Structure of 68774-77-6
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CAS No. : | 68774-77-6 |
Formula : | C5H3ClN4 |
M.W : | 154.56 |
SMILES Code : | ClC1=NC=C[N]2C1=NN=C2 |
MDL No. : | MFCD08272086 |
InChI Key : | VKZJRJVVFDDJKP-UHFFFAOYSA-N |
Pubchem ID : | 12582612 |
GHS Pictogram: | ![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 35.79 |
TPSA ? Topological Polar Surface Area: Calculated from | 43.08 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from | 1.16 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by | 1.07 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from | 0.78 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from | -0.29 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by | 0.74 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions | 0.69 |
Log S (ESOL):? ESOL: Topological method implemented from | -2.14 |
Solubility | 1.12 mg/ml ; 0.00727 mol/l |
Class? Solubility class: Log S scale | Soluble |
Log S (Ali)? Ali: Topological method implemented from | -1.57 |
Solubility | 4.2 mg/ml ; 0.0272 mol/l |
Class? Solubility class: Log S scale | Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by | -1.94 |
Solubility | 1.77 mg/ml ; 0.0115 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 | -6.48 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) | 2.14 |
* 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 |
---|---|---|
22% | Stage #1: With platinum(IV) oxide; palladium 10% on activated carbon; hydrogen In methanol for 34 h; Stage #2: With N-ethyl-N,N-diisopropylamine In methanol at 20℃; for 3 h; | After dissolution compound obtained in Step 2 (8.10 g) and platinum oxide (IV) and 10percent palladium / carbon (2g, 50percent water content) in methanol (8 mL), under an atmosphere of hydrogen 50psi (Parr) 34 time and stirred. After filtering the reaction solution at Hyflo Super Cel, the oil obtained by concentrating the solvent was dissolved in dichloromethane (200 mL), N, N-diisopropylethylamine (10 mL) and di-tert-butylcarbonate (11 .4g) was added was stirred for 3 hours at room temperature. The reaction solution was extracted three times with chloroform after adding a saturated aqueous sodium hydrogen carbonate solution, and the organic layer was concentrated after dried over sodium sulfate. The resulting residue to give the title compound purified by silica gel column chromatography (2.55g, 22percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | for 4h;Reflux; | It was stirred for 4 hours at reflux mixture of the compound obtained in Step 1 (8 g) and triethyl orthoformate (32 mL). The reaction solution was cooled to room temperature, the precipitated solid was washed after filtration, with ethanol, To give the title compound followed by drying under reduced pressure (8.10g, 95%). |
90.1% | at 80.0℃; | Intermediate b (5.0 g, 0.034 mol) was added to triethyl orthoformate (50 mL), and the reaction was carried out at 80 C. The reaction time was monitored with a plate. The reaction liquid was directly filtered with cold suction, and the filter cake was washed with petroleum ether. After the cake was dried, 4.8 g of a yellow powder was obtained with a yield of 90.1%. |
90.1% | at 80.0℃; | Intermediate b (5.0 g, 0.034 mol) was added to triethyl orthoformate (50 mL), and the reaction was carried out at 80 C. The reaction time was monitored with a plate. The reaction liquid was directly filtered with cold suction, and the filter cake was washed with petroleum ether. After the cake was dried, 4.8 g of a yellow powder was obtained with a yield of 90.1%. |
62% | In xylene; for 2h;Heating / reflux; | A mixture of l-(3-chloropyrazin-2-yl)hydrazine (0.90 g, 62 mmol), triethyl orthoformate (2.3 mL), 14 mmol), and dry xylene (15 mL) was refluxed with stirring for 2 h. The mixture was brought to RT, diethyl ether was added and the suspension was filtered. The solid collected was washed with diethyl ether to afford 8-chloro-[l,2,4]triazolo[4,3- ajpyrazine (0.60 g, 62% yield). MS m/z: 155.0 (M+l). |
62% | In xylene; for 2h;Reflux; | Step 3: 8-chloro-[1,2,4]triazolo[4,3-a]pyrazine A mixture of 1-(3-chloropyrazin-2-yl)hydrazine (0.90 g, 62 mmol), triethyl orthoformate (2.3 mL), 14 mmol), and dry xylene (15 mL) was refluxed with stirring for 2 h. The mixture was brought to RT, diethyl ether was added and the suspension was filtered. The solid collected was washed with diethyl ether to afford 8-chloro-[1,2,4]triazolo[4,3-a]pyrazine (0.60 g, 62% yield). MS m/z: 155.0 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate; In ethanol; N,N-dimethyl-formamide; at 45.0℃; for 96h; | A mixture of (0.070 g, 0.13 mmol), 8-chloro-[l,2,4]triazolo[4,3-a]pyrazine (0.020 g, 0.13 mmol) and sodium carbonate monohydrate (0.016 g, 0.13 mmol) in ethanol (2 mL) and dimethylformamide (2 mL) was heated at 45 C for 4 days. The mixture was brought to RT, concentrated, and the residue was dissolved in ethyl acetate. The organic phase was washed with water, brine, dried over <n="88"/>MgSO4, filtered, concentrated, and purified by HPLC to afford (2R,3,S)-3- ([l,2,4]triazolo[4,3-a]pyrazin-8-ylamino)-4-(3,5-difluorophenyl)-l-((R)-2,2- spirocyclobutane-6-neopentyl-3,4-dihydro-2H-pyrano[2,3-b]pyridine-4-ylamino)butan-2- ol as a light yellow solid. MS m/z: 577.8 (M+l). