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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
p-Anisaldehyde (4-methoxybenzaldehyde), an extract from Pimpinella anisum seeds, exhibits antifungal activity against a number of yeast and mold strains in laboratory media, fruit purees and fruit juices.
Synonyms: p-Anisaldehyde; Anisaldehyde; 4-Anisaldehyde
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Selective and Cell-Active PBRM1 Bromodomain Inhibitors Discovered through NMR Fragment Screening
Shifali Shishodia ; Raymundo Nuñez ; Brayden P. Strohmier ; Karina L. Bursch ; Christopher J. Goetz ; Michael D. Olp , et al.
Abstract: PBRM1 is a subunit of the PBAF chromatin remodeling complex that uniquely contains six bromodomains. PBRM1 can operate as a tumor suppressor or tumor promoter. PBRM1 is a tumor promoter in prostate cancer, contributing to migratory and immunosuppressive phenotypes. Selective chemical probes targeting PBRM1 bromodomains are desired to elucidate the association between aberrant PBRM1 chromatin binding and cancer pathogenesis and the contributions of PBRM1 to immunotherapy. Previous PBRM1 inhibitors unselectively bind SMARCA2 and SMARCA4 bromodomains with nanomolar potency. We used our protein-detected NMR screening pipeline to screen 1968 fragments against the second PBRM1 bromodomain, identifying 17 hits with Kd values from 45 μM to >2 mM. Structure–activity relationship studies on the tightest-binding hit resulted in nanomolar inhibitors with selectivity for PBRM1 over SMARCA2 and SMARCA4. These chemical probes inhibit the association of full-length PBRM1 to acetylated histone peptides and selectively inhibit growth of a PBRM1-dependent prostate cancer cell line.
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Purchased from AmBeed: 77326-36-4 ; 104-87-0 ; 2148-56-3 ; 63329-53-3 ; 1591-37-3 ; 387-45-1 ; 936-08-3 ; 1123-56-4 ; 2819989-75-6 ; 703-80-0 ; 1885-29-6 ; 115643-59-9 ; 15764-16-6 ; 487-68-3 ; 145737-61-7 ; 5779-95-3 ; 88-68-6 ; 6575-11-7 ; 77326-62-6 ; 88-65-3 ; 4635-59-0 ; 5779-94-2 ; 56043-01-7 ; 5779-93-1 ; 1591-38-4 ; 446-52-6 ; 62803-47-8 ; 1885-31-0 ; 620-23-5 ; 54166-95-9 ; 22179-72-2 ; 529-20-4 ; 100-52-7 ; 123-11-5 ; 1711-06-4 ; 454-89-7 ; 170875-01-1 ; 883032-29-9 ; 2819989-61-0 ; 1915012-21-3 ; 2819989-58-5 ; 2819989-60-9 ; 2819989-57-4 ; 2819989-68-7 ; 2819989-67-6 ; 111478-13-8 ; 73096-42-1 ; 2835-78-1 ; 118-92-3 ; 22458-07-7 ; 80258-99-7 ; 24782-64-7 ; 1108790-90-4 ; 175204-03-2 ; 97-96-1 ; 780802-33-7 ; 89-98-5
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Design, synthesis and evaluation of thienopyridines as ligands of adenosine receptors
Nkomba, Gaofenngwe ;
Abstract: Despite the availability of various classes of antiepileptic drugs (AEDs), about one third of epileptic patients do not experience satisfactory seizure control with present treatments. This has been an important drive in the search for alternative epilepsy treatment. The endogenous nucleoside adenosine is a known anticonvulsant through activation of adenosine A1 receptors. The development of adenosine derivatives such as N6-cyclohexyladenosine (CHA) as anticonvulsants had limitations which include pronounced peripheral side effects, mainly cardiovascular effects. Over the years, non-nucleoside agonists have been investigated as an alternative set of compounds which are highly potent and selective to specific adenosine receptor (AR) subtypes. The aim of this study was to investigate the use of amino-3,5-dicyanopyridine