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Limited Quantity | USD 15-60 |
Inaccessible (Haz class 6.1), Domestic | USD 80+ |
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CAS No. : | 99584-48-2 | MDL No. : | MFCD22548154 |
Formula : | C3HCl2N3 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | DHFJTUKAWMNXNY-UHFFFAOYSA-N |
M.W : | 149.97 | Pubchem ID : | 17909064 |
Synonyms : |
|
Num. heavy atoms : | 8 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.0 |
Num. rotatable bonds : | 0 |
Num. H-bond acceptors : | 3.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 29.85 |
TPSA : | 38.67 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.42 cm/s |
Log Po/w (iLOGP) : | 1.62 |
Log Po/w (XLOGP3) : | 1.12 |
Log Po/w (WLOGP) : | 1.18 |
Log Po/w (MLOGP) : | 0.36 |
Log Po/w (SILICOS-IT) : | 2.1 |
Consensus Log Po/w : | 1.28 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 2.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -2.03 |
Solubility : | 1.4 mg/ml ; 0.00932 mol/l |
Class : | Soluble |
Log S (Ali) : | -1.53 |
Solubility : | 4.47 mg/ml ; 0.0298 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -2.49 |
Solubility : | 0.482 mg/ml ; 0.00321 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 2.17 |
Signal Word: | Danger | Class: | 8 |
Precautionary Statements: | P264-P270-P280-P301+P312+P330-P305+P351+P338+P310-P501 | UN#: | 1759 |
Hazard Statements: | H302-H318 | Packing Group: | Ⅲ |
GHS Pictogram: |
* 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 |
---|---|---|
With hydrogenchloride In water at 80℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate In 1,4-dioxane; water |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76.6% | With N-ethyl-N,N-diisopropylamine In 1,4-dioxane at 50℃; for 3h; | 1.A; 2.A; 29.A Step A: (3ri,,4ri,)-3-Methyl-2-oxa-8-azaspiro[4.5]decan-4-amine dihy drochloride (320 mg, 1.3 mmol) was diluted with dioxane (6 mL), f ollowed by the addition of DIEA (815 pL, 4.67 mmol) and 3,6-dichloro-l,2,4-triazine (200 mg, 1.33 mmol). The reaction was heated to 50 °C and stirred for 3 hours. The reaction was allowed to cool and diluted with DCM/IPA and 10% sodium carbonate. The layers were separated, and the aqueous was extracted twice with DCM/IPA. The organics were combined, dried over MgS0 , filtered and concentrated. The material was purified on silica gel eluting with 1-10% methanol/DCM (1% NH4OH) to afford (3k,4k)-8-(6-chloro- l , 2, 4-triazin-3-yl )-3 -methyl -2-oxa-8- azaspiro[4.5 Jdecan -4-amine (290 mg, 1.02 mmol, 76.6% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69.1% | With N-ethyl-N,N-diisopropylamine In 1,4-dioxane at 50℃; for 3h; | 3.A Step A: /erZ-Butyl ((li?,3s,5A)-8-azabicyclo[3.2.1]octan-3-yl)carbamate (226 mg, 1.00 mmol) was diluted with dioxane (5 mL), followed by the addition of DIEA (611 pL, 3.50 mmol) and 3,6-dichloro-l,2,4-triazine (150 mg, 1.00 mmol). The reaction was heated to 50 °C and stirred for 3 hours. The reaction was allowed to cool, diluted with DCM/IPA and 10% sodium carbonate. The layers were separated, and the aqueous was extracted twice with DCM/IPA. The organics were combined, dried over MgS0 , filtered and concentrated. The material was purified on silica gel eluting with 10-50% ethyl acetate/hexanes to afford tert- butyl ((li?,3s,5A)-8-(6-chloro-l,2,4-triazin-3-yl)-8-azabicyclo[3.2.1]octan-3-yl)carbamate (235 mg, 0.692 mmol, 69.1% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
