25999-04-6|Morpholine-4-sulfonamide| Ambeed

CAS No. :	25999-04-6
Formula :	C₄H₁₀N₂O₃S
M.W :	166.20
SMILES Code :	O=S(N1CCOCC1)(N)=O
MDL No. :	MFCD11171673
InChI Key :	WZWQJRQCWCFUTM-UHFFFAOYSA-N
Pubchem ID :	276739

Safety of [ 25999-04-6 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Computational Chemistry of [ 25999-04-6 ] Show Less

Physicochemical Properties

Num. heavy atoms	10
Num. arom. heavy atoms	0
Fraction Csp3	1.0
Num. rotatable bonds	1
Num. H-bond acceptors	5.0
Num. H-bond donors	1.0
Molar Refractivity	38.8
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	81.01 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	0.87
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	-1.53
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	-0.78
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	-1.36
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-1.3
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	-0.82

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	0.16
Solubility	240.0 mg/ml ; 1.44 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Highly soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	0.34
Solubility	360.0 mg/ml ; 2.16 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Highly soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	0.38
Solubility	394.0 mg/ml ; 2.37 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble

Pharmacokinetics

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) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	No
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-8.4 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	2.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	0.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	2.46

Application In Synthesis of [ 25999-04-6 ]

* 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.

Downstream synthetic route of [ 25999-04-6 ]

[ 25999-04-6 ] Synthesis Path-Downstream 1~55

1
[ 110-91-8 ]
[ 25999-04-6 ]

Yield	Reaction Conditions	Operation in experiment
17%	With SULFAMIDE; In 1,2-dimethoxyethane; at 100℃;	Step 1 : morpholine-4-sulfonamide; To a solution of morpholine (leq) in DME (0.3 M), 5 eq of sulfamide were added and the solution was heated at 100 0C overnight. The volatiles were removed in vacuo, the residue taken up in EtOAc and the organic phase washed with H2O and then brine. The organic phase was dried over Na2SO4, filtered and concentrated in vacuo to give the title compound (17 %); MS (ES+) m/z 167 (M+H)+
	With SULFAMIDE; In monoethylene glycol diethyl ether; at 120℃; for 11h;	5.00 g of sulfamide, 4.09 g of morpholine and 5 ml of 1,2-diethoxyethane were mixed and heated with stirring in an oil bath at 120C for 11 hours.. The reaction solution was air-cooled to room temperature and the crystal was washed with diethyl ether, washed with methanol and then dried under reduced pressure to obtain 5.98 g of the desired compound as an brownish crystal having a melting point of 158 to 161C.
	With SULFAMIDE; In 1,4-dioxane; for 48h;Heating / reflux;	Morpholine [(5ML)] and sulfamide [(1] [LG)] in 1,4-dioxane [(100ML)] were heated at reflux for 48h. The solvent was evaporated under reduced pressure and the resulting solid partitioned between EtOAc and water. The organic phase was collected and the aqueous phase was further extracted with EtOAc (x4). The combined organic extracts were dried [(MGS04)] and the solvent removed in vacuo. The solid residue was triturated with Et20 and filtered to give the subtitle compound as a white crystaline solid. Yield: 2. [1 G.] 'H [NMR A (DMSO)] 6.82 (2H, s), 3.66 (4H, [M),] 2.90 (4H, [M).]

References: [1]Phosphorus and Sulfur and the Related Elements,1985,vol. 25,p. 33 - 38.
[2]Patent: WO2006/46030,2006,A2 .Location in patent: Page/Page column 66.
[3]Patent: EP1400518,2004,A1 .Location in patent: Page 32.
[4]Patent: WO2004/11443,2004,A1 .Location in patent: Page 70.
[5]Patent: DE869065,1942, .

2
[ 5319-77-7 ]
[ 25999-04-6 ]
[ 594-42-3 ]
morpholine-4-sulfonic acid 6-methanesulfinyl-[1,3,4]thiadiazolo[2,3-<i>c</i>][1,2,4]thiadiazol-3-ylideneamide [ No CAS ]

References: [1]Journal of Pharmaceutical Sciences,1979,vol. 68,p. 182 - 185.

3
[ 75-77-4 ]
[ 25999-04-6 ]
[ 56839-97-5 ]

References: [1]Chemische Berichte,1975,vol. 108,p. 2340 - 2348.

4
[ 1189-71-5 ]
[ 25999-04-6 ]
[ 55680-19-8 ]

References: [1]Chemische Berichte,1975,vol. 108,p. 618 - 622.

5
[ 25999-04-6 ]
[ 2176-62-7 ]
[ 57840-78-5 ]

References: [1]Journal of Organic Chemistry USSR (English Translation),1975,vol. 11,p. 2077 - 2082.
Zhurnal Organicheskoi Khimii,1975,vol. 11,p. 2044 - 2049.

6
[ 25999-04-6 ]
[ 302-17-0 ]
[ 10539-93-2 ]

References: [1]Soviet progress in chemistry,1966,vol. 32,p. 368 - 370.
Ukrainskii Khimicheskii Zhurnal (Russian Edition),1966,vol. 32,p. 486 - 488.

