Structure of 307951-53-7
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CAS No. : | 307951-53-7 |
Formula : | C8H7ClN2 |
M.W : | 166.61 |
SMILES Code : | CC1=CC2=C(N1)N=CC=C2Cl |
MDL No. : | MFCD12924600 |
InChI Key : | OFCAZVVESRXGRC-UHFFFAOYSA-N |
Pubchem ID : | 21081675 |
GHS Pictogram: | ![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.12 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 46.07 |
TPSA ? Topological Polar Surface Area: Calculated from | 28.68 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from | 1.8 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by | 2.34 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from | 2.52 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from | 1.9 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by | 3.12 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions | 2.34 |
Log S (ESOL):? ESOL: Topological method implemented from | -2.95 |
Solubility | 0.186 mg/ml ; 0.00112 mol/l |
Class? Solubility class: Log S scale | Soluble |
Log S (Ali)? Ali: Topological method implemented from | -2.58 |
Solubility | 0.437 mg/ml ; 0.00262 mol/l |
Class? Solubility class: Log S scale | Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by | -3.91 |
Solubility | 0.0207 mg/ml ; 0.000124 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) | 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 | -5.65 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) | 1.41 |
* 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 |
---|---|---|
77% | With N-ethyl-N,N-diisopropylamine; In 1-methyl-pyrrolidin-2-one; at 170℃; for 3h;Microwave irradiation; | Morpholine (1.0 g, 11 mmol) and N,N-diisopropylethylamine (2 mL) wereadded to a mixture of 4-chloro-2-methyl-IH-pyrrolo[2,3-b]pyridine (1.0 g, 6.0 mmol) in 1- methylpyrrolidin-2-one (15 mL). The reaction mixture was heated at 170 C for 3 hoursin a microwave reactor, then diluted with water (30 mL) and extracted with ethyl acetate (2 x 50 mL). The combined organic layers were washed with saturated aqueous sodium chloride solution (50 mL), dried over sodium sulfate, filtered, and concentrated in vacuo; chromatography on silica gel (Gradient: 0% to 50% ethyl acetate in petroleum ether) provided the product as a white solid. Yield: 1.0 g, 4.6 mmol, 77%. H NMR (400 MHz,DMSO-d6) oe 11.24 (brs, 1H), 7.86 (d, J=5.4 Hz, 1H), 6.38 (d, J=5.5 Hz, 1H), 6.15-6.17 (m, 1 H), 3.74-3.79 (m, 4H), 3.26-3.31 (m, 4H), 2.33 (br s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With palladium diacetate; potassium hydroxide; XPhos; In tert-butyl alcohol; at 100℃; for 2h; | A stirred mixture of <strong>[307951-53-7]4-chloro-2-methyl-1H-pyrrolo[2,3-b]pyridine</strong> (20 mg, 0.12 mmol), 4-methoxyaniline (44 mg, 0.36 mmol), palladium(II) acetate (0.54 mg, 0.0024 mmol), 2- dicyclohexylphosphino-2?,4?,6?-triisopropylbiphenyl (2.9 mg, 0.006 mmol) and potassiumhydroxide (40 mg, 0.72 mmol) in t-BuOH (0.5 mL) was heated at 100 C for 2 h, then allowed to cool to ambient temperature. The resulting mixture was added to water (1 mL) and extracted with EtOAc (3 x 2 mL). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography, eluting with a gradient of CH2C12:MeOH - 100:0 to 90:10, to give the title compound. MS: m/z = 254.1 (M +1). ?H NMR (400 MHz, CD3OD) oe 7.69 (d, 1H, J= 5.8 Hz), 7.21 (m, 2H), 6.93 (m, 2H), 6.44 (d, 1H, J 5.8 Hz), 6.16 (q, 1H, J 1.0 Hz), 3.80 (s, 3H), 2.39 (d, 3H, J= 1.0 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In methanol; at 20℃; for 3h; | General procedure: [Ru(mu-Cl)(eta6-p-cym)Cl]2 (0.1 mmol, 61.2 mg) was dissolved in methanol (5 mL) and left toreact with two molar equivalents of the corresponding naza. The reaction mixture was stirredat ambient temperature for 20 min (reactions with 5Braza and 5Faza), 2 h (reactions with aza,3Iaza and 3Claza) or 3 h (reactions with 2Me4Claza, 3Cl5Braza and 3I5Braza), until the yellow(for 2, 4 and 5), or light (for 8) or dark (for 1, 3, 6 and 7) orange product was formed. Theproducts (Fig 1) were isolated by filtration, washed with methanol (2 × 2 mL) and diethyl ether(3 × 5 mL) and dried under the infrared lamp (40C, 4 h). The