and thieno[2,3- b]pyridine derivatives as potential A1 AR agonists. A total of 23 test compounds were synthesised (6a–s and 7a–d) and 7 of these were novel (6d and 6k–p), while 4 compounds (7a–d) have been synthesised before but have never been tested for AR affinity. The effect of intramolecular cyclisation that occurs during synthesis of thieno[2,3-b]pyridines from the intermediate compounds, amino-3,5-dicyanopyridines, in relation to AR binding was evaluated. Overall, amino-3,5-dicyanopyridine displayed superior activity towards rA1 ARs compared to thieno[2,3]pyridines. The general poor activity of thieno[2,3-b]pyridines suggest that the intramolecular cyclisation results in molecular stiffening or rigidity which negatively affects binding to the receptors, perhaps, due to steric hindrance. For instance, compound 6f (open ring) had a six-fold better inhibition constant (Ki) value of 48 nM for the A1 subtype compared to its closed ring counterpart compound 7d (rA1Ki = 305 nM). Generally, most amino-3,5- dicyanopyridines exhibited greater affinity toward the rA1 AR (Ki
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Keywords: Epilepsy ; Antiepileptic drugs ; Adenosine A1/A2A receptor agonists ; Amino-3 ; 5- dicyanopyridine derivatives ; Thieno[2 ; 3-b]pyridine derivatives ; Intramolecular cyclisation
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CAS No. : | 123-11-5 |
Formula : | C8H8O2 |
M.W : | 136.15 |
SMILES Code : | O=CC1=CC=C(OC)C=C1 |
Synonyms : |
p-Anisaldehyde; Anisaldehyde; 4-Anisaldehyde
|
MDL No. : | MFCD00003385 |
InChI Key : | ZRSNZINYAWTAHE-UHFFFAOYSA-N |
Pubchem ID : | 31244 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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 |
---|---|---|
69% | To a solution of 2.67 g (15.0 mmol, 1 eq.) of pivalamide VII and 6.8 mL (45.0 mmol, 3 eq.) of TMEDA in 120 mL of diethylether, cooled to -78°C, were added 18.0 mL (45.0 mmol, 3 eq., 2.5 M in hexane) of BuLi. After 15 minutes, the solution was brought back to -24°C and stirred 2 hours. Then, the mixture was cooled down to - 78°C before addition of 4.0 mL (33.0 mmol, 2.2 eq) of p-anisaldehyde in 60 mL of THF. The reaction was brought back to 0°C and stirred 2 hours before being stirred at room temperature over night. Then, 120 mL of water were added. The aqueous layer was extracted with 3 x 80 mL of dichloromethane. The organic phase was dried, filtered and concentrated. Precipitation in 30 mL of PE/DCM 1 :1 afforded 3.26 g (10.4 mmol, 69percent) of XIV as a white powder. Rf=0.16 (PE/EtOAc 1 :2). 1H NMR (300 MHz): delta = 9.57 (s, 1 H), 8.36 (d, J = 5.7 Hz, 1 H), 8.23 (d, J = 5.7 Hz, 1 H), 7.87 (s, 1 H), 7.18 (d, J = 8.5 Hz, 2 H), 6.89 (broad, 1 H), 6.83 (d, J = 8.3 Hz, 2 H), 5.78 (s, 1 H), 3.77 (s, 3 H), 1 .08 (s, 9 H) ppm. 13C NMR (75 MHz): delta = 177.9, 159.4, 149.8, 148.4, 145.6, 133.0, 127.5, 126.4, 115.3, 114.0, 73.2, 55.5, 40.2, 27.2 ppm | |
69% | To a solution of 2.67 g (15.0 mmol, 1 eq.) of pivalamide VII and 6.8 mL (45.0 mmol, 3 eq.) of TMEDA in 120 mL of diethylether, cooled to -78°C, were added 18.0 mL (45.0 mmol, 3 eq., 2.5 M in hexane) of BuLi. After 15 minutes, the solution was brought back to -24°C and stirred 2 hours. Then, the mixture was cooled down to - 78°C before addition of 4.0 mL (33.0 mmol, 2.2 eq) of p-anisaldehyde in 60 mL of THF. The reaction was brought back to 0°C and stirred 2 hours before being stirred at room temperature over night. Then, 120 mL of water were added. The aqueous layer was extracted with 3 x 80 mL of dichloromethane. The organic phase was dried, filtered and concentrated. Precipitation in 30 mL of PE/DCM 1 :1 afforded 3.26 g (10.4 mmol, 69percent) of XIV as a white powder. Rf=0.16 (PE/EtOAc 1 :2). 