7
[ 25999-04-6 ]
[ 1495-51-8 ]
[ 63698-81-7 ]

References: [1]Chemische Berichte,1977,vol. 110,p. 2368 - 2373.

8
[ 25999-04-6 ]
[ 52379-51-8 ]
[ 20804-20-0 ]

References: [1]Journal of Organic Chemistry USSR (English Translation),1968,vol. 4,p. 1572 - 1574.
Zhurnal Organicheskoi Khimii,1968,vol. 4,p. 1636 - 1639.

9
[ 25999-04-6 ]
[ 824-78-2 ]
(morpholine-4-sulfonyl)-phosphorimidic acid tris-(4-nitro-phenyl) ester [ No CAS ]

References: [1]Journal of Organic Chemistry USSR (English Translation),1970,vol. 6,p. 2247 - 2251.
Zhurnal Organicheskoi Khimii,1970,vol. 6,p. 2239 - 2243.

10
[ 25999-04-6 ]
[ 618-39-3 ]
[ 20804-20-0 ]

References: [1]Journal of Organic Chemistry USSR (English Translation),1968,vol. 4,p. 1572 - 1574.
Zhurnal Organicheskoi Khimii,1968,vol. 4,p. 1636 - 1639.

11
[ 25999-04-6 ]
[ 825-60-5 ]
[ 20804-20-0 ]

References: [1]Journal of Organic Chemistry USSR (English Translation),1968,vol. 4,p. 1572 - 1574.
Zhurnal Organicheskoi Khimii,1968,vol. 4,p. 1636 - 1639.

12
[ 25999-04-6 ]
[ 999-97-3 ]
[ 56839-97-5 ]

References: [1]Chemische Berichte,1975,vol. 108,p. 2340 - 2348.

13
[ 25999-04-6 ]
[ 30312-14-2 ]

References: [1]Journal of Organic Chemistry USSR (English Translation),1970,vol. 6,p. 2247 - 2251.
Zhurnal Organicheskoi Khimii,1970,vol. 6,p. 2239 - 2243.

14
[ 25999-04-6 ]
[ 28149-60-2 ]

References: [1]Journal of Organic Chemistry USSR (English Translation),1970,vol. 6,p. 496 - 498.
Zhurnal Organicheskoi Khimii,1970,vol. 6,p. 496 - 499.

15
[ 75-15-0 ]
[ 25999-04-6 ]
[ 77-78-1 ]
[ 134577-05-2 ]

References: [1]Synthesis,1991,p. 220 - 222.

Yield	Reaction Conditions	Operation in experiment
97%	With palladium on activated charcoal; hydrogen; In methanol; for 3h;	General procedure: To a solution of the compound of Reference Example 53-2 (540 mg, 1.423 mmol) in methanol (20 mL), palladium-carbon (760 mg) was added, and the mixture was stirred for 3 hours under hydrogen atmosphere. The reaction solution was filtered through Celite, and the filtrate was concentrated under reduced pressure to obtain the title compound (411 mg, 100%). 1H NMR (DMSO-d6, 300 MHz) delta 6.87 (m, 1H), 4.48-4.37 (m, 1H), 4.32-4.21 (m, 1H), 3.45-3.34 (m, 1H), 2.11-2.03 (m, 1H), 1.89-1.86 (m, 2H), 1.71-1.67 (m, 2H), 1.37-1.30 (m, 10H), 1.23-1.17 (m, 2H), 1.13-0.95 (m, 2H).
	In 1,4-dioxane; at 110℃; for 16h;	General procedure: N-Ethyl-N-methyl amine (2.95 g, 50 mmol) was added to a solution of Sulfamide (4 g, 41.6 mmol) in 1,4-Dioxane (40 mL) and continued stirring at 110C for 16 h. Reaction mass was concentrated under reduced pressure to afford the crude, which was purified by column purification (using neutral alumina and 10-70% ethyl acetate in Hexane as eluent) to afford N-Ethyl-N-methyl sulfamide (Int-30) as pale yellow oil. 1H NMR (300 MHz, DMSO-d6) delta ppm 6.7 (2H, s), 3.1-2.3 (2H, m), 2.6 (3H, s), 1.2-1.0 (3H, t).
	With SULFAMIDE; In 1,4-dioxane; at 110℃; for 16h;	General procedure: N-Ethyl-N-methyl amine (2.95 g, 50 mmol) was added to a solution of Sulfamide (4 g, 41.6 mmol) in 1,4-Dioxane (40 mL) and continued stirring at 110 C. for 16 h. Reaction mass was concentrated under reduced pressure to afford the crude, which was purified by column purification (using neutral alumina and 10-70% ethyl acetate in Hexane as eluent) to afford N-Ethyl-N-methyl sulfamide (Int-30) as pale yellow oil. 1H NMR (300 MHz, DMSO-d6) delta ppm 6.7 (2H, s), 3.1-2.3 (2H, m), 2.6 (3H, s), 1.2-1.0 (3H, t).

18
[ 33252-28-7 ]
[ 25999-04-6 ]
N-(5-cyanopyridin-2-yl)morpholine-4-sulfamide [ No CAS ]