yields were 60-80%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In methanol; at 20℃; | General procedure: The platinum(II) diiodido complexes 1±8 (Fig 1) were prepared using a slight modification ofthe recently reported protocol [21]. Briefly, 0.5 mmol (207.5 mg) of K2[PtCl4] was dissolved in5 mL of deionized water at 60 C and an excess of KI (415.0 mg; 2.5 mmol) was added to the red solution, which turned dark red over 10 min of stirring at 60 C. After cooling to ambienttemperature, 1.0 mmol of naza (118.1 mg for aza, 152.6 mg for 3Claza and 4Claza, 197.0 mg for3Braza, 4Braza 5Braza, 244.0 mg for 3Iaza and 166.6 mg for 2Me4Claza; Fig 1) dissolved in 5mL of methanol was poured in. The mixture was stirred overnight at ambient temperature andthe obtained yellow solid was removed by filtration and washed with deionized water (3 × 5mL), methanol (3 × 2 mL) and diethyl ether (3 × 5 mL). The products (yields ~90%) weredried under vacuum and stored in desiccator over silica gel. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With chloro(2-dicyclohexylphosphino-2?,4?,6?-triisopropyl-1,1?-biphenyl)[2-(2?-amino-1,1?-biphenyl)]palladium(II); caesium carbonate; In tetrahydrofuran; water; at 65℃; for 5h;Inert atmosphere; | A mixture of (S)-tert-butyl (2,4-dimethyl-l-(2-methyl-4-(4,4,5,5-tetramethyl- l,3,2-dioxaborolan-2- yl)phenoxy) pentan-2-yl)carbamate (prepared using the procedure described in Example 285) (0.070 g, 0.156 mmol), 4-chloro-2- methylpyrimidine (0.02 g, 0.156 mmol), and tripotassium phosphate (2M Solution) (0.5 mL, 1.00 mmol) in THF (2 mL) was purged with nitrogen fori 5 min. XPhos 2nd generation precatalyst (0.037 g, 0.047 mmol) was added and the mixture purged for a further 5 min. The reaction mixture was then stirred at 75 C for 2.5 h. The reaction mixture was cooled to room temperature and diluted with THF (15 mL) and filtered through diatomaceous earth (Celite). The bed was washed with excess of THF. The filtrate was concentrated under reduced pressure. The crude product was purified by silica gel chromatography (ethyl acetate and pet ether) to afford (S)-tert- butyl (2,4-dimethyl-l -(2-methyl-4-(2-methylpyrimidin-4-yl)phenoxy)pentan-2- yl)carbamate (0.018 g, 0.036 mmol, 23% yield) as a yellow oil. LCMS (ESI) m/e 414.4 [(M+H) +, calcd for C24H36N3O3, 414.26]; LC/MS retention time (method A2); to = 2.30 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44% | With chloro(2-dicyclohexylphosphino-2?,4?,6?-triisopropyl-1,1?-biphenyl)[2-(2?-amino-1,1?-biphenyl)]palladium(II); caesium carbonate; In tetrahydrofuran; water; at 65℃; for 4h;Inert atmosphere; | A mixture of 4-chloro-2-methyl-lH-pyrrolo[2,3-Z>]pyridine (0.028 g, 0.141 mmol), (S)-tert-bu y (2,4-dimethyl-l-(4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2- yl)-2-(trifluoromethyl)phenoxy)pentan-2-yl)carbamate (prepared as described in Example 215, Parts A and B) (0.071 g, 0.141 mmol), and CS2CO3 (0.069 g, 0.212 mmol) in THF (2 mL) and water (0.667 mL) was purged with nitrogen for 15 min. XPhos 2nd generation precatalyst (0.017 g, 0.021 mmol) was added and nitrogen gas was bubbled through reaction mixture for 5 min and stirred at 65 C for 4 h. The reaction mixture was cooled to room temperature and diluted with THF (10 mL) and filtered through diatomaceous earth (Celite). The bed was washed with excess THF. The filtrate was concentrated under reduced pressure. The crude product was purified by silica gel chromatography (ethyl acetate and pet ether) to afford (S)-tert- butyl (2,4-dimethyl-l-(4-(2-methyl-lH-pyrrolo[2,3- )]pyridin-4-yl)-2- (trifluoromethyl)phenoxy)pentan-2-yl)carbamate (0.032 g, 0.062 mmol, 44% yield) as a pale yellow oil. LCMS (ESI) m/e 506.2 [(M+H)+, calcd for C27H36F3N3O3, 506.26]; LC/MS retention time (Method Al); fa = 2.80 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With sodium hydroxide; In methanol; at 70℃; for 5h; | To a solution of 4-chloro-l-((4-ethylphenyl)sulfonyl)-2-methyl-lH- pyrrolo [2,3 -b] pyridine (0.2 g, 0.585 mmol) in MeOH (4 mL) was added 5M NaOH solution (0.585 mL, 2.93 mmol) at room temperature. The whole mixture was heated at 70 C for 5 h. