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CAS No. : | 7752-72-9 |
Formula : | C5H5ClN2O |
M.W : | 144.56 |
SMILES Code : | O=C1NC=NC(C)=C1Cl |
MDL No. : | MFCD08234409 |
InChI Key : | YIDUVRHFPFLCLN-UHFFFAOYSA-N |
Pubchem ID : | 135512950 |
GHS Pictogram: | ![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.2 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 34.83 |
TPSA ? Topological Polar Surface Area: Calculated from | 45.75 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from | 1.09 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by | 0.5 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from | 0.73 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from | 0.38 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by | 2.17 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions | 0.97 |
Log S (ESOL):? ESOL: Topological method implemented from | -1.54 |
Solubility | 4.13 mg/ml ; 0.0285 mol/l |
Class? Solubility class: Log S scale | Very soluble |
Log S (Ali)? Ali: Topological method implemented from | -1.03 |
Solubility | 13.5 mg/ml ; 0.0932 mol/l |
Class? Solubility class: Log S scale | Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by | -2.54 |
Solubility | 0.418 mg/ml ; 0.00289 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 | Yes |
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 | -6.83 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 | 1.0 |
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 | 0.0 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) | 1.44 |
* 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 |
---|---|---|
0.7 g (22%) | Step A: Preparation of 5-Chloro-6-hydroxy-4-methylpyrimidine Under N2, a solution of ethyl 2-chloroacetoacetate (1.8 ml, d=1.15, 0.013 mol) in CHCl3 (50 ml) was added dropwise to a solution 4-methoxybenzamidine (3.9 g, 0.026 mol) in CHCl3 (100 ml). After stirring overnight, the reaction mixture was filtered and the filtrate was washed with dilute NaOH solution. The aqueous layer was extracted with CH2 Cl2 (3*) and the organic layer was dried, filtered and concentrated to dryness. The residue was chromatographed on silica gel and the product was eluted with 2% CH3 OH-CHCl3 (v/v) to yield 0.7 g (22%) of product m.p. 250-251 C. | |
(2) The compound prepared in reference example 3-(1) (5.0g, 45mmol) was dissolved in acetic acid (5ml), and chlorine gas generated by potassium permanganate (11g) and concentrated hydrochloric acid (70ml) was bubbled through the reaction mixture at or below 15 ØC. After the reaction mixture was stirred at room temperature for 1 hour, the crystal separated was collected by filtration, and dried to give 5-chloro-4-hydroxy-6-methylpyrimidine (6.8g). 1H-NMR(DMSO-d6) delta 2.33(3H, s), 8.08(1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
16.6 g (67.5%) | With sodium methylate; formamide; In methanol; | Example 11 5-Chloro-4-hydroxy-6-methylpyrimidine 25.9 g (0.17 mol) of methyl 3-amino-2-chloro-2-butenoate are reacted with 11.7 g (0.26 mol) of formamide and 51 ml of sodium methylate solution in 20 ml of methanol and worked up in analogy to Example 9 (reaction time 20 h). Yield: 16.6 g (67.5%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | 1) The Preparation of 4-hydroxyl-5-chloro-6-methylpyrimidine 8.80 g (0.16 mol) of CH3ONa in methanol was added slowly to a solution of 11.30 g (0.11 mol) of formimidamide in 50 mL of methanol at room temperature under stirring, the mixture was stirred for another 2 h after addition at room temperature. Followed by addition of 11.17 g (0.068 mol) of ethyl 2-chloro-3-oxobutanoate, the mixture was continued stirring for another 5-7 h at room temperature. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was concentrated under reduced pressure and pH was adjusted to 5-6 with HCl, and then filtered to afford orange-yellow solid, the water phase was extracted with ethyl acetate (3*50 ml), dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was dissolved to 50 ml of ethyl acetate, stand overnight to obtain 6.48 g as orange-yellow solid with yield of 66%, m.p, 181184 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88.5% | With trichlorophosphate; In toluene;Reflux; | 2) The Preparation of Intermediate 4,5-dichloro-6-methylpyrimidine 50 ml of POCl3 was added dropwise to a solution of 14.5 g (0.1 mol) of <strong>[7752-72-9]4-hydroxyl-5-chloro-6-methylpyrimidine</strong> in 50 mL of toluene, the mixture was refluxed for 5-7 h after addition. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was concentrated under reduced pressure to remove toluene and extra POCl3, and then poured into ice water. The water phase was extracted with ethyl acetate (3*50 ml), the organic phases were emerged, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was purified through silica column to give 14.43 g as yellow liquid with yield of 88.5%. |
