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Type | HazMat fee for 500 gram (Estimated) |
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Structure of 202658-88-6
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 202658-88-6 |
Formula : | C3H6ClNO3S |
M.W : | 171.60 |
SMILES Code : | O=C(NS(=O)(C)=O)CCl |
MDL No. : | MFCD20637131 |
InChI Key : | BKLFBPWLPOUGTM-UHFFFAOYSA-N |
Pubchem ID : | 23596666 |
GHS Pictogram: |
![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H302-H314-H319 |
Precautionary Statements: | P280-P301+P312-P303+P361+P353-P304+P340-P305+P351+P338-P310 |
Class: | 8 |
UN#: | 3261 |
Packing Group: | Ⅲ |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.67 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 33.3 |
TPSA ? Topological Polar Surface Area: Calculated from |
71.62 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.1 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-0.27 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.38 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-1.04 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.26 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-0.22 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.54 |
Solubility | 50.0 mg/ml ; 0.291 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.78 |
Solubility | 28.8 mg/ml ; 0.168 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.21 |
Solubility | 10.6 mg/ml ; 0.0618 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 |
No |
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) |
No |
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 |
-7.54 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 |
2.0 |
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 |
1.0 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) |
2.08 |
* 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 |
---|---|---|
94% | In ethyl acetate; at 65℃; for 12h;Large scale; | In a 2-liter reaction flask, 1 liter of ethyl acetate and 66 grams of methylsulfonamide were added, and 109 grams of chloroacetyl chloride was gradually added; the temperature was gradually increased to 65C for 12 hours until the end of the reaction.The reaction solution gradually cooled to 0 degree, and a large amount of white solid precipitated; it was filtered and dried to obtain 112 g of solid SLP-10b (X=Cl).Yield: 94%.H NMR (400MHz, CDCl3): delta 4.02 (s, 2H), 3.28s, 3H)ESI/MS+(m/z):171 |
74% | In acetic acid butyl ester; for 8h;Heating / reflux; | 26.8 mol of chloroacetyl chloride and 25.5 mol of methanesulfonamide in 10.2 L of butyl acetate are slowly boiled at reflux. After 8 h, the mixture is cooled to 20 C. The precipitated solid is filtered off and stirred in 4 L of butyl acetate. The precipitated solid is dried at 50 C. in a fan-assigned drying cabinet. Yield 74% |
14 g | In acetic acid butyl ester; at 125℃; for 16h; | Methane sulfonamide (10 gm) and n-butylacetate (80 mL) were charged into a 250 mL round bottom flask at 30C. Chloroacetylchloride (21 .37 gm) was added slowly over a period of 10 minutes at 30C. Temperature of the reaction mass was raised to 125C and maintained reflux for 16 hours. Progress of the reaction was monitored by TLC and after completion of the reaction the mass was cooled to 20C and stirred for 1 hour at 20C. Reaction mass was filtered and the wet solid was washed with n- butylacetate (10 mL). The wet solid was taken into another 100 mL round bottom flask and n-butylacetate (50 mL) was added and stirred for 30 minutes at 20C. The precipitation was filtered and the solid was suck dried. The material was dried at 45 under vacuum for 5 hours to yield 14 gm of title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | In sulfolane; at 130℃; for 5.83333h; | 2.5 mol of G and 2.5 mol of H in 1.3 L of sulfolane are heated at 130 C. After 5 h and 50 min, the mixture is cooled to 50 C. 2.5 L of acetone are added and the mixture is further cooled to room temperature. The precipitated solid is filtered off and washed with acetone. The precipitated solid is stirred in 1.6 L of warm demineralized water. 1.6 L of ethanol are added and the mixture is cooled. The precipitated solid is filtered off and washed with ethanol. Yield: 53% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89.7% | With potassium tert-butylate; In tetrahydrofuran; at 0 - 5℃; for 1h; | To the reaction flask was added 4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]-1-butanol (100 g, 1 eq), THF (1 L), Stir and dissolve;Cooling to 0-5 C; potassium tert-butoxide (155.21 g, 5 eq) was added in portions, temperature control 0-5 C;N-(Chloroacetyl)methylsulfonamide (142 g, 3 eq) was dissolved in tetrahydrofuran (500 mL).Dropped into the above reaction bottle, the temperature is controlled at 0-5 C,The addition is completed in about 1 hour; after the reaction is completed, the reaction is stopped;The reaction solution was concentrated to dryness and dichloromethane (1L) was added.Water (1L); adjust the pH to 5-6 with 1M hydrochloric acid, dispense,The aqueous phase was extracted with dichloromethane (500 mL).The organic phase was washed with water (1 L). The organic phase was concentrated to dryness, anhydrous ethanol (1 L) was added, and the crystals were stirred to give 93.69 g.89.7%, purity 98.5%. |
890 mg | Potassium tertiary butoxide (700 mg) and dimethylsulfoxide (50 mL) were charged into a 100 mL round bottom flask at 30C. 4-[N-(5,6-diphenylpyrazin-2-yl)-N- isopropylamino]-1 -butanol (1 gm) at 28 C and the resulted mixture was stirred for 15 minutes. <strong>[202658-88-6]2-chloro-N-(methylsulfonyl)acetamide</strong> (1 .2 gm) was added at the resulted was added at the resulted mixture was stirred at 30C for 16 hours. Progress of the reaction was monitored by TLC and after completion of the reaction the reaction mass was poured into cold water and pH was adjusted to 6.5 with 1 N hydrochloric acid (-15 mL). The aqueous layer was extracted with ethylacetate, dried over anhydrous magnesium sulphate and then concentrated. The residue was purified by silica gel column chromatography using 2% Methanol in DCM as eluent to obtain 890 mg of Selexipag. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With potassium tert-butylate; In 1-methyl-pyrrolidin-2-one; at 20℃; for 12h;Large scale; | In a 10-liter reaction kettle, 192 g of SLP-9 was dissolved in 2 liters of N-methylpyrrolidone; 67 g of potassium tert-butoxide was slowly added, and then 112 g of SLP-10b (0.7 mol) was added in portions; stirring at room temperature 12 Hours to the end of the reaction.Slowly cool to 0 C., add 2 kg of ice water and add 3 liters of ethyl acetate, stir and stand for phase separation; the organic phase is dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product; the crude product is ethyl acetate/ The petroleum ether crystallized and concentrated to give 219 g of a pale yellow solid SLP-11 (Siripag).Yield: 83%, purity 99.2%. |
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