued under N2 overnight. Upon cooling, the mixture wasdiluted with water (100 mL) and extracted with CH2Cl2 (6x50 mL). The combined organicfractions were dried (Na2SO4), filtered, and the solvent removed under reduced pressure togive a crude solid which was purified by flash column chromatography on silica gel (EtOAcas eluant). The title compound was isolated as a light-brown solid (510 mg, 97percent). 1H NMR[400 MHz, (CD3)2SO] delta 7.87 (s, 1 H), 7.77 (dd, J = 7.9, 1.6 Hz, 1 H), 7.67 (dd, J = 7.9, 0.3Hz, 1 H), 7.61-7.66 (m, 2 H), 7.18 (dd, J = 5.0, 1.4 Hz, 1 H), 4.49 (s, 2 H), 3.08 (s, 3 H).LRMS (APCI+) calcd for C13H12NOS 230 (MH+), found 230. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With tris-(dibenzylideneacetone)dipalladium(0); sodium carbonate; tricyclohexylphosphine; In water; N,N-dimethyl-formamide; at 130℃; for 1h;Inert atmosphere; Microwave irradiation; | <strong>[4532-25-6]7-chloroimidazo[1,2-a]pyridine</strong> (5) (300 mg, 1.97 mmol) was dissolved in 8:1 DMF:H2O (13.1 mL) in a microwave vial affixed with a magnetic stir bar. Thiophen-2-ylboronic acid was added followed by sodium carbonate (834 mg, 7.86 mmol). The reaction mixture was degassed with argon. Pd2(dba)3 (36 mg, 0.039 mmol) and P(Cy)3 (33 mg, 0.118 mmol) was added to the reaction mixture and the vial was sealed. The reaction was heated by microwave irradiation to 130 C for 1 h. After, the reaction mixture was diluted with ethyl acetate and washed three times with saturated sodium bicarbonate and three times with deionized water. The organic layer was dried over anhydrous sodium sulfate and the solvent was removed in vacuo. The crude product was absorbed onto silica. The product was purified via flash chromatography utilizing a DCM/MeOH gradient and isolated as a brown solid (223 mg, 59%). 1H NMR (400 MHz, Chloroform-d) delta 8.07 (dd, J = 7.0, 2.7 Hz, 1H), 7.81 (s, 1H), 7.63 (s, 1H), 7.54 (s, 1H), 7.38 (s, 1H), 7.35-7.30 (m, 1H), 7.14-7.07 (m, 1H), 7.03 (d, J = 5.4 Hz, 1H). 13C NMR (100 MHz, Chloroform-d) delta 145.57, 142.02, 134.43, 130.87, 128.29, 125.88, 125.59, 124.20, 112.82, 112.33, 111.40. ESIMS m/z [M+H]+ 201. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 155℃; for 0.333333h;Microwave irradiation; | General procedure: To a mixture of compound 7a (1 mmol), the corresponding (het)arylboronic acid 9 (1.2 mmol), Pd(PPh3)4 (58 mg, 0.05 mmol) in degassed THF (3 mL), a solution of K2CO3 (346 mg, 2.5 mL) in water (4 mL) were added. The reaction mixture was microwave irradiated at 155 C (250 W) for 20 min, then solvent was removed in vacuo. Products were isolated by column chromatography (elution with ethyl acetate-hexane, 1 : 2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; water; for 8h;Inert atmosphere; Reflux; | General procedure: Compound 1: A mixture of 2-Br-phen (0.80 g, 3.10 mmol), 2-thiophenylboronic acid (0.42 g, 3.28 mmol), Pd(PPh3)4 (0.12 g, 0.10 mmol) and Cs2CO3 (3.03 g, 9.30 mmol) was dissolved in a mixture of dioxane (40 mL) and H2O (8 mL), placed into a degassed three-necked flask and refluxed under an argon atmosphere for 8 h. After the solution was cooled to room temperature, the solvent was removed under reduced pressure and the residue was dissolved in CHCl3 (50 mL), washed with excess water, and dried with anhydrous Na2SO4. The desired compound 1 was finally separated as light yellow solid by silica gel column chromatography using CHCl3/petroleum ether (v:v 5:1) as the eluent in a yield of 0.71 g (87%). Similarly, compounds 3 and L1 were obtained via the same synthetic method in the yields of 42 and 77%, respectively. Compound 3: 1H NMR (300 MHz, CDCl3) delta: 9.45 (d, 1H, J=2.3 Hz, phen), 9.20 (dd, 1H, J=4.4, 1.7 Hz, phen), 8.35 (d, 1H, J=2.3 Hz, phen), 8.25 (dd, 1H, J=8.1, 1.7 Hz, phen), 7.79 (s, 2H, phen), 7.64-7.57 (m, 2H, phenthienyl), 7.45 (dd, 1H, J=5.1, 1.1 Hz, thienyl), 7.20-7.18 (m, 1H, thienyl). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With potassium phosphate; In tetrahydrofuran; water; for 4h;Inert atmosphere; Reflux; | Charge a four-neck flask with the above-prepared compound (c) (1.5 g, 2.2 mmol), 2-thiophene boronic acid (630 mg, 4.9 mmol), Pd(Pt13u3)2 (150 mg, 0.22 mmol), K3P04 aqueous solution (10 ml, 20% by weight), and THF (50 nil), and reflux for 4 hours under Ar atmosphere. Cool thereaction liquid to room temperature and wash it with MeOR. Thus, a blue solid (1.3 g, 85%) is obtained. mlz=689.2 (M+H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
