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Structure of 147751-16-4

Chemical Structure| 147751-16-4

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Product Details of [ 147751-16-4 ]

CAS No. :147751-16-4
Formula : C6H13NO4S
M.W : 195.24
SMILES Code : CC(C)(C)OC(=O)NS(C)(=O)=O
MDL No. :MFCD13194912
Boiling Point : No data available
InChI Key :GAIZFMKSOHADOV-UHFFFAOYSA-N
Pubchem ID :10081367

Safety of [ 147751-16-4 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 147751-16-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 0
Fraction Csp3 0.83
Num. rotatable bonds 4
Num. H-bond acceptors 4.0
Num. H-bond donors 1.0
Molar Refractivity 44.43
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

80.85 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

1.34
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

0.5
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

1.55
Log Po/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.

-0.27
Log Po/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

-0.76
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.47

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-1.1
Solubility 15.5 mg/ml ; 0.0792 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-1.77
Solubility 3.33 mg/ml ; 0.0171 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very 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

-1.15
Solubility 13.9 mg/ml ; 0.0711 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.

-7.14 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

1.0
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)

2.37

Application In Synthesis of [ 147751-16-4 ]

* 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 [ 147751-16-4 ]

[ 147751-16-4 ] Synthesis Path-Downstream   1~36

  • 1
  • [ 75-21-8 ]
  • [ 147751-16-4 ]
  • tert-butyl N-[(3-hydroxypropyl)sulfonyl]carbamate [ No CAS ]
  • 2
  • [ 96-09-3 ]
  • [ 147751-16-4 ]
  • tert-butyl N-[(3-hydroxy-3-phenylpropyl)sulfonyl]carbamate [ No CAS ]
  • 3
  • [ 147751-16-4 ]
  • [ 75-56-9 ]
  • tert-butyl N-[(3-hydroxybutane)sulfonyl]carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
25% n-BuLi (10.2 mL, 1 M in hexane, 10.2 mmol) was added to a solution of diisopropylamine (1.7 mL, 10.2 mmol) in THF (20 mL) at -78 C, and the resulting mixture was stirred for 10 minutes at -78 C and then 30 minutes at -5 C. The reaction mixture was again cooled to -78 C, then a solution of B1 (1.0 g, 5.1 mmol) in THF (10 mL) was added dropwise to this reaction mixture (maintaining the reaction mixture temperature at -78 C) and the stirring was continued for 20 minutes. A solution of propylene oxide (0.47 mL, 6.7 mmol) in THF (15 mL) was added dropwise to this reaction mixture at -78 C and stirring was continued for 30 minutes. The reaction mixture was slowly warmed to room temperature and stirring was continued for 16 h. The mixture was poured onto an ice-cold saturated aqueous NH4CI solution. The resulting precipitate was dissolved by addition of water, and the mixture was acidified with 1 N HCI to pH = 3. The aqueous layer was extracted with DCM. The organic layer was washed with brine, dried over anhydrous Na2S04, concentrated to get residue which was chromatographed on silica gel (230 - 400 mesh) using diethyl ether as eluent to obtain B2 as a colorless oil (0.3 g. 25%). Rf: 0.3 (Et20). LCMS m/z = 252.1 (M - 1 )
25% To a 100 mL 3-necked rmmd bottom flask purged with and maintained under an inertatmosphere of nitrogen was added a solution of diisopropy lamine (1.03 g, 10.18 mmoL 2.00equiv.) in tetrahydrofuran (20 mL), the solution was cooled to -78C. A 2.5M solution ofn-1 0 BuLi in THF (4.1 mL, 2.00 equiv .) was added dropwise with stirring during a 10 min period.The rnixture was stirred for another 10 min at this temperature. A solution ofteli-butyl Nmethanesulfonylcarbamate216b (1 g, 5.12 mmol, 1.00 equiv.) in tetrahydrofuran (10 mL)-vvas added drop wise with stirring at -78C during a l 0 min period. Tile reaction wascontinued for 20 min. Then, a solution of2-methyloxirane (298 mg, 5.13 mmol, 1.00 equiv.)15 in tetrahydrofuran (10 mL) 1v·as added dropwise with stirring