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate; In ethanol; N,N-dimethyl-formamide; at 60.0℃; for 17h; | To a solution of 8-chloro-[l,2,4]triazolo[4,3-a]pyrazine (0.032 g, 0.21 mmol) and sodium carbonate monohydrate (0.026 g, 0.21 mmol) in ethanol (2 mL) and dimethylformamidewas added the chroman-amine (0. 89 g, 0.21 mmol). The resulting mixture was stirred and heated at 60 0C for 17 h. The mixture was concentrated and the residue was dissolved in ethyl acetate, washed with water, brine, dried over Na2SO4, filtered, concentrated, and purified by HPLC to afford a light yellow solid as 2R,3S)-3-([l,2,4]triazolo[4,3-a]pyrazin-8-ylamino)-l-((R)-6-bromo-2,2- spirocyclobutanechroman-4-ylamino)-4-phenylbutan-2-ol. MS m/z: 551.1 (M+l). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In isopropyl alcohol; | The following examples in Table I were prepared by Methods A (Scheme 7), B (Scheme 8) or C (Scheme 9) and/or steps analogous to those described in Examples 6, 9, 11 and 21-23 above.Scheme 7 illustrates how one may construct the R1 to amine-backbone bond, where R1, as shown, is an aromatic moiety. Intermediate 8' can be heated in a microwave oven with a desirably substituted chloro-substituted aromatic compound 18 in the presence of a suitable base, such as dnsopropylethylamine (DIEA) in a suitable solvent, such as isopropyl alcohol (IPA) to afford the desired product compound 19 of Formula I or II. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate monohydrate; In ethanol; N,N-dimethyl-formamide; at 45.0℃; for 96h; | A mixutire of (0.070 g, 0.13 mmol), <strong>[68774-77-6]<strong>[68774-77-6]8-chloro-[1,2,4]triazolo[4,3-a]pyrazin</strong>e</strong> (0.020 g, 0.13 mmol) and sodium carbonate monohydrate (0.016 g, 0.13 mmol) in ethanol (2 mL) and dimethylformamide (2 mL) was heated at 45 C. for 4 days. The mixture was brought to RT, concentrated, and the residue was dissolved in ethyl acetate. The organic phase was washed with water, brine, dried over MgSO4, filtered, concentrated, and purified by HPLC to afford (2R,3,S)-3-([1,2,4]triazolo[4,3-a]pyrazin-8-ylamino)-4-(3,5-difluorophenyl)-1-((R)-2,2-spirocyclobutane-6-neopentyl-3,4-dihydro-2H-pyrano[2,3-b]pyridine-4-ylamino)butan-2-ol as a light yellow solid. MS m/z: 577.8 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate monohydrate; In ethanol; N,N-dimethyl-formamide; at 60.0℃; for 17h; | Example 22 (2R,3S)-3-([1,2,4]triazolo[4,3-a]pyrazin-8-ylamino)-1-((R)-6-bromo-2,2-spirocyclobutanechroman-4-ylamino)-4-phenylbutan-2-ol. To a solution of <strong>[68774-77-6]<strong>[68774-77-6]8-chloro-[1,2,4]triazolo[4,3-a]pyrazin</strong>e</strong> (0.032 g, 0.21 mmol) and sodium carbonate monohydrate (0.026 g, 0.21 mmol) in ethanol (2 mL) and dimethylformamide was added the chroman-amine (0.89 g, 0.21 mmol). The resulting mixture was stirred and heated at 60 C. for 17 h. The mixture was concentrated and the residue was dissolved in ethyl acetate, washed with water, brine, dried over Na2SO4, filtered, concentrated, and purified by HPLC to afford a light yellow solid as 2R,3S)-3-([1,2,4]triazolo[4,3-a]pyrazin-8-ylamino)-1-((R)-6-bromo-2,2-spirocyclobutanechroman-4-ylamino)-4-phenylbutan-2-ol. MS m/z: 551.1 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With N,N-diethyl-N-isopropylamine; at 120.0℃; for 2h; | A mixture of 8-chloro-[l,2,4]triazolo[4,3-a]pyrazine (620 mg, 4.0 mmol) and (S)-tert-butyl pyrrolidin-3-ylcarbamate (1.2 g, 6.5 mmol) in diethylisopropyl amine (3 mL) was heated to 120 C. for 2 h. After cooling to room temperature, the mixture was diluted with 10% MeOH in EtOAc and washed with saturated aqueous solutions of KH2PO4 and NaHCO3, followed by brine. The organic layerwas concentrated in vacuo and the residue purified by flashchromatography (SiO2, 2 to 5% MeOH in CH2Cl2 as eluent) to give the desired compound as a foam (1.15 g, 95% yield, which was used directly for the next step). MS: (ES) m/z305.2 (M+H+). |
Tags: 68774-77-6 synthesis path| 68774-77-6 SDS| 68774-77-6 COA| 68774-77-6 purity| 68774-77-6 application| 68774-77-6 NMR| 68774-77-6 COA| 68774-77-6 structure
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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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