Structure of 5-Bromo-1-methyl-1H-indazole
CAS No.: 465529-57-1
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CAS No. : | 465529-57-1 |
Formula : | C8H7BrN2 |
M.W : | 211.06 |
SMILES Code : | CN1N=CC2=C1C=CC(Br)=C2 |
MDL No. : | MFCD09878568 |
InChI Key : | RMCHMXPTUMFFBZ-UHFFFAOYSA-N |
Pubchem ID : | 22558725 |
GHS Pictogram: | ![]() |
Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-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 | 0.0 |
Molar Refractivity | 48.7 |
TPSA ? Topological Polar Surface Area: Calculated from | 17.82 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from | 2.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by | 2.26 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from | 2.34 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from | 2.19 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by | 2.11 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions | 2.18 |
Log S (ESOL):? ESOL: Topological method implemented from | -3.18 |
Solubility | 0.14 mg/ml ; 0.000664 mol/l |
Class? Solubility class: Log S scale | Soluble |
Log S (Ali)? Ali: Topological method implemented from | -2.27 |
Solubility | 1.13 mg/ml ; 0.00536 mol/l |
Class? Solubility class: Log S scale | Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by | -3.33 |
Solubility | 0.0985 mg/ml ; 0.000467 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 | -5.98 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<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) | 1.54 |
* 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 |
---|---|---|
36%; 52% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium hydride; In tetrahydrofuran; at 20℃; for 3h; | The A14-1 (590mg, 2.99mmol) was dissolved in tetrahydrofuran (10mL), was added NaH in the case of an ice bath with stirring (180mg80%, 6.00mmol),After stirring for 30 minutes was added CH3I (468mg, 3.30mmol), stirring was continued for 3 hours, raised to room temperature, water (20 mL), ethyl acetate (20mL × 3)Extraction, the organic phase was washed with saturated brine (50mL × 3), dried over anhydrous sodium sulfate, and spin dry solvent, the residue was purified by column chromatography (petroleum ether: ethyl acetate= 10:1-3:1) to give A14-2 (230mg, 36%) and A14-3 (330mg, 52%).A14-2: off-white solid. 1HNMR (400MHz, DMSO) delta8.33 (s, 1H), 7.96-7.95 (m, 1H), 7.57 (d, J = 9.2Hz,1H), 7.31-7.28 (m, 1H), 4.16 (s, 3H).A14-3: white solid. |
29%; 42.5% | 5-Bromo-1-methyl-1 H-indazole (ii) and 5-Bromo-2-methyl-2H-indazole (iii)To a solution of 5-bromo-1 H-indazole (0.19 g, 0.94 mmol) in 3 mL THF at 0 0C was added NaH (0.04 g, 1.03 mmol). The reaction solution was stirred at this temperature for 1 hour before methyl iodide (0.09 mL, 1.41 mmol) was added at 0 0C. The reaction was allowed to warm to room temperature slowly and stirred for 2 hours, quenched with water and concentrated in vacuo. The residue was diluted with water and extracted with DCM twice. The organic layers were combined, dried over Na2SO4 and concentrated. The crude product was purified by flash chromatography (hexane:EtOAc = 10:1 ) to give the title compound ii (88.7 mg, 42.5 %) and iii (60.9 mg, 29 %) as two white solids, ii: 1H-NMR (400MHz, DMSO- Cf6) delta ppm 8.02 (d, 1 H), 7.99 (d, 1 H), 7.64 (d, 1 H), 7.50 (dd, 1 H), 4.04 (s, 3H). LCMS(method A): [MH]+ = 21 1/213, tR = 5.19 min. iii: 1H-NMR (400MHz, DMSO-Cf6) delta ppm 8.33 (s, 1 H), 7.95 (d, 1 H), 7.57 (d, 1 H), 7.30 (dd, 1 H), 4.16 (s, 3H). LCMS (method A): [MH]+ = 21 1/213, tR = 4.95 min. | |
29%; 42.5% | To a solution of 5-bromo-1 H-indazole (0.19 g, 0.94 mmol) in 3 ml_ of THF at 0 QC was added NaH (0.04 g, 1 .03 mmol). The reaction mixture was stirred at this temperature for 1 h before the addition of methyl iodide (0.09 ml_, 1 .41 mmol) at 0 QC. The reaction was allowed to warm to rt slowly and stirred for 2 h, quenched with water and concentrated in vacuo. The residue was diluted with water and extracted with DCM twice. The organic layers were combined, dried over Na2SO4 and concentrated. The crude products were purified by flash chromatography (hexane:EtOAc = 10:1 ) to give the title compound ii (88.7 mg, 42.5 %) and iii (60.9 mg, 29 %) as white solid, ii: 1H-NMR (400MHz, DMSO-d6) Dppm 8.02 (d, 1 H), 7.99 (d, 1 H), 7.64 (d, 1 H), 7.50 (dd, 1 H), 4.04 (s, 3H). LCMS (method A): [MH]+ = 21 1/213, tR = 5.19 min. iii: 1H-NMR (400MHz, DMSO-Cf6) deltappm 8.33 (s, 1 H), 7.95 (d, 1 H), 7.57 (d, 1 H),7.30 (dd, 1 H), 4.16 (s, 3H). LCMS (method A): [MH]+ = 21 1/213, tR = 4.95 min. |