11% | With N-ethyl-N,N-diisopropylamine In 1,4-dioxane at 50℃; for 3h; | 6.A Step A: (i?)-/V-((A)-l ,3-Dihydrospiro[indene-2,4'-piperidin]-l-yl)-2- methylpropane-2-sulfmamide(l 63 mg, 0.53 mmol) was diluted with dioxane (2 mL), followed by the addition of DIEA (326 pL, 1.9 mmol). After stirring for 5 minutes, 3,6-dichloro-l,2,4- triazine (80 mg, 0.53 mmol) was added. The reaction was heated to 50 °C and stirred for 3 hours. The reaction was allowed to cool and diluted with DCM/IPA and 10% sodium carb onate. The layers were separated, and the aqueous was extracted twice with DCM/IPA. The organics were combined, dried over MgS0 , filtered and concentrated. The material was purified on silica gel eluting with 1-10% methanol/DCM (l% NH OH) to afford (R)-N-((S)- '-(6-chloro- l ,2,4-triazin-3-yl)-l ,3-dihydrospiro[indene-2,4'-piperidin]-l -yl)-2-methylpropane-2- sulfinamide (25 mg, 0.060 mmol, 1 1 % yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | Stage #1: tert-butyl (R)-5-(((R)-tert-butylsulfinyl)amino)-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4’-piperidine]-1‘-carboxylate With trifluoroacetic acid In dichloromethane for 1h; Stage #2: 3,6-dichloro-1,2,4-triazine With triethylamine In 1,4-dioxane at 50℃; for 3h; Stage #3: 2-amino-3-chloropyridine-4-thiol sodium salt In 1,4-dioxane at 90℃; for 18h; | 16.A; 16.B Step A: fert-Butyl (f?)-5-(((f?)-fer/-butylsulfinyl)amino)-5,7- dihydrospiro[cyclopenta[A]pyridine-6,4'-piperidine]-l'-carboxylate (0.193 g, 0.474 mmol) was dissolved in DCM (3 mL), and then 2,2,2-trifluoroacetic acid (0.270 g, 2.37 mmol) was added. After stirring for 1 hour, reaction was evaporated, and the remaining TFA salt was used in the next step without further purification. Step B: (f?)-/V-((f?)-5,7-Dihydrospiro[cyclopenta[6]pyridine-6,4'-piperidin]-5- yl)-2-methylpropane-2-sulfmamide (0.07 g, 0.23 mmol) as TFA salt was dissolved in dioxane (4 mL), and TEA (0.16 mL, 1.1 mmol) was added to the solution. 3,6-Dichloro-l,2,4-triazine (0.032 g, 0.22 mmol) was added, and the mixture was heated up to 50 °C for 3 hours. Sodium 2-amino-3-chloropyridine-4-thiolate (0.050 g, 0.27 mmol) was added to the reaction mixture, and the mixture was heated up to 90 °C for 18 hours. The reaction was cooled down to room temperature, quenched with water (10 mL) and extracted with EtOAc (3 X 15 mL). The combined organic layers were washed with brine, dried and evaporated to give a residue. The residue was purified using 24 g silica gel column (MeOH/DCM mixture 2-20%) provided (R A-((i?)-r-(6-((2-amino-3-chloropyridin-4-yl)thio)-l,2,4-triazin-3-yl)-5,7- dihydrospiro[cyclopenta[6]pyridine-6,4'-piperidin]-5-yl)-2-methylpropane-2-sulfinamide (0.081 g, 0.15 mmol, 65% yield) as a solid m/z (esi/APCI) M+1 =545.2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
47% | With triethylamine In 1,4-dioxane at 100℃; | 24.B Step B: (/i)-A/-(C.y)-5,7-Dihydrospiro[cyclopenta[/>]pyridine-6,4'-piperidin]-5- yl)-2-methylpropane-2-sulfmamide (0.15 g, 0.49 mmol) and 3,6-dichloro-l,2,4-triazine (0.084 g, 0.56 mmol) were dissolved in 1 ,4-dioxane (1.5 mL, 0.375 mmol). Triethylamine (0.21 mL, 1.47 mmol) was added, and the resulting solution was stirred at 100 °C overnight. The crude material was loaded onto a 40g silica gel column and isolated over a gradient of 50- 100%EtO Ac/hexane to afford (R)-N-((S)- '-(6-chloro- l ,2,4-triazin-3-yl)-5,7- dihydrospiro[cyclopenta[Z>]pyridine-6,4'-piperidin]-5-yl)-2-methylpropane-2-sulfinamide (0.099 g, 0.23 mmol, 47% yield) as a solid m/z (esi/APCI) M+1 = 421.2. |