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was diluted with ethyl acetate (15 mL) and water (10 mL). The organic layer was re-extracted with ethyl acetate (2 x 10 mL). The combined organics were dried and concentrated to afford 4-chloro-2- methyl-lH-pyrrolo[2,3-Z>]pyridine (0.1 g, 0.504 mmol, 86% yield) as a pale yellow solid. LCMS (ESI) m/e 167.2 [(M+H)+, calcd for C8H8C1N2 , 167.03]; LC/MS retention time (Method Al); fa = 1.82 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With sodium hydroxide; In N,N-dimethyl-formamide; at -10℃; for 4h; | At -10 C, to a solution of 4- chloro-2-methyl- 1 H-pyrrolo [2,3 -bjpyridine (338 mg, 2.03 minol) in N,N-dimethylfonnamide (10 mL) was added sodium hydroxide (240 mg, 6.00 minol). Then lodomethane (284 mg, 2.00 minol) was added and the resultingminxture was stirred for 4 h at -10 C. When the reaction was done, the reactionminxture was deluted by DCM (100 mL) and the resultingminxture was washed with water (30 mL x 3). The organic phase was washed with brine and dried over Na2SO4. The solvent was removed under reduced pressure and the residue was purified by flash chromatography eluting with EtOAc in petroleum ether (0% to 10% gradient) to yield 4-chloro-1,2-dimethyl-1H- pyrrolo[2,3-bjpyridine as yellow solid (300 mg, 82%). MS: m/z = 181.0 [M+Hj. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | To a 250 mL round bottom flask was added NaH (60% dispersion in mineral oil, 1.39 g, 34.8 mmol) as a solid. The flask was evacuated and backfilled with N2. DMF (25 mL) was added and the round bottom flask was placed into an ice/water bath and cooled to 3 ?C. A solution of 4-chloro-2-methyl-lH- pyrrolo[2,3-?]pyridine (4.07 g, 24.4 mmol) in DMF (34 mL) was then added slowly (over 45 minutes) via addition funnel and was stirred for 45 min. /?-Toluenesulfonyl chloride (5.75 g, 29.9 mmol) was dissolved into DMF (33 mL) and the resulting solution was added dropwise over 20 minutes. Reaction progress was monitored by LCMS analysis. NOTE: attempts to add additional quantities of TsCl did not push reaction conversion further. The reaction was poured slowly onto 500 mL ice water while stirring vigorously, which caused a precipitate to form. Next was added 1 M NaOH (35 mL) and the reaction was stirred for 1 h. The solids were collected by suction filtration. The solids were crushed to a fine powder and dried under vacuum for 1 day using high vacuum (100 mTorr) to afford the title compound (7.82 g, 95%) as a tan powder. MS (ESI): mass calcd. for C15H13CIN2O2S, 320.0; m/z found, 321.0 [M+H]<+>.<1>H NMR (500 MHz, CDCh): ? 8.25 (d, J = 5.3 Hz, 1H), 8.06 - 7.96 (m, 2H), 7.30 - 7.23 (m, 2H), 7.13 (d, J = 5.3 Hz, 1H), 6.42 - 6.37 (m, 1H), 2.74 (s, 3H), 2.36 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
3% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 90℃; for 2h; | 2-tert-Butoxy-4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-6-[2- (trifluoromethyl)-1 -piperidyl]pyridine (1 10 mg, 0.26 mmol), 4-chloro-2-methyl- 1 H-pyrrolo[2,3-b]pyridine (95 mg, 0.57 mmol), K2CO3 (89 mg, 0.64 mmol) and PdCl2(dppf) (14 mg, 0.02) were taken up in 1 ,4-dioxane and water and the mixture was stirred at 90 C for 2h. When cooled to rt EtOAc was added and the mixture filtered. The organic layer was separated, dried over MgSO4 and concentrated. The resulting residue was dissolved in DCM, TFA (0.1 1 ml, 1 .54 mmol) was added, the mixture stirred at rt for 30 min, concentrated and purified by preparative HPLC to give the product as a solid (3.4 mg, 3 %). 1H NMR (500 MHz, METHANOL-^) delta ppm 1 .62 - 1 .70 (m, 1 H), 1 .76 - 1 .94 (m, 4 H), 2.07 - 2.16 (m, 1 H), 2.51 (d, 3 H), 3.19 - 3.28 (m, 1 H), 3.85 - 4.06 (m, 1 H), 5.37 (br d, 1 H), 6.32 (d, 1 H), 6.36 (d, 1 H), 6.39 - 6.47 (m, 1 H), 7.17 (d, 1 H), 8.06 - 8.27 (m, 1 H). MS ES+ m/z 377 [M+H]+. |
Tags: 307951-53-7 synthesis path| 307951-53-7 SDS| 307951-53-7 COA| 307951-53-7 purity| 307951-53-7 application| 307951-53-7 NMR| 307951-53-7 COA| 307951-53-7 structure
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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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