147751-16-4|tert-Butyl methylsulfonylcarbamate| Ambeed

Structure of 147751-16-4

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Quality Control of [ 147751-16-4 ] Purity: 97% SDS Specification

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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
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 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.34
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	0.5
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	1.55
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.	-0.27
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	-0.76
Consensus Log P_o/w? Consensus Log P_o/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 1~55

1
[ 1070-19-5 ]
[ 3144-09-0 ]
[ 147751-16-4 ]

References: [1]Journal of Organic Chemistry,1993,vol. 58,p. 2900 - 2903.

2
[ 4206-67-1 ]
[ 147751-16-4 ]
[ 145387-82-2 ]

References: [1]Journal of Organic Chemistry,1993,vol. 58,p. 2900 - 2903.

3
[ 4206-67-1 ]
[ 147751-16-4 ]
[ 145387-82-2 ]
C₁₄H₃₃NO₄SSi₂ [ No CAS ]

References: [1]Journal of Organic Chemistry,1993,vol. 58,p. 2900 - 2903.

4
[ 3144-09-0 ]
[ 24424-99-5 ]
[ 147751-16-4 ]

Yield	Reaction Conditions	Operation in experiment
83%	With triethylamine;dmap; In dichloromethane; at 25℃; for 2h;	e) Boc-N-(4-Benzylsulfanyl-5-nitro-thiophen-3-ylmethyl)-methanesulfonamide Triethylamine (22.0 mL, 158 mmol), di-tert-butyl dicarbonate (27.5 g, 126 mmol), and 4-(N,N-dimethylamino)pyridine (1.28 g, 10.5 mmol) were added sequentially to a solution of methanesulfonamide (10.0 g, 105 mmol) in dichloromethane (300 mL) at 25 C. The mixture was stirred at 25 C. for 2 h, and then was concentrated in vacuo to ~40 mL volume. Ethyl acetate (350 mL) was added and the mixture was washed with 1.0 M aqueous hydrochloric acid solution (300 mL). The aqueous layer was extracted with ethyl acetate (250 mL) and the combined organic layers were dried over sodium sulfate, filtered and were concentrated in vacuo to afford Boc-N-methanesulfonamide (17.1 g, 87.6 mmol, 83%) as a white solid. 1H NMR (400 MHz, CDCl3) delta: 1.53 (9H, s), 3.27 (3H, s).
81%	With dmap; triethylamine; In dichloromethane; at 20℃; for 3h;	A solution of Boc20 (41.2 g, 189.2 mmol) in DCM (200 mL) was added dropwise to a stirred suspension of methane sulfonamide (15.0 g, 157.7 mmol), Et3N (23.6 mL, 173.5 mmol) and DMAP (1.9 g, 15.8 mmol) in DCM (200 mL). The resulting suspension was stirred for 3 h at room temperature and concentrated under vacuum. The resulting residue was diluted with EtOAc (300 mL) and acidified with 1 N HCI (200 mL). The organic layer was washed with water followed by brine, dried over Na2S04 and concentrated under reduced pressure to obtain a crude mixture, which was triturated with 10% EtOAc in petroleum ether to obtain B1 as a white solid (25.0 g, 81 %). Rf: 0.6 (50% EtOAc in petroleum ether). LCMS m/z = 194.3 (M - H). 1H NMR (400 MHz, CDCI3): delta 1.44 (s, 9H), 3.19 (s, 3H), 7.19 (s, 1 H).
49%	With triethylamine; In dichloromethane; at 20℃;	To a 500 mL row1d bottom f1ask vas added a solution of methanesulfonamide (1 0 g,105.13 mmol, l.OO equiv.) in dichloromeHume (300 mL) follo·wed by TEA (22 g, 217.4120 mmol, 1.50 equiv.), Boc20 (27.5 g, 126.00 mmoL 1.20 equiv.), and 4-dimethylaminopyridine(1.28 g, 10.48 mmol, 0.10 equiv.). The reaction mixture v.·as stirred at room temperatmeovernight and then concentrated under vacuurn. 200 mL ofFhO vvas added, the pFf value of the solution was adjusted to 3 using a 1M hydrogen chloride aqueous solution, and thernixture was extracted with ethyl acetate (200 mL x 3). The combined organic extracts werew·ashed vvith brine (300 mL x 2), dried over anhydrous sodium sulfate and concentratedunder vacuum to give oftert-butyl N-methanesulfonylcarbamate 216b (10.06 g, 49%) as a5 ·white solid.