1H NMR (300 MHz): delta = 9.57 (s, 1 H), 8.36 (d, J = 5.7 Hz, 1 H), 8.23 (d, J = 5.7 Hz, 1 H), 7.87 (s, 1 H), 7.18 (d, J = 8.5 Hz, 2 H), 6.89 (broad, 1 H), 6.83 (d, J = 8.3 Hz, 2 H), 5.78 (s, 1 H), 3.77 (s, 3 H), 1 .08 (s, 9 H) ppm. 13C NMR (75 MHz): delta = 177.9, 159.4, 149.8, 148.4, 145.6, 133.0, 127.5, 126.4, 115.3, 114.0, 73.2, 55.5, 40.2, 27.2 ppm |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | Step 2: 2- [2- (4-Methoxy-phenyl)-vinyl]-nicotinic acid A mixture of 5.0 G (30.26 MMOL) of the previous compound and 7.74 G (56.8 MMOL) of ANISALDEHYDE is heated at 120°C. 3.9 G (28.6 MMOL) of anhydrous zinc chloride are added- and the whole is heated at 180°C allowing the ethanol formed to be expelled. After 2 hr a solid crystallises and a solution of 4.9 G of sodium hydroxide in 41 ml of water is added. After stirring to disgregation, the inorganic salts are filtered and the filtrate is washed with ethyl ether and neutralised with acetic acid. The solid precipitated is filtered, washed with water and recrystallised from ethanol. Yield : 5.2 G (67 percent). | |
42% | A mixture of NaH (60percent dispersion in mineral oil, 7.4 g, 0.185 mole), tert-butanol (11.12 g, 0.15 mole), and anhydrous DMF (100 mL) was carefully warmed at 80° C. until gas evolution ceased, then was cooled to 0° C. under argon. A solution of <strong>[1721-26-2]ethyl 2-methylnicotinate</strong> (7.7 mL, 0.050 mole) in anhydrous DMF (17 mL) was added dropwise over 3 min, and the reddish-orange mixture was stirred at 0° C. for 1 hr. A solution of para-anisaldehyde (7.3 mL, 0.060 mL) in anhydrous DMF (17 mL) was added dropwise over 3 min, and the reaction was allowed to warm to RT. The mixture was stirred overnight, then was poured into ice water (200 mL), and the solution was acidified to pH 6 with glacial acetic acid. The volume was adjusted to 1 L with H2O, the flask was scratched with a glass rod, and the mixture was allowed to stand at RT for several hr, then in the refrigerator overnight. The solid was collected by suction filtration and washed with H2O. Recrystallization from boiling absolute EtOH gave the title compound (5.31 g, 42percent, two crops) as yellow needles: 1H NMR (250 MHz, DMSO-d6) delta 8.70 (dd, J=4.6, 1.7 Hz, 1H), 8.18 (dd, J=7.9, 1.7 Hz, 1H), 7.95 (d, J=15.8 Hz, 1H), 7.83 (d, J=15.8 Hz, 1H), 7.57 (d, J=8.7 Hz, 2H), 7.34 (dd, J=7.9, 4.6 Hz, 1H), 6.99 (d, J=8.7 Hz, 2H), 3.79 (s, 3H); MS (ES) m/e 256 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70.1% | With diisobutylaluminium hydride; In methanol; toluene; benzene; | (1)2-(4-Methylbenzyloxy)methyl-2-propenol A mixture of p-anisaldehyde (17.31 g, 0.127 mol), <strong>[3513-81-3]2-methylene-1,3-propanediol</strong> (14.00 g, 0.159 mol), and p-TsOH H2 O (121 mg, 0.64 mmol) in dry PhH (100 ml) was stirred and heated at reflux, and the water generated was azeotropically removed in a theoretical amount using a Dean-Stark apparatus. After 70 ml of PhH was distilled off, the resultant red PhH solution containing 2-(4-methoxyphenyl)-5-methylene-1,3-dioxane was cooled with salt-ice, and a solution of diisobutylaluminum hydride (DIBAL-H) in PhMe (1.02M, 100 ml and 1.50M, 67.0 ml; total 0.203 mol) was added dropwise under an atmosphere of N2; at the point when 20 ml of the PhMe solution