Scheme 5:F G R Me HI R Et JK R Pr LM R iPr N Sodium hydride (60% in oil, 1.5 g, 37.5 mmol, 1.2 equiv) was added to a solution of 5- bromoindazole F (6 g, 30.6 mmol, 1 equiv) in DMF (60 mL) at RT. After stirring for 30 min, methyl iodide (2.83 mL, 45.9 mmol, 1.5 equiv) was added and the reaction stirred for another 2 h at RT. The reaction was quenched with sat. NaHC03, extracted with EtOAc (lx), dried over MgS04, filtered, and concentrated under reduced pressure to give a mixture of JV-l and N-2 methylated 5-bromoindazoles G and H, which were separated by silica-gel chromatography using 0?30 % EtOAc/hexanes as eluent. The Nl -alkylated regioisomer G elutes first, followed by the N2-methyl regioisomer H. Other N-l -alkylated 5-bromoindazoles (I, , M) were prepared by the same procedure, substituting the appropriate electrophile for methyl iodide (ethyl iodide, i-propyl iodide, n-propyi iodide). | ||
[000842] To a solution of 5-bromo-lH-indazole, 202A, (4.92 g, 25.0 mmol) in THF (300 mL) at 0 C was added NaH (1.10 g, 27.5 mmol). The reaction solution was stirred at this temperature for 1 hour before methyl iodide (5.32 g, 37.5 mmol) was added at 0 C. The reaction was allowed to warm to room temperature slowly, stirred for 2 hours, and quenched with water and concentrated in vacuo. The residue was diluted with water and extracted with dichloromethane (80 mL x 2). The organic layers were combined, dried over anhydrous sodium sulfate, and concentrated. The crude product was purified with flash column chromatography on silica gel (ethyl acetate in petroleum ether, 10% v/v) to give Compound 202B and Compound 202C. | ||
[000791j To a solution of Compound 125A (4.92 g, 25.0 mmol) in THF (300 mL) was added NaH (1.10 g, 27.5 mmol) at 0 C. The reaction solution was stirred at this temperature for 1 h before methyl iodide (5.32 g, 37.5 mmol) was added at 0 C. The reaction was allowed to warm to room temperature slowly, stirred for 2 h, and quenched with water and concentrated in vacuo. The residue was diluted with water and extracted with dichloromethane (80 mL x 2). The organic layers were combined, dried over anhydrous sodium sulfate, and concentrated. The crude product was purified with flash column chromatography on silica gel (ethyl acetate in petroleum ether, 10% v/v) to give Compound 125B and Compound 125C. For Compound 125B: LC-MS (ESI) mlz: 211 [M+H] ?H-NMR (CDC13, 400 MHz): (5(ppm) 4.06 (s, 3H), 7.26-7.28 (m, 1H), 7.44-7.48 (m, 1H), 7.86-7.87 (m, 1H), 7.91 (s, 1H). For Compound 125C: LC-MS (ESI) mlz: 211 [M+H] ?H-NMR (CDC13, 400 MHz) (5(ppm) 4.20 (s, 3H), 7.3 1-7.34 (m, 1H), 7.56-7.58 (m, 1H), 7.79-7.80 (m,1H), 7.84 (s, 1H). | ||
Sodium hydride (60% in oil, 1.5 g, 37.5 mmol) was added to a solution of 5-bromoindazole D (6 g, 30.6 mmol) in DMF (60 mL) at RT. After stirring for 30 min, methyl iodide (2.83 mL, 45.9 mmol) was added and the reaction stirred for another 2 h at RT. The reaction was quenched with sat. NaHCO3 (aq), extracted with EtOAc (1×), dried over MgSO4, filtered, and concentrated under reduced pressure to give a mixture of N-1 and N-2 methylated 5-bromoindazoles E and F, which were separated by silica-gel chromatography using 0?30% EtOAc/hexanes. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42%; 44% | Example 2004 Compound 2004A (1 g, 5.07 mmol) was dissolved in 20 mL of THF and reacted with sodium methoxide (10 mL, 5.07 mmol). After 30 min, iodomethane (1.3 mL, 20.3 mmol) was added. Reaction mixture was stirred for 5 hours at room temp, then it was added to ethyl acetate and water. The aqueous layer was extracted with ethyl acetate twice. All the organic layers were combined, washed with brine solution and dried over sodium sulfate. The solvent was removed by rotary evaporator and further purified by SiO2 column chromatography to give 2004B (470 mg, 44% yield) and 2004C (450 mg, 42% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69%; 77% | General procedure: NaH (6.1 mmol, 1.2 equiv) was slowly added to a solution of 5-bromoindole/indazole (5.1 mmol,1 equiv) in DMF (10 mL) at 0 C. The mixture was stirred at 0 C for 10 min then the alkylhalide (6.1 mmol, 1.2 equiv) was added at the same temperature. The reaction mixture wascontinued to stir at rt for 2 h. When the reaction was complete [TLC (EtOAc/hexane 1:5)], themixture was extracted with EtOAc (2 × 20 mL) and washed with water (2 × 20 mL). The organiclayer was separated, dried over anhydrous Na2SO4 and the solvent removed under reducedpressure. The residue obtained was purified by flash column chromatography [silica gel (230-400 mesh; Merck), EtOAc/hexane 1:5]. |
Tags: 465529-57-1 synthesis path| 465529-57-1 SDS| 465529-57-1 COA| 465529-57-1 purity| 465529-57-1 application| 465529-57-1 NMR| 465529-57-1 COA| 465529-57-1 structure
A221074 [1095539-84-6]
6-Bromo-1,3-dimethyl-1H-indazole
Similarity: 0.90
A221074 [1095539-84-6]
6-Bromo-1,3-dimethyl-1H-indazole
Similarity: 0.90
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