Structure of 22900-83-0
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CAS No. : | 22900-83-0 |
Formula : | C7H8BrNO2S |
M.W : | 250.11 |
SMILES Code : | O=C(C1=C(C)N=C(Br)S1)OCC |
MDL No. : | MFCD03791227 |
InChI Key : | CFBIOWPDDZPIDP-UHFFFAOYSA-N |
Pubchem ID : | 2824057 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P301+P312-P302+P352-P304+P340-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.43 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 50.87 |
TPSA ? Topological Polar Surface Area: Calculated from |
67.43 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.58 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.93 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.39 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.13 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.34 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.48 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.35 |
Solubility | 0.113 mg/ml ; 0.00045 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-4.01 |
Solubility | 0.0246 mg/ml ; 0.0000982 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.02 |
Solubility | 0.239 mg/ml ; 0.000955 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) |
Yes |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
Yes |
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 |
-5.75 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 |
0.0 |
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<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.77 |
* 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 |
---|---|---|
87% | With nitrous acid isobutyl ester; trimethylsilyl bromide; In ethyl acetate; acetonitrile; at 0 - 20℃; for 24h; | TO A SOLUTION OF 2-METHYL-1-NITROSOOXY-PROPANE (28.2 ML, 2.1 EQ. ) IN CH3CN (700 ML) COOLED TO 0XB0;C WAS ADDED DROPWISE BROMO-TRIMETHYL-SILANE (32 ML, 2.1 EQ. ). THE] resulting mixture was maintained at [0XB0;C.] A solution of the available 2-amino-4- methyl-thiazole-5-carboxylic acid ethyl ester (18.6 g, 0.1 mol) in CH3CN/AcOEt 75/25 was added dropwise and the reaction mixture was maintained at [0XB0;C.] The mixture was stirred for 24 hours at rt. The solvent was evaporated and water was added. The product was extracted with AcOEt, dried over [NA2SO4,] filtered and evaporated. The title compound was obtained as a yellow solid (21.74 g, 87 [MMOL)] in 87% yield after purification by flash chromatography using DCM as eluent ; GC/MS: [M'C7H8BRNO2S] 250. |
87% | A solution of 2-methyl-1-nitrosooxy-propane (28.2 ml, 2.1 eq.) in CH3CN (700 ml) was cooled to 0C and bromo-trimethyl-silane (32 ml, 2.1 eq.) was added dropwise over 20 min. A solution of the available 2-amino-4-methyl-thiazole-5-carboxylic acid ethyl ester (18.6 g, 0.1 mot) in a mixture CH3CN/EtOAc : 75/25 heated to 55C was added dropwise over 45 min. During the addition the reaction was maintained at 0C and then allowed to warm to rt and stirred for 2 hours. After evaporation, the product was extracted with AcOEt, washed with water, dried over Na2SO4, filtered and evaporated. The title compound was obtained as a yellow solid (21.74 g, 86.96 mmol) in a 87% yield; GC/MS : M+ C7H6BrNO2S 250. | |
85% | With nitrous acid isobutyl ester; trimethylsilyl bromide; In ethyl acetate; acetonitrile; at 0 - 20℃; for 2.75h; | A solution of 2-methyl-1-nitrosooxypropane (20 [ML,] 2 eq) in CH3CN (700 mL) was [COOLED TO 0C AND BROMO-TRIMETHYL-SILANE (20 ML, 2 EQ. ) WAS ADDED DROPWISE OVER 20] min. The available 2-amino-4-methyl-thiazole-5-carboxylic acid ethyl ester (14.0 g, 75.2 [MMOL)] in a mixture of CH3CN/EtOAc [(75/25)] at [55C] was added dropwise over 45 min. During the addition the reaction was maintained at [0C.] After return at rt, the mixture was stirred for 2 hours. After evaporation, the product was extracted with DCM, washed with water, dried over [NA2SO4,] filtered and evaporated off. The title compound was obtained as a pale orange solid (16.06 g, 75.2 [MMOL)] in a 85% yield ; GC/MS: [M+ C7H8BRNO2S] 250 |