88.5% | With trichlorophosphate; In toluene;Reflux; | The preparation of intermediate 4,5-dichloro-6-methylpyrimidine ;50ml of POCl3 was added dropwise to a solution of 14.5g ( 0.lmol ) of <strong>[7752-72-9]4-hydroxyl-5-chloro-6-methylpyrimidine</strong> in 50 mL of toluene, the mixture was refluxed for 5-7 hrs after addition. ;After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was concentrated under reduced pressure to remove toluene and extra POCl3, and then poured into ice water. ;The water phase was extracted with ethyl acetate (3x50mL), the organic phases were emerged, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was purified through silica column to give 14.43g as yellow liquid with yield of 88.5%. |
88.5% | With trichlorophosphate; In toluene;Reflux; Enzymatic reaction; | 2) Preparation of 4,5-dichloro-6-methylpyrimidineThe 14.5g (0.1mol) <strong>[7752-72-9]4-hydroxy-5-chloro-6-methylpyrimidine</strong> dissolved in 50ml of toluene, was added dropwise with stirring to the reaction flask 50ml of phosphorus oxychloride dropwise at reflux temperature the reaction completion 5-7 hours after, TLC monitored the reaction is complete. The toluene was evaporated under reduced pressure and an excess of phosphorus oxychloride, while stirring the reaction was poured into ice water, the aqueous phase was extracted with (3 × 50ml) and extracted with ethyl acetate, the combined organic phase was dried over anhydrous magnesium sulfate, filtered, desolvation . The residue was purified by column chromatography (eluent, ethyl acetate and petroleum ether (boiling range 60-90 ), the volume ratio of 1: 4) was isolated as a yellow liquid 14.43g, yield 88.5%. |
88.5% | With trichlorophosphate; In toluene; at 5 - 7℃;Reflux; | 14.5g (0.1mol) 4- hydroxy-5-chloro-6-methylpyrimidine dissolved in 50ml of toluene, was added dropwise with stirring to the reaction flask 50ml phosphorus oxychloride, after dropwise addition the reaction heated at reflux for 5-7 hours, TLC monitored after completion of the reaction. Toluene was evaporated under reduced pressure and excess phosphorus oxychloride, with stirring the reaction was poured into ice water, the aqueous phase was extracted with ethyl acetate (3 × 50ml), the combined organic phase was dried over anhydrous magnesium sulfate, filtered, and dissolved. The residue was purified by column chromatography (eluent, ethyl acetate and petroleum ether (boiling range 60-90 deg. C), the volume ratio of 1: 4) was isolated as a yellow liquid 14.43g, yield 88.5%. |
88.5% | With trichlorophosphate; In toluene;Reflux; | The 14.5g (0.1mol) 4- hydroxy-5-chloro-6-methylpyrimidine dissolved in 50ml of toluene, was added dropwise with stirring to the reaction flask 50ml of phosphorus oxychloride dropwise at reflux temperature the reaction completion 5-7 hours . After completion of the reaction was monitored by TLC, toluene was distilled off under reduced pressure and an excess of phosphorus oxychloride, while stirring the reaction was poured into ice water, the aqueous phase was extracted with (3 × 50ml) and extracted with ethyl acetate, the combined organic phase was dried over anhydrous magnesium dried, filtered, removing solvent. The residue was purified by column chromatography (eluent, ethyl acetate and petroleum ether, the volume ratio of 1: 5) was isolated yellow liquid 14.43 g, 88.5% yield. |
88.5% | With trichlorophosphate; In toluene;Reflux; | 50 ml of POCl3 was added dropwise to a solution of 14.5 g (0.1 mol) of <strong>[7752-72-9]4-hydroxyl-5-chloro-6-methylpyrimidine</strong> in 50 mL of toluene, the mixture was refluxed for 5-7 h after addition. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was concentrated under reduced pressure to remove toluene and extra POCl3, and then poured into ice water. The water phase was extracted with ethyl acetate (3*50 mL), the organic phases were emerged, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was purified through silica column (ethyl acetate/petroleum ether=1:5, as an eluent) to give 14.43 g as yellow liquid with yield of 88.5%. |