39.1 g | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In methanol; Dimethyl ether; water; for 10h;Reflux; | 4-Bromo-2,6-difluoroanisole (25.3 ml, 187.6 mmol) was dissolved in dimethyl ether (600 ml) and degassed for 30 minutes. Potassium carbonate aqueous solution (K 2 CO 3, 2M, 100 ml) was added to the mixed solution, and gas removal After that, tetrakis (triphenylphosphine) palladium (Pd (PPh3) 4, 9.0 g, 7.8 mmol) was added and degassed for 1 hour,And the mixture was stirred and refluxed. Subsequently, thiophene-2-boronic acid (20 g, 156.3 mmol) was dissolved in methanol (200 ml)The mixture was slowly injected into the mixed solution using a dropping funnel, followed by stirring for 10 hours. Next, the reaction mixtureThe reaction was terminated by pouring water into excess water, extracted with dichloromethane, dried and passed through a silica gel columnWater was obtained as a white solid (39.1 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | With palladium diacetate; potassium carbonate; triphenylphosphine; In water; N,N-dimethyl-formamide; at 100℃; for 24h;Inert atmosphere; Sealed tube; | <strong>[16870-28-3]2-hydroxy-4-iodobenzoic acid</strong> (0.265 mmol), 40.69 mg of 2-thienylboronic acid (0.318 mmol), 109.89 mg of K2CO3 (0.795 mmol), 10.49 mg of PPh3 (0.040 mmol), 2.91 mg of Pd(OAc)2 (0.013 mmol), 1:1 DMF: H2O (2 ml) were used. Purification by flash chromatography was performed using as the mobile phase DCM/ MeOH (20:1 ?9:1 gradient elution). Compound 85 was obtained as a yellow solid. Yield after purification: 51 % (30 mg). Melting point = 225 C 1H NMR (400 MHz, DMSO-d6) delta 7.74 (d, J = 8.4 Hz, 1H), 7.57 (dd, J = 5.1, 1.1 Hz, 1H), 7.54 (dd, J = 3.6, 1.2 Hz, 1H), 7.13 (dd, J = 5.1, 3.7 Hz, 1H), 7.05-6.99 (m, 2H). 13C NMR (101 MHz, DMSO-d6) delta 172.01 (CO), 162.95 (C), 143.33 (C), 138.30 (C), 131.33 (CH), 128.50 (CH), 126.72 (CH), 124.89 (CH), 117.40 (C), 114.95 (CH), 112.94 (CH). HRMS (TOF, ES-): Calculated for C11H7O3S (M-H)-: m/z 219.0116. 219.0105 found (deviation -5.0 ppm). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85.9% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate tribasic trihydrate; In N,N-dimethyl-formamide; at 100℃; for 10h;Inert atmosphere; | General procedure: Toa degassed solution of <strong>[175205-81-9]2-bromo-4-(trifluoromethyl)pyridine</strong> (500 mg,2.21 mmol) and the corresponding boric acid (1.2 equiv) or boric acidester (SM-4, 1.2 equiv) in dry DMF (10 mL) were added Pd(dppf)Cl2(50 mg) and K3PO4*3H2O (1.18 g, 4.42 mmol). After 10 h heating at100 °C, the reaction mixture was cooled to room temperature, dilutedwith EtOAc (50 mL) and filtered through a pad of Celite. The filtratewas washed with H2O and brine. After the solvent was removed, theresidue was purified by column chromatography on silica gel, elutedwith EtOAc/hexanes (1:50, v/v) to give corresponding cyclometalatedligands:cf3thp: (0.48 mg, yield: 85.9percent), white solid. 1H NMR (400 MHz,CDCl3) delta (ppm) 8.97 (d, J=7.5 Hz, 1H), 7.66?7.69 (m, 2H), 7.44 (s,1H), 7.31?7.34 (m, 2H). 