at -78C in a 15 rnin period.The reaction wa.s continued f()r 30min at this low temperature. Cooling bath was removed,and the reaction mixture was stirred at room temperature overnight. The mixture was cooledin an ice/salt bath, quenched by the addition of 40 mL of a saturated NH4Cl aqueous solution.The pH value of the solution vas adjusted to 3 using a 2M hydrogen chloride aqueous20 solution. Tile aqueous rnixture wa<; extracted with ethyl acetate (1 00 mL x 2), and thecombined organic extracts w·ere washed w·ith brine (100 mL x 3), dried over anhydroussodium sulfate and concentrated under vacuum. The residue was purified by silica gel colunmchromatography eluting with ethyl acetate/petroleum ether (1:2) to furnish tert-hutyl N-[(3-hydroxybutane)sulfonyl]carbamate 216c (320 mg, 25%) as a light yellow oil
17 g To a solution of diisopropylamine (15.54 g, 163.66 mmol) in THF (150 mL) was added n- BuLi (61.5 mL, 153.75 mmol, 2.5 M in hexane) at -78 C. The mixture was stirred at -78 C for 20 mins. Then a solution of tert-butyl methylsulfonylcarbamate (compound I-13a, 15.0 g, 76.8 mmol) in THF (150 mL) was added to the above mixture drop- wise over a period of 20 mins. The mixture was stirred at -50 C for 30 mins, followed by addition of a solution of propylene oxide (5.58 g, 96.03 mmol, 6.72 mL) in THF (90 mL) over 30 mins at -78 C. The mixture was allowed to warm up to rt and stirred for 15 hrs. The mixture was poured into aqueous NH4C1 solution (210 mL). The resulting precipitate was collected and dissolved with water, followed by acidification with 2 M HC1 to pH=3. The resulting aqueous mixture was extracted with DCM (100 mL) for 5 times. The combined organic layer was washed with brine, dried over anhydrous Na2S04 and concentrated under reduced pressure. The residue was purified by column chromatography to give compound I-13b (17 g) as a colorless oil. MS obsd. (ESI+) [(M+H)+] : 254
  • 4
  • [ 27701-23-1 ]
  • [ 147751-16-4 ]
  • [ 914801-93-7 ]
YieldReaction ConditionsOperation in experiment
71% n-BuLi (2.5 M in hexane, 19 mL, 47.7 mmol, 3.1 equiv) was added dropwise to freshly distilled (i-Pr)2NEt (8.30 mL, 50.7 mmol, 3.30 equiv) in THF (50 mL) at 0 C. The mixture was stirred for 30 minutes, then N-Boc-methylsulfonamide (3.00 g, 15.3 mmol, 1 equiv) in THF (50 mL) was added and the reaction stirred for a further 1 hour at 0 C. Next, methyl 2-methoxymethoxybenzoate (3.00 g, 16.9 mmol, 1.1 equiv) in THF (10 mL) was added and the reaction was stirred for 3 hours at 0 C. The reaction mixture was quenched with saturated aq NaCl (50 mL) and 0.5 M aq NaH2PO4 (50 mL) and extracted with EtOAc (3×50 mL) and the combined organic extracts were dried (Na2SO4), and concentrated under reduced pressure. Purification by flash chromatography (30:70 EtOAc/hexane) afforded the title compound (3.93 g, 71%) as a white solid: mp 128-129 C.; Rf 0.7 (70:30 EtOAc/hexane); 1H NMR (600 MHz, CDCl3) delta 1.48 (s, 9H), 3.52 (s, 3H), 5.11 (s, 2H), 5.31 (s, 2H), 7.07 (t, J=7.2 Hz, 1H), 7.23 (d, J=8.4 Hz, 1H), 7.38 (br s, 1H), 7.50 (t, J=7.8 Hz, 1H), 7.78 (d, J=7.8 Hz, 1H); 13C NMR (150 MHz, CDCl3) delta 28.0, 56.8, 61.6, 84.4, 94.8, 115.0, 122.0, 126.3, 130.9, 135.4, 149.6, 156.9, 188.9; HRMS (ESI+) calcd for C15H21NNaO7S [M+Na]+ 382.0931, found 382.0908 (error 6.0 ppm).
  • 5
  • [ 1002761-79-6 ]
  • [ 147751-16-4 ]
  • [ 1002761-80-9 ]
YieldReaction ConditionsOperation in experiment
80% With potassium carbonate; In N,N-dimethyl acetamide; at 55℃; for 16h;Product distribution / selectivity; Part F. Preparation of N-tert-butyl ester-N-(4-benzylsulfanyl-5-nitro-thiophen-3-ylmethyI> methanesulfonamide.; Method A:; The product from Part E (32.46 g, 108.27 mmol) was dissolved in dimethyl acetamide (162 mL) and to the solution was added N-tert-butyl ester- methanesulfonamide (22.3 g, 114.22 mmol) and potassium carbonate (10.51 g, 76.04 mmol). The resulting solution was heated to 55 0C for 16 h. To the cooled reaction mixture was added ethyl acetate (444 mL) and the solution was washed with a 7% aqueous sodium chloride (3 x 444 mL) solution. The solvent was removed under vacuum and the residue was dissolved in ethanol. The product crystallized and was isolated by filtration and washed with cold ethanol to provide 39 g (80%) of N-tert-butyl ester-N-(4-benzylsulfanyl-5-nitro-thiophen-3-ylmethyl)- methanesulfonamide as a light yellow solid. 1H-NMR(DMSOd6) delta 1.42 (9H, s), 3.41 (3H, s), 4.19 (2H, s), 4.63 (2H, s), 7.1-7.3 (5H, m), 7.62 (IH, s); 13C-NMR (DMSOd6) delta 27.50J9.24, 41.76, 44.99, 84.09, 126.92, 127.40, 127.93, 128.26, 131.33, 136.21, 141.48, 150.16, 150.81; DCI-MS 476 (M+ 18).