88.5% | With trichlorophosphate; In toluene;Reflux; | Dissolve 14.45 g (0.1 mol) of <strong>[7752-72-9]4-hydroxy-5-chloro-6-methylpyrimidine</strong> in 50 ml of toluene and stir it under anti-flask50 ml of phosphorus oxychloride was added dropwise, and the reaction was heated to reflux for 5-7 hours. TLC was monitored after the reaction was completed. Vacuum distillation of toluene andThe amount of phosphorous oxychloride was poured into ice water with stirring, the aqueous phase was extracted with (3×50 ml) ethyl acetate, and the organic phases were combined.Anhydrous magnesium sulfate drying and desolventization. Chromatographic separation of the yellow liquid 14.43g, the yield of 88.5%. |
88.5% | With trichlorophosphate; In toluene;Reflux; | Dissolve 14.5 g (0.1 mol) of <strong>[7752-72-9]4-hydroxy-5-chloro-6-methylpyrimidine</strong> in 50 ml of toluene, add 50 ml ofphosphorus oxychloride to the reaction flask with stirring, and then heat up to reflux for 5-7 hours. After TLC monitoring was completed, toluene and excess phosphorus oxychloride were distilled off underreduced pressure. The reaction was poured into ice water with stirring. The aqueous phase was extracted with(3×50 ml) ethyl acetate, and the organic phases were combined and dried over anhydrous magnesium sulfate.Dry, filter, and dissolve. The residue was purified by column chromatography (eluent: ethyl acetate and petroleum ether, 1 : 5 in volume) to give 14.43 g of a yellow liquid, yield 88.5%. |
88.5% | With trichlorophosphate; In toluene;Reflux; | 50 ml of POCl3 was added dropwise to a solution of 14.5 g (0.1 mol) of <strong>[7752-72-9]4-hydroxyl-5-chloro-6-methylpyrimidine</strong> in 50 mL of toluene, the mixture was refluxed for 5-7 h after addition. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was concentrated under reduced pressure to remove toluene and extra POCl3, and then poured into ice water. The water phase was extracted with ethyl acetate (3*50 mL), the organic phases were merged, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was purified through silica column (ethyl acetate/petroleum ether=1:5, as an eluent) to give14.43 g as yellow liquid with yield of 88.5%. |
88.5% | With trichlorophosphate; In toluene;Reflux; | 14.5 g (0.1 mol) of <strong>[7752-72-9]4-hydroxy-5-chloro-6-methylpyrimidine</strong> was dissolved in 50 ml of toluene solution.50 ml of phosphorus oxychloride was added dropwise to the reaction flask under stirring, and the mixture was heated under reflux for 5-7 hours.After the TLC monitoring reaction was completed, toluene and excess phosphorus oxychloride were distilled off under reduced pressure, and the reactant was poured into ice water with stirring.The aqueous phase was extracted with ethyl acetate (3 × 50ml), the organic phases were combined, dried over anhydrous magnesium sulfate, filtered, desolventized.Residue column chromatography (eluent is ethyl acetate and petroleum ether,Volume ratio of 1: 5) to give yellow liquid was isolated 14.43g, yield 88.5%. |
88.5% | With trichlorophosphate; In toluene;Reflux; | Dissolve 14.5g (0.1mol) <strong>[7752-72-9]4-hydroxy-5-chloro-6-methylpyrimidine</strong> in 50ml toluene solution,Under stirring, 50ml of phosphorus oxychloride was dropped into the reaction bottle, and the temperature was raised and the reaction was refluxed for 5-7 hours.After the reaction was monitored by TLC, toluene and excess phosphorus oxychloride were distilled off under reduced pressure.The reaction was poured into ice water with stirring, the aqueous phase was extracted with (3 × 50 ml) ethyl acetate, the organic phases were combined, dried over anhydrous magnesium sulfate, filtered and desolvated.The residue was separated by column chromatography (eluent was ethyl acetate and petroleum ether, volume ratio was 1: 5) to obtain a yellow liquid 14.43g, yield 88.5%. |