of DIBAL-H was added, the reaction mixture changed from deep red to light yellow. After the addition was complete, the reaction mixture was allowed to stirr at room temperature overnight. The reaction mixture was ice-cooled, and MeOH (23 ml) was added carefully. H2 O (12 ml) was, then, added dropwise, wherein the mixture became thick and gelatinous, and finally granular. After the stirring was continued at room temperature for an hour, the mixture was filtered through a pad of Celite. The filter cake was washed with PhMe thoroughly. The combined filtrate and washings were dried (MgSO4), and concentrated in vacuo at a bath temperature of 65 C. to give a pale yellow oil (24.88 g). This was distilled in vacuo to give title compound (18.52 g, 70.1percent) as a colorless oil. bp 123-147 C./0.80-0.90 mm; IRmax (film): 3420(s), 1615(s), 1515(s), 1250(s), 1070(s), 1035(s), 918(m), 820(s) cm-1; 1 H-NMR delta: 7.26(d, J=8.8 Hz, 2H), 6.88(d, J=8.8 Hz, 2H), 5.19(br.s, 1H), 5.14(br.s, 1H), 4.45(s, 2H), 4.19(s, 2H), 4.07(s, 2H), 3.81(s, 3H), 1.98(br.s., 1H) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44% | General procedure: To a solution of the corresponding aromatic aldehyde (0.27 mmol) in EtOH (0.5 mL) was added urea (0.54 mmol) and CuSO4·5H2O (0.054 mmol). The mixture was stirred at 80 °C for 15 minutes before tetrahydrocurcumin or tetrahydrodemethoxycurcumin (0.27 mmol) was added. The reaction mixture was continued stirring for 24 hours and quenched with water (2 mL). The solution was washed with water (10 mL) and extracted with EtOAc (415 mL). The combined organic phases were washed with brine, dried over MgSO4 and concentrated under reduced pressure to afford crude product as a yellow brown oil. Purification was accomplished by column chromatography eluting with 60percent-75percent EtOAc/hexane to furnish compounds 8-17. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With acetic acid; In ethanol; at 80℃; for 0.166667h;Microwave irradiation; | General procedure: 2-(2-Arylidenehydrazino)-6-fluorobenzothiazoles 6a-r. General Procedure D. A mixture of compound 2 (0.0549 g, 0.0003 mol), the appropriate aromatic aldehyde (0.00033 mol) and glacial acetic acid (0.1 mL) in ethanol (5 mL) was heated under microwave (20 W) at 80 °C for 10 min. On cooling, the precipitated solid was collected by filtration, washed with water, dried and crystallized from the appropriate solvent to give the desired compounds 6a-r. |
In ethanol; at 70 - 80℃; for 3h; | General procedure: The mixture of <strong>[78364-55-3]6-fluoro-2-hydrazinylbenzo[d]thiazole</strong> (2) (0.01 mol) and benzalde-hyde/substituted benzaldehyde (0.01 mol) was reuxed in ethanol (15 ml) at 70?80 °C for 3 h. The separated product obtained was ltered off, washed withdistilled water and recrystallized from methanol to give the correspondinghydrazone. The product obtained was further dissolved in acetic acid (20 ml) atroom temperature followed by the addition of sodium acetate (0.5 g). Bromine(2 mmol) in acetic acid (10 ml) was added dropwise to the reuxing reactionmixture. After 1 h, the mixture was poured onto crushed ice (100 g). The precipitateobtained was ltered off and crystallized from ethanol-dimethylformamide (1:1) togive crystals of (3a?3t). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