13C NMR (101 MHz, CDCl3) delta (ppm) 154.00,150.71, 143.53, 139.48, 137.21, 129.03, 128.44, 125.93, 117.30,114.46. HRMS (m/z): calcd for C10H6F3NS requires [M+H]+ 234.5690,found: 234.5678. Elemental anal. calcd. for C14H8F3NS: C, 52.40; H,2.64; N, 6.11. Found: C, 52.34; H, 2.66; N, 6.12percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With potassium fluoride; tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; toluene; at 90℃; | The organic phase tetrahydrofuran/toluene solution (THF: Toluene = 1:1), freshly prepared alkali solution (K2CO3/KF (2M) aqueous solution) were dried in advance, and the two mixed solvents were bubbled and deaerated for 2 h. Construction equipment: The dry 250mL double-necked flask, magneto, and condensate tube assembly number, and the sealing system only left the sample port. Weigh <strong>[67665-47-8]2,2'-dibromospirobifluorene</strong> (1.00g, 2.10mmol), thiopheneboronic acid (1.07g, 8.40mmol) in a dry two-necked flask to ensure a sealed system, vacuum and nitrogen gas 2-3 times The tin foil wrapping device is used for light protection. Tetrakistriphenylphosphine palladium (0.19 g, 0.17 mmol) was quickly weighed and quickly added to the reaction flask under a nitrogen atmosphere, vacuumed again and then protected with a nitrogen balloon. 50 mL of the organic phase was injected into the flask to dissolve the drug. The reaction device was heated to 90 C in an oil bath, and then 8.4 mL of lye was added. The magnet was stirred, and the plate was monitored. The reaction was stopped after the reaction of the starting material. The reaction was quenched, the organic phase was extracted with dichloromethane, dried over anhydrous sodium sulfate and filtered, and then evaporated. The silica gel column was purified by column chromatography (EtOAc: methylene chloride = 5:1 to 3:1) to yield white solid powder b (0.63g, 1.30mmol, 62%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
24% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In methanol; toluene;Inert atmosphere; Reflux; | General procedure: <strong>[1458-01-1]Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate</strong> 2 (1 eq.) was combined with K2CO3 (10 eq.), the appropriate (het)aryl boronic acid (1.5 eq.) and Pd(PPh3)4 (5 mol%) in a two-neck round bottom flask. The flask was connected to a condenser and purged with nitrogen. A 4:1 mixture of anhydrous toluene: MeOH (60 mL) was added via syringe and the reaction mixture was heated at reflux for 0.5-18 h. The mixture was allowed to cool to room temperature and filtered through Celite (10 x 3 cm, eluting with 3 x 20 mL EtOAc). The filtrate was evaporated to dryness and the residue purified by silica gel flash column chromatography using EtOAc/pet spirit. |
Tags: 6165-68-0 synthesis path| 6165-68-0 SDS| 6165-68-0 COA| 6165-68-0 purity| 6165-68-0 application| 6165-68-0 NMR| 6165-68-0 COA| 6165-68-0 structure
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Precautionary Statements-General | |
Code | Phrase |
P101 | If medical advice is needed,have product container or label at hand. |
P102 | Keep out of reach of children. |
P103 | Read label before use |
Prevention | |
Code | Phrase |
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P210 | Keep away from heat/sparks/open flames/hot surfaces. - No smoking. |
P211 | Do not spray on an open flame or other ignition source. |
P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
P230 | Keep wetted |
P231 | Handle under inert gas. |
P232 | Protect from moisture. |
P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
P235 | Keep cool |
P240 | Ground/bond container and receiving equipment. |
P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
P242 | Use only non-sparking tools. |
P243 | Take precautionary measures against static discharge. |
P244 | Keep reduction valves free from grease and oil. |
P250 | Do not subject to grinding/shock/friction. |
P251 | Pressurized container: Do not pierce or burn, even after use. |
P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
P262 | Do not get in eyes, on skin, or on clothing. |
P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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