88.5% | With trichlorophosphate; In toluene;Reflux; | Dissolve 14.5g (0.1mol) of <strong>[7752-72-9]4-hydroxy-5-chloro-6-methylpyrimidine</strong> in 50ml of toluene solution, drop 50ml of phosphorus oxychloride into the reverse bottle with stirring, and after heating up, reflux and react for 5-7 hours , After the reaction was monitored by TLC. Toluene and excess phosphorus oxychloride were distilled off under reduced pressure, the reaction was poured into ice water with stirring, the aqueous phase was extracted with (3 × 50 ml) ethyl acetate, the organic phases were combined, dried over anhydrous magnesium sulfate, filtered and desolvated . Column chromatography of the residue (eluent is ethyl acetate and petroleum ether (boiling range 60-90 C), volume ratio is 1: 5) to obtain a yellow liquid 14.43g, yield 88.5%. |
With trichlorophosphate; In toluene;Reflux; | General procedure: POCl3 (100 mL) was added dropwise to a solution of M-2 (0.36 mol)in toluene (150 mL), the mixture was refluxed for 3-5 h. The reactionmixture was concentrated under reduced pressure to remove tolueneand extra POCl3, and then poured into ice water. The water phase wasextracted with ethyl acetate (3 × 50 mL), the emerged organic phasewas successively washed with saturated sodium bicarbonate, dried overanhydrous magnesium sulfate, filtered and then concentrated underreduced pressure. The residue was purified through silica column togive M-3 as yellow liquid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | The preparation of 4-hydroxyl-5-chloro-6-methylpyrimidine ;8.80g (0.16mol) of CH3ONa in methanol was added slowly to a solution of 11.30g (0.11mol of formimidamide in 50 mL of methanol at room temperature under stirring, the mixture was stirred for another 2 hrs after addition at room temperature. ;Followed by addition of 11.17g ( 0.068mol ) of ethyl 2-chloro-3-oxobutanoate, the mixture was continued stirring for another 5-7 hrs at room temperature. ;After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was concentrated under reduced pressure and pH was adjusted to 5-6 with HCl, and then filtered to afford orange-yellow soilid, the water phase was extracted with ethyl acetate (3x50mL), dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. ;The residue was dissolved to 50ml of ethyl acetate, stand overnight to obtain 6.48g as orange-yellow soilid with yield of 66%. m.p. 181~184C. | |
66% | 1) Preparation of 4-hydroxy-5-chloro-6-methylpyrimidineStirring at room temperature to a solution of methanol 50ml 11.30g (0.11mol) of formamidine acetate was added slowly dropwise 8.80g (0.16mol) of sodium methoxide methanol solution was dropwise completed stirring was continued at room temperature 2h. To the above solution was then added dropwise 11.17g (0.068mol) of 2-chloroacetyl ethyl acetate, the reaction was stirred for 5-7 hours at room temperature continued, monitored by TLC after completion of the reaction, the solvent was distilled off under reduced pressure, adjusted to pH = 5 with hydrochloric acid 1-6, orange solid was suction filtered, the aqueous phase with (3 × 50ml) and extracted with ethyl acetate, dried over anhydrous magnesium sulfate, filtered, and desolvation. The residue was dissolved in 50ml of ethyl acetate and allowed to stand overnight, and filtered to give an orange solid 6.48g. Yield 66%, m.p. 181 ~ 184 . | |
66% | With stirring at room temperature, to 11.30g (0.11mol) of formamidine acetate in 50ml of methanol was slowly added dropwise 8.80g (0.16mol) of methanol solution of sodium methoxide, after dropwise addition, at room temperature and stirring was continued for 2h. To the above solution was then added dropwise 11.17g (0.068mol) of intermediate ethyl 2-chloroacetoacetate, continued stirring for 5-7 hours at room temperature. After completion of the reaction monitored by TLC, the solvent was distilled off under reduced pressure, adjusted with hydrochloric acid pH = 5 ~ 6, orange solid was suction filtered, the aqueous phase was extracted with ethyl acetate (3 × 50ml), dried over anhydrous magnesium sulfate, filtered, removing solvent. The residue was dissolved in 50ml of ethyl acetate and allowed to stand overnight, and filtered to give an orange solid 6.48g. Yield 66%, m.p. 181 ~ 184 deg. C. |