10%; 54% | To a solution of tetrahydrocurcumin (0.134 mmol,50 mg), p-TsOH?H2O (0.027 mmol, 5.11 mg), and 4 A molecular sieves (72 mg) in EtOH (0.34 mL) wasadded p-methoxybenzaldehyde (0.10 mmol, 13.71 mg). The mixture was stirred at 80 °C for 20 min beforeammonium acetate (0.134 mmol, 10.33 mg) was added. The reaction mixture was stirred at 80 °C for 24 hbefore being quenched with water (5 mL) and extracted with EtOAc. The combined organic phases werewashed with brine, dried over Na2SO4 and concentrated under reduced pressure to afford the crude productas a yellow oil. Purification was accomplished by column chromatography eluting with 75percentEtOAc/Hexane to give the THC-DHP 1c as a yellow waxy solid. Yield: 10percent; IR (max, cm-1): 3388, 2930,1601, 1512, 1428, 1031; 1H NMR (400 MHz, CDCl3) delta: 6.89 (2H, d, J = 8.4 Hz, ArH), 6.80 (2H, d, J =8.4 Hz, ArH), 6.75 (2H, d, J = 7.9 Hz, ArH), 6.68 (2H, d, J = 8.5Hz, ArH), 6.60-6.55 (8H, m, ArH), 5.49(2H, br s, 2×ArOH), 5.42 (2H, br s, 2×ArOH), 5.16 (1H, br s, NH), 4.90 (1H, s, CH), 3.77 (6H, s,2×OCH3), 3.76 (6H, s, 2×OCH3), 3.75 (3H, s, OCH3), 2.80-2.72 (8H, m, 2×CH2CH2CO), 2.64 (4H, t, J =6.4 Hz, 2×CH2CH2Ar), 2.60-2.50 (4H, m, 2×CH2CH2Ar); 13C NMR (100 MHz, CDCl3) delta: 199.9 (2×CO),158.5 (CArOCH3), 146.8 (2×CArOCH3), 146.5 (2×CCO), 145.8 (2×CArOCH3), 144.5 (CArCH), 144.4(2×CArOH), 144.0 (2×CArOH), 133.6 (2×CArCH2), 132.6 (2×CArCH2), 128.3 (2×CHAr), 121.1 (2×CHAr), 121.0 (2×CHAr), 114.6 (2×CHAr), 114.4 (2×CHAr), 114.1 (2×CHAr), 113.0 (2×CNH), 111.4 (2×CHAr),111.3 (4×CHAr), 56.1 (2×OCH3), 56.0 (2×OCH3), 55.4 (OCH3), 43.0 (2×CH2CO), 35.0 (CH), 34.2(2×CH2CNH), 30.4 (2×CH2Ar), 29.9 (2×CH2Ar). ESMS m/z: 844.5 [M+H]+ (100); HRMS: Calcd. forC50H52NO11: 842.3546, found 842.3545. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium tris(acetoxy)borohydride; In acetic acid; 1,2-dichloro-ethane; | To a mixture of 7-amino-3,4-dihydroisoquinolin-l(2H)-one (122mg, 0.752 mmol) and p-methoxybenzaldehyde (0.2 mL, 1.65 mmol) in DCE (2mL) was added AcOH (4drops) and NaBH(OAc)3 (349 mg, 1.65mmol). After stirring overnight, additional NaBH(OAc)3 (100 mg) was added and stirred for 4 h. Saturated NaHC03 solution and ethyl acetate was added. The organic layer was washed with water and dried over MgSC and concentrated under reduced pressure. The product was purified by silica gel column chromatography (0 to 100% EtOAc in hexane) ESI-MS: 403.9 (MH+). The dihydrosioquinolinone (39mg, 0.096 mmol), methyl (S)-2- (2,6-dichlorobenzamido)-3-(4-iodophenyl)propanoate (46mg, 0.096 mmol), xantphos (3.3 mg, 0.0058 mmol), Pd2dba3 (2mg, 0.002 mmol), and CS2CO3 (44mg, 0.13 mmol) were dissolved in dioxane (ImL). The reaction vessel was degassed and heated at 65 oC for lh and kept stirring at 100 oC for 4 h. The reaction mixture was cooled and partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over MgSC and concentrated. The product was purified by preparative TLC. ESI-MS: 752.9 (MH+). The bis PMB amine (14mg, 0.018mmol) was stirred in TFA (ImL) at 65 oC for 3h and concentrated. ESI-MS: 512.8 (MH+). To a mixture of crude aniline (18mg) in DMF (ImL) was added trimethylamine (0.03 mL), bis-Boc thiourea (16mg, 0.06 mmol), and then CuC^ (8mg, 0.06 mmol). After 30min, water and EtOAc were added and the organic layer was separated, concentrated and purified by preparative HPLC. ESI-MS: 754.9 (MH+). The bis-guanidine was stirred in TFA (50% in DCM, ImL) for 1.5h and concentrated to yield the guanidine (4mg). ESI-MS: 554.8 (MH+). To the crude methyl ester in THF (0.5 mL) was added aq. LiOH (1M, 0.06 mL). After 1.5h, the mixture was acidified with aq. HC1 (1M) and purified by RP-HPLC. condition: 19 100 mm Altantis T3 OBD, solvent