  • 6
  • [ 686271-29-4 ]
  • [ 147751-16-4 ]
  • [ 1002761-80-9 ]
YieldReaction ConditionsOperation in experiment
57% With diethylazodicarboxylate; trimethylphosphane; In tetrahydrofuran; toluene; at 25℃; for 3.5h; Boc-N-methanesulfonamide (11.0 g, 56.3 mmol), trimethylphosphine (56.1 mL of a 1.0 M solution in tetrahydrofuran, 56.1 mmol), and a 40 wt. % solution of diethyl azodicarboxylate in toluene (25.6 mL, 56.0 mmol) were added sequentially to a solution of (4-benzylsulfanyl-5-nitro-thiophen-3-yl)-methanol (10.52 g, 37.4 mmol) in tetrahydrofuran (300 mL) at 25 C. The mixture was stirred for 3.5 h at 25 C., and then was concentrated in vacuo. Purification of the residue by flash column chromatography (Merck silica gel 60, 40-63 mum; 20% ethyl acetate in hexanes) afforded the desired product, Boc-N-(4-benzylsulfanyl-5-nitro-thiophen-3-ylmethyl)-methanesulfonamide (9.79 g, 21.3 mmol, 57%), as a dark brown oil. 1H NMR (400 MHz, CDCl3) delta: 1.50 (9H, s), 3.29 (3H, s), 4.19 (2H, s), 4.68 (2H, s), 7.15-7.18 (2H, m), 7.22-7.25 (3H, m), 7.40 (1H, s).
Method B:; To a solution of N-Boc methanesulfonamide (12.00 g, 61.5 mmole) and IM of trimethylphosphine (61.5 mL, 61.5 mmole) in THF was added (4-benzylsulfanyl-5-nitro-thiophen-3-yl)- methanol (11.5 g, 40.9 mmole) in 135 mL THF over 15 min at ~ 25 0C. The resulting solution was stirred at - 25 0C for ~ 10 min., and 26.7 g of 40% DEAD solution in toluene (26.7 g, 61.4 mmole) added slowly over ~ 10 min (slightly exothermic, water bath cooling). The reaction mixture was stirred at ~ 25 0C overnight or until the starting material was consumed as indicated by HPLC. The reaction mixture was concentrated to dryness, and ethyl acetate (200 mL) and 5% nuaHCtheta3 aq. Solution (200 mL) added. The upper organic was washed with 5% NaHCO3 (200 mLx2), and 25% brine (200 mL). The organic was dried over MgSO4, filtered. The filtrate was concentrated to ~ 50-60 mL volume (some solid), diluted with heptane (50 mL). The solid was filtered off, rinsed with ethyl acetate: heptane (1:1, 20 mL). The filtrate was concentrated to ~ 40 mL volume, chromatographed om a silica gel column (250 g), eluting with heptane :acetone (4:1). The main fractions of product were pooled, and concentrated to dryness to yield an oil (18.0 g), which was crystallized from abs ethanol to give 14.1 g product of N-tert-butyl ester- N-(4-benzylsulfanyl-5-nitro-thiophen-3-ylmethyl)-methanesulfonamide as a light yellow solid.
  • 13
  • [ 198226-65-2 ]
  • [ 147751-16-4 ]
  • [ 942066-39-9 ]
  • 14
  • [ 147751-16-4 ]
  • C16H23NO6S [ No CAS ]
  • 15
  • [ 147751-16-4 ]
  • C10H18NO4SC4H9O [ No CAS ]
  • 19
  • [ 147751-16-4 ]
  • [ 914801-94-8 ]
  • 20
  • [ 147751-16-4 ]
  • [ 914801-95-9 ]
  • 21
  • [ 147751-16-4 ]
  • [ 881652-42-2 ]
  • 23
  • [ 147751-16-4 ]
  • tert-butyl N-[(3-oxo-3-phenylpropyl)sulfonyl]carbamate [ No CAS ]
  • 24
  • [ 147751-16-4 ]
  • [ 206198-17-6 ]
  • 25
  • [ 147751-16-4 ]
  • C32H42N2O9S [ No CAS ]
  • 26
  • [ 147751-16-4 ]
  • C11H15NO5S [ No CAS ]
  • 27
  • [ 147751-16-4 ]
  • [ 1028072-66-3 ]
  • 28
  • [ 147751-16-4 ]
  • [ 1026822-40-1 ]
  • 29
  • [ 147751-16-4 ]
  • C15H19NO4S [ No CAS ]
  • 30
  • [ 147751-16-4 ]
  • C14H19NO5S [ No CAS ]
  • 31
  • [ 147751-16-4 ]
  • C14H19NO4S [ No CAS ]
  • 32
  • [ 147751-16-4 ]
  • C13H16ClNO4S [ No CAS ]
  • 33
  • [ 147751-16-4 ]
  • C13H23NO4S [ No CAS ]
  • 34
  • [ 147751-16-4 ]
  • C13H19N3O6S [ No CAS ]
  • 35
  • [ 147751-16-4 ]
  • C19H29NO4S [ No CAS ]
  • 36
  • [ 147751-16-4 ]
  • C17H20ClN3O4S [ No CAS ]
 

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Technical Information

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