66% | Stirring at room temperature to a solution of methanol 50ml 11.30g (0.11mol) of formamidine acetate was added slowly dropwise 8.80g (0.16mol) of sodium methoxide in methanol, stirring was continued at room temperature completion of dropwise 2h. Then added dropwise 11.17g (0.068mol) ethyl 2-chloroacetoacetate intermediate to the above solution, the reaction was stirred for 5-7 hours at room temperature continued. After completion of the reaction was monitored by TLC, the solvent was distilled off under reduced pressure, adjusted to pH = 5 with hydrochloric acid to 6, orange solid was suction filtered, the aqueous phase with (3 × 50ml) and extracted with ethyl acetate, dried over anhydrous magnesium sulfate, filtered off solution. The residue was dissolved in 50ml of ethyl acetate and allowed to stand overnight, and filtered to give an orange solid 6.48g. Yield 66% | |
66% | To a solution of 11.30 g (0.11 mol) methylhydrazine acetate in 50 ml of methanol was slowly added dropwise 8.80 g with stirring at room temperature.(0.16 mol) of sodium methoxide in methanol, and the mixture was stirred at room temperature for 2 h. Then 11.17 g (0.068 mol) was added dropwise to the above solution.Ethyl 2-chloro-acetoacetate was stirred at room temperature for 5-7 hours. After TLC monitoring was completed, the solvent was distilled off under reduced pressure and salt was used.The pH was adjusted to 5-6, and the orange solid was filtered by suction. The aqueous phase was extracted with ethyl acetate (3×50 ml), dried over anhydrous magnesium sulfate, and dissolved.The combined product was dissolved in 50 ml of ethyl acetate, allowed to stand overnight and filtered to give 6.48 g of an orange-yellow solid. Yield 66.0% | |
66% | A solution of 8.80 g (0.16 mol) of sodium methoxide in methanol was slowly added dropwise to a solution of 11.30 g (0.11 mol) of methylacetoacetate in 50 ml of methanol at room temperature with stirring, and the mixturewas stirred at room temperature for 2 hours. Then, 11.17 g (0.068 mol) of the intermediate 2-chloroacetoacetic acid ethylacetate was added dropwise to theabove solution, and the reaction was continued for 5-7 hours while stirring at room temperature. After the TLCmonitoring reaction was completed, the solvent was evaporated under reduced pressure, and the pH wasadjusted to 5-6 with hydrochloric acid. The orange solid was collected by suction filtration, and the aqueousphase was extracted with ethyl acetate (3×50 ml), dried over anhydrous magnesium sulfate, filtered and shaken.Dissolved. The residue was dissolved in 50 ml of ethyl acetate, allowed to stand overnight and filtered to give 6.48g of an orange-yellow solid. The yield of 66%. | |
66% | 10343] A solution of 8.80 g (0.16 mol) of CH3ONa in methanol was added slowly to a solution of 11.30 g (0.11 mol) of formimidamideacetate in 50 mL of methanol at room temperature under stirring, the mixture was stirred for another 2 h after addition at room temperature. Followed by addition of 11.17 g (0.068 mol) of ethyl 2-chloro-3-oxobu- tanoate, the mixture was continued stirring for another 5-7 h at room temperature. Afier the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was concentrated under reduced pressure and pH was adjusted to 5-6 with HC1, and then filtered to afford orangeyellow solid, the water phase was extracted with ethyl acetate (3x50 mL), dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was dissolved to 50 ml of ethyl acetate, stand overnight to obtain 6.48 g as orange-yellow solid with yield of 66%. m.p. 181-184 C. | |
66% | To a solution of 11.30 g (0.11 mol) of formamidine acetate in 50 ml of methanol, a solution of 8.80 g (0.16 mol) of sodium methoxide in methanol was slowly added dropwise with stirring at room temperature.Stirring was continued for 2 h at room temperature.Then, 11.17 g (0.068 mol) of an intermediate ethyl 2-chloroacetoacetate was added dropwise to the above solution, and the reaction was further stirred at room temperature for 5-7 hours.After the TLC monitoring reaction was completed, the solvent was evaporated under reduced pressure, and the mixture was adjusted to pH 5 to 6 with hydrochloric acid, and filtered to give an orange-yellow solid.The aqueous phase was extracted with (3 × 50ml) of ethyl acetate, dried over anhydrous magnesium sulfate, filtered, desolventized.The residue was dissolved in 50ml of ethyl acetate, allowed to stand overnight, and filtered to give an orange-yellow solid 6.48g. Yield 66%, | |