A, solvent B', flow rate: 10 ml/min, gradient: 5% solvent B' for 5 min, 5% to 100% solvent B' for 25min, detection: 254nm) 19.5 min, ESI-MS: 540.8 (MH+) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | N4-Methoxybenzyl-fluorenylmethylcarbazate 2 was prepared according to a modification of the reductive amination procedure for carbazate synthesis (Boeglin, D.; Lubell,W. D. ?Aza-Amino Acid Scanning of Secondary Structure Suited for Solid-Phase PeptideSynthesis with Fmoc Chemistry and Aza-Amino Acids with Heteroatomic Side-Chains? J. Comb.Chem. 2005, 7(6), 864-878). A suspension of fluorenylmethylcarbazate (1) in EtOH (0.2 M) was treated with 100 mol percent of 4-methoxybenzaldehyde, heated at reflux for 2 h, and concentrated in vacuo. The resulting methylidene carbazate was dissolved in THE (0.2 M), treated successively with 110 mol percent AcOH and 110 mol percent NaBH3CN, stirred for 1 h, and treated with additionalNaBH3CN if necessary until completion of the reaction was observed by TLC. The mixture was concentrated in vacuo. The residue was dissolved in EtOAc, washed with aqueous KHSO4 (1M) and brine, dried over Na2SO4, and concentrated under reduced pressure to yield a white solid that was dissolved in EtCH and heated at reflux for 1 h. The mixture was concentrated under reduced pressure to yield a residue that was purified by flash chromatography to yieldcarbazate 2 (76 percent) as white solid: Rt 0.53 (30percent EtOAc); 1H NMR (300 MHz, CDCI3) 6 7.78 (d,J= 7.5 Hz, 2H), 7.58 (d, J= 7.6 Hz, 2H), 7.45?7.27 (m, 6H), 6.87 (d, J= 7.2, 2H), 6.35 (bs, 1H),4.48 (bs, 2H), 4.24 (t, J= 2.3 Hz, 1H), 3.94 (bs, 2H), 3.81 (s, 3H); ?3C NMR (75 MHz, CDCI3) 6159.2, 157.2, 143.7, 141.4, 130.3, 129.4, 127.8, 127.1, 125.0, 120.1, 113.9, 66.9, 55.4, 47.2;HRMS mfz calculated for C23H22N203 [M÷HJ 375.1703; found 375.1697. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With 3-((3,5-bis(trifluoromethyl)phenyl)amino)-4-(((S)-(6-methoxyquinoline-4-yl))((1S,2S,4S,5R-5-vinylquinuclidine-2-yl)methyl)amino)cyclobutan-3-ene-1,2-dione; In neat liquid; at 50℃; for 48h; | General procedure: Reactions were carried out with <strong>[66521-66-2]4-(pyridin-3-yl)pyrimidin-2-amine</strong> 1 (0.50 mmol), aldehyde 2 (0.50 mmol) and malonate 3 (5 mmol) in the presence of catalyst III or IV (10 molpercent) at 50 °C and stirred for 48h. After completion of the reaction (as observed by TLC), the crude product was purified by preparative TLC (GF254 silica gel: hexane/EtOAc = 7/1), giving the target chiral product |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With quinine; In neat liquid; at 50℃; for 48h; | General procedure: Reactions were carried out with <strong>[66521-66-2]4-(pyridin-3-yl)pyrimidin-2-amine</strong> 1 (0.50 mmol), aldehyde 2 (0.50 mmol) and malonate 3 (5 mmol) in the presence of catalyst III or IV (10 molpercent) at 50 °C and stirred for 48h. After completion of the reaction (as observed by TLC), the crude product was purified by preparative TLC (GF254 silica gel: hexane/EtOAc = 7/1), giving the target chiral product |
Tags: 123-11-5 synthesis path| 123-11-5 SDS| 123-11-5 COA| 123-11-5 purity| 123-11-5 application| 123-11-5 NMR| 123-11-5 COA| 123-11-5 structure
Precautionary Statements-General | |
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P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
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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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