83% | A solution of copper(II) bromide (3.6 g, 16.11 mmol) and n-amyl nitrite (1.07 mL, 8.06 mmol) in acetonitrile (22 mL) was heated to 60C, and a solution of ethyl 2-amino-4-methyl-1,3-thiazole-5-carboxylate (1.0 g, 5.37 mmol) in acetonitrile (30 mL) was added dropwise thereto. The mixture was stirred for 4 hr at same temperature. The reaction mixture was allowed to cool to room temperature, and added into ice-cooled 1N aqueous sodium hydroxide solution. The mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate= 95:5→85:15) to give the title compound (1.1 g, 83%). 1H-NMR (CDCl3) δ : 1.37 (3 H, t, J = 7.1 Hz), 2.72 (3 H, s), 4.33 (2 H, q, J = 7.1 Hz). | |
76% | With tert.-butylnitrite; copper(ll) bromide; In acetonitrile; at 0℃; for 4h; | To a stirred solution of Intermediate 6 (0.53 g, 2.85 mmol) in MeCN (6 mL) at00C was added CuBr2 (0.70 g, 3.13 mmol) followed by dropwise addition of tert-buty nitrite (0.44 mL, 3.70 mmol). After stirring at 00C for 4 h, the reaction mixture was concentrated in vacuo to give a black oil. Purification by column chromatography (SiO2, 0-50% EtOAc/hexanes) gave the title compound (0.54 g, 76%) as a yellow solid. 6H (CDCl3) 4.33 (2H, q, J 7.0 Hz), 2.71 (3H, s), 1.36 (3H, t, J 7.2 Hz). MS (ES+) 252.0 (M+H)+. |
62% | With potassium bromide; copper(I) bromide; sodium nitrite; In water; at 60℃; for 1h; | Compound 3 (1 mmol) in HBr (3 mL) was added to cold aqueous solution of CuBr (1 mmol) and KBr(0.2 mmol) followed by dropwise addition of preliminary cooled aqueous solution of NaNO2(10 mL) for 1 h. The reaction mixture was stirred at 60C for 2 h. The reaction progress was monitored byTLC until the starting material completely disappeared.The reaction mixture was diluted with water,the obtained precipitate was filtered off to give ethyl 2-bromo-4-methylthiazole-5-carboxylate 4 as off-whitesolid in 62% yield. 1H NMR spectrum (CDCl3), δ,ppm: 4.28 q (2H), 2.81 s (3H), 1.33 t (3H). Massspectrum (ESI-MS): m/z 251 [M + H]+. |
59% | With copper(I) bromide; isopentyl nitrite; In acetonitrile; at 80℃; for 4h; | To a suspension of ethyl 2-amino-4-methylthiazole-5-carboxylate (1 g, 5.36 mmol, 1 eq) and CuBr2 (1.19 g, 5.36 mol, 1 eq) in acetonitrile (25 mL) was added isoamyl nitrite (2.16 mL, 16.08 mmol, 3 eq) dropwise at 25 C, and the reaction mixture was stirred at 80C for 4 h. The resulting reaction mixture was gradually cooled to 25 C and concentrated under reduced pressure to remove excess isoamyl nitrite and acetonitrile. The residue obtained was partitioned between water (250 mL) and ethyl acetate (250 mL), and the organic layer was separated, dried over sodium sulfate and concentrated under reduced pressure to obtain the crude compound as a brownish solid. The crude product obtained was purified by silica gel (23 0-400) column chromatography (10% ethyl acetate in hexane) to obtain ethyl 2-bromo-4-methylthiazole- 5-carboxylate (800 mg, 59%) as a yellow solid. |
With tert.-butylnitrite; copper(ll) bromide; In acetonitrile; at 60℃; for 1h; | Preparation of ethyl 2-bromo-4-methyithiazole-5-carboxylate (compound B: L=bromo: R=ethyl) To a solution of CuBr2 (75 gms/0.335 moles) in 750 ml acetonitrile was added t-butyl nitrite (28.6 gms/0.277 moles). The resultant mixture was heated to 60C and ethyl 2- amino-4-methylthiazole-5-carboxylate (35.0 gms/0.188moles) was further added in lots. The reaction mass was stirred for 1 hour at 60C. After completion of reaction, the reaction mass was cooled to 25C and about 150 ml water was added. The reaction mass was neutralized using 2N NaOH and extracted in ethyl acetate (300 ml). The organic layer was washed with water until a neutral pH. The separated organic layer was treated with charcoal. After drying the organic layer over anhydrous sodium sulphate, a clear filtrate was distilled off and 17.1 gms of the titled compound was obtained after drying at 40-45C as an off-white colored solid. Efficiency: 36% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 100℃; for 16h; | To a solution of 2-bromo-4-methyl-thiazole-5-carboxylic acid ethyl ester (2.0 g, 7.99 mmol) in toluene (60 mL), water (20 mL) and ethanol (20 mL) was added IH- pyrazole-5-boronic acid (1.79 g, 15.99 mmol), Pd(PPh3^ (0.92 g, 0.80 mmol), and <n="82"/>50352potassium carbonate (3.30 g, 23.98 mmol). The resulting mixture was degassed three times and heated to 100 0C for 16 hr. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (200 mL) and washed with brine (2 x 100 mL). The organic phase was dried (Na2SO4) and evaporated. The residue was purified by flash column chromatography (hexanes:ethyl acetate, 1 : 1) to provide 4-methyl-2-(2H-pyrazol- 3-yl)-thiazole-5-carboxylic acid ethyl ester (1.5 g, 83percent yield) as a yellow solid. MS (M+eta)+ = 238; R, = 1.2 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With trimethylsilyl bromide; In ethyl acetate; acetonitrile; at 0 - 20℃; | [2-BROMO-4-METHYL-THIAZOLE-5-CARBOXVLIC] acid ethyl ester To a solution of 3-methyl-1-nitrosooxy-butane (19.8 mL, 2.1 eq) in acetonitrile (700 mL) was added at [0XB0;C] trimethylsillyl bromide (19.6 mL, 2.1 eq) and the mixture was stirred at [0XB0;C] for 20 min. A solution of 2-amino-4-methyl-thiazole-5-carboxylic acid ethyl ester (14.0 g, 1.0 eq) in acetonitrile/EtOAc : 75/25 (700 mL) was added slowly at [0XB0;C.] After stirring overnight at rt, the reaction mixture was evaporated and purified by flash chromatography to give the title compound (13.2 g, 0. [051MOL)] as an orange solid in a 70% yield ; GC/MS: [M C7H8BRNO2S] 250;'H NMR [(CDC13,] 300 MHz) 5 4.32 (q, 2H), 2.69 (s, 3H), 1.34 (t, 3H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72.6% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 2-methyltetrahydrofuran; water; at 100℃;Inert atmosphere; | The title compound of this step was prepared by the method described in Example 7, Step 1, namely, 2-(4-Boc-piperazin-1-yl)pyrimidine-5-boronic acid pinacol ester (1.50 g, 3.84 mmol), ethyl 2-bromo-4-methylthiazole-5-formate (1.15 g, 4.61 mmol), cesium carbonate (3.13 g, 9.60 mmol) and [1,1?-bis(diphenylphosphino)ferrocene]palladium dichloride (II) (141 mg, 0.19 mmol) were added to a mixed solvent of 2-methyltetrahydrofuran (15 mL) and water (3 mL), the mixture was heated to 100 C and reacted overnight under N2. The residue was further purified by a silica gel column chromatography (dichloromethane/methanol (v/v) = 60/1) to give the title compound as a faint yellow solid (1.21 g, 72.6%).MS (ESI, pos. ion) m/z: 434.25 [M+Hfb;?HNMR (600 MHz, DMSO-d6) (ppm): 8.84 (s, 2H), 4.27 (q, J= 7.1 Hz, 2H), 3.913.79 (m, 4H), 3.43 (dd, J= 14.7, 10.3 Hz, 4H), 2.59 (s, 3H), 1.45 (s, 9H), 1.30 (t, J= 7.1 Hz, 3H). |
72.6% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 2-methyltetrahydrofuran; water; at 100℃;Inert atmosphere; | The title compound of this step is prepared by the method described in the first step of Example 7,2-(4-Boc-piperazin-1-yl)pyrimidine-5-boronic acid pinacol ester (1.50 g, 3.84 mmol),Ethyl 2-bromo-4-methylthiazole-5-carboxylate (1.15 g, 4.61 mmol) and cesium carbonate (3.13 g, 9.60 mmol) and[1,1'-bis(diphenylphosphino)ferrocene]palladium(II) chloride (141 mg, 0.19 mmol) in 2-methyltetrahydrofuran (15 mL)A mixed solvent of water (3 mL) was prepared by reacting at 100 C overnight under a nitrogen atmosphere.The obtained crude product was further purified by silica gel chromatography (dichloromethane:methanol (V:V)=60:1) to give the title compound(light yellow solid, 1.21 g, 72.6%). |
Tags: 22900-83-0 synthesis path| 22900-83-0 SDS| 22900-83-0 COA| 22900-83-0 purity| 22900-83-0 application| 22900-83-0 NMR| 22900-83-0 COA| 22900-83-0 structure
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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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