66% | To a solution of 11.30 g (0.11 mol) formamidine acetate in 50 ml of methanol under stirring at room temperature, 8.80 g (0.16 mol) of sodium methoxide in methanol was slowly added dropwise, and stirring was continued at room temperature for 2 h.Then, 11.17 g (0.068 mol) of intermediate ethyl 2-chloroacetoacetate was added dropwise to the above solution, and the reaction was continued to be stirred at room temperature for 5-7 hours.After the reaction was monitored by TLC, the solvent was distilled off under reduced pressure, and the pH was adjusted to 5-6 with hydrochloric acid.Filtration with suction yielded an orange-yellow solid, and the aqueous phase was extracted with (3 × 50 ml) ethyl acetate, dried over anhydrous magnesium sulfate, filtered and desolvated.The residue was dissolved in 50 ml of ethyl acetate, left overnight, and filtered to obtain 6.48 g of orange solid. The yield is 66%, | |
66% | To a solution of 11.30 g (0.11 mol) formamidine acetate in 50 ml of methanol under stirring at room temperature, 8.80 g (0.16 mol) of sodium methoxide in methanol was slowly added dropwise, and stirring was continued at room temperature for 2 h. Then, 11.17g (0.068mol) of intermediate ethyl 2-chloroacetoacetate was added dropwise to the above solution, and the reaction was stirred at room temperature for 5-7 hours. After the reaction was monitored by TLC, the solvent was distilled off under reduced pressure, and the pH was adjusted to 5 with hydrochloric acid. 6, suction filtration to obtain orange-yellow solid, the aqueous phase was extracted with (3 × 50ml) ethyl acetate, dried over anhydrous magnesium sulfate, filtered and desolvated. The residue was dissolved in 50 ml of ethyl acetate, left overnight, and filtered to obtain 6.48 g of orange solid. 66% yield | |
With sodium methylate; In methanol; at 5 - 20℃; | General procedure: A solution of formamidine acetate (0.70 mol) in methanol (150 mL)was stirred at 5-10 C, and then CH3ONa (1.20 mol) in methanol(150 mL) newly prepared was added slowly under stirring, followed byaddition of M-1 (0.50 mol) in methanol (100 mL). The mixture wascontinued stirring for another 3-4 h at room temperature and thenconcentrated under reduced pressure. The residue was adjusted to pH5-6 with diluted HCl, the precipitated solid was filtered to afford M-2 asa white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70.6% | With potassium carbonate; In N,N-dimethyl-formamide; at 100℃; | Take 0.15g (0.001mol) 4- hydroxy-5-chloro-6-methylpyrimidine, 0.21g (0.001mol) 4- chloro-1- (4-methylphenyl) lH-pyrazole, 0.14 g (0.001mol) of potassium carbonate in 50ml single neck flask, 10mlN, N- dimethylformamide as a solvent, was heated to 100 deg.] C, the reaction 4-10 hours, monitored by TLC after completion of the reaction, the solvent was distilled off under reduced pressure, was added ( 3 × 50ml) and extracted with ethyl acetate, the organic phase was washed with saturated brine 50ml, after solvent removal the residue by column chromatography (eluent, ethyl acetate and petroleum ether, the volume ratio of 1: 2) to give a white solid 0.22g yield 70.6% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With sodium methylate; In methanol; at 20℃; | A solution of 8.80 g (0.16 mol) of CH3ONa in methanol was added slowly to a solution of 11.30 g (0.11 mol) of formimidamide acetate in 50 mL of methanol at room temperature under stirring, the mixture was stirred for another 2 h after addition at room temperature. Followed by addition of 11.17 g (0.068 mol) of ethyl 2-chloro-3-oxobutanoate, the mixture was continued stirring for another 5-7 h at room temperature. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was concentrated under reduced pressure and pH was adjusted to 5-6 with HCl, and then filtered to afford orange-yellow solid, the water phase was extracted with ethyl acetate (3×50 mL), dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was dissolved to 50 ml of ethyl acetate, stand overnight to obtain 6.48 g as orange-yellow solid with yield of 66%. m.p. 181184 C. |
Tags: 7752-72-9 synthesis path| 7752-72-9 SDS| 7752-72-9 COA| 7752-72-9 purity| 7752-72-9 application| 7752-72-9 NMR| 7752-72-9 COA| 7752-72-9 structure
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6,7-Dichloroquinazolin-4(3H)-one
Similarity: 0.61
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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