26.1 g (85%)	With hydrogenchloride; dmap; triethylamine; In hexane; dichloromethane; water; ethyl acetate;	A. N-(t-butoxycarbonyl)methanesulfonamide To a solution of 15.0 g (157.7 mmol) of methanesulfonamide, 17.6 g (173.5 mmol) of triethylamine and 1.9 g (15.8 mmol) of 4-dimethylaminopyridine in 200 mL of dichloromethane was added of 37.9 g (173.5 mmol) of di-t-butyldicarbonate in 200 mL of dichloromethane over ten minutes. The mixture was stirred at ambient temperature for 2.25 hours and concentrated in vacuo. The residue was dissolved in 250 mL of ethyl acetate and washed once with 200 mL of 1 N hydrochloric acid, once with 100 mL of water and once with 100 mL of saturated aqueous sodium chloride. The organic layer was dried (MgSO4), filtered and concentrated in vacuo. The residue was suspended in 100 mL of hexane, filtered and dried in vacuo to afford 26.1 g (85%) of the title compound. Analysis calculated for C7H13NO4S: %C, 36.91; %H, 6.71; %N, 7.17. Found: %C, 36.97; %H, 6.79; %N, 7.04. Mass Spectrum: M+1=196.
		Methanesulfonamide (4.4g; 46.26 mmol), triethylamine (7.1 ml; 50.88 mmol) and DMAP (565 mg; 4.626 mmol) were dissolved in dry CH2CI2 (50 ml) and stirred at room temperature. A solution of di-tert-butyl dicarbonate (1 l.lg; 53.196 mmol) in dry CH2CI2 (100 ml) was slowly added drop by drop over 10 minutes. After the addition was complete the reaction mixture was stirred a further 1 hour, then the volatiles were removed under reduced pressure. The residues were carefully partitioned with 2N hydrochloric acid (150 ml) and diethyl ether (2 x 150 ml). The ether extracts were combined and washed with brine (150 ml) and the extract dried over anhydrous MgSO4 powder, filtered and the filtrates concentrated under reduced pressure. The solid residues obtained from evaporation was triturated with hexanes, the hexane layer was filtered off and discarded. The remaining solid was crystalized from hexane and diethyl ether to give the title compound. 1H-NMR (400 MHz, CDCl3) delta: 1.53 (s, 9H), 3.28 (s.,3H).
	With dmap; triethylamine; In dichloromethane; at 20℃; for 2.5h;	Reference Example 42 To a mixture of methane sulfonamide (1.96 g), triethylamine (3.2 mL), 4-(dimethylamino)pyridine (252 mg), and dichloromethane (30 mL) was added a mixture of di-tert-butyl dicarbonate (5.17 g) and dichloromethane (40 mL) at room temperature for 30 minutes. The mixture was concentrated after stirring for 2 hours, and the residue was distributed with ethyl acetate and 1 N hydrochloric acid. The organic layer was washed with water, dried and concentrated. The obtained residue was purified by silica gel column chromatography to obtain tert-butyl methylsulfonyl carbamate (2.44 g). 1H-NMR (300 MHz, CDCl3) delta: 1.52 (9H, s), 3.28 (3H, s).
	With dmap; triethylamine; In dichloromethane; at 0 - 20℃;	To a stirred suspension of methylsulfonamide (6 g, 62 mmol) in DCM at 0 C. was added DMAP (760 mg, 6.2 mmol), triethylamine (10.4 ml, 74.4 mmol) and (Boc)2O (14.2 g, 65.1 mmol). The reaction mixture was warmed up to room temperature and stirred overnight. The solution was concentrated and the residue was diluted with ethyl acetate, washed consecutively with 1N HCl and water, dried with Na2SO4, filtered and evaporated to afford a colorless oil. The oil was refluxed in hexane for 1 hour then cooled to room temperature and filtered to afford the target compound as a white solid (12.1 g, 42.1% yield). 1H NMR (DMSO-d6, 300 MHz) delta ppm 11.22 (s, 1H), 3.18 (s, 3H), 1.42 (s, 9H).
	With dmap; triethylamine; In dichloromethane; ethyl acetate;	Triethylamine (22.0 mL, 158 mmol), di-tert-butyl dicarbonate (27.5 g, 126 mmol), and 4-(N,N-dimethylamino)pyridine (1.28 g, 10.5 mmol) were added sequentially to a solution of methanesulfonamide (10.0 g, 105 mmol) in dichloromethane (300 mL) at 25 C. The mixture was stirred at 25 C. for 2 h, and then was concentrated in vacuo to ~40 mL volume. Ethyl acetate (350 mL) was added and the mixture was washed with 1.0 M aqueous hydrochloric acid solution (300 mL). The aqueous layer was extracted with ethyl acetate (250 mL) and the combined organic layers were dried over sodium sulfate, filtered and were concentrated in vacuo to afford Boc-N-methanesulfonamide (17.1 g, 87.6 mmol, 83%) as a white solid. 1H NMR (400 MHz, CDCl3) delta: 1.53 (9H, s), 3.27 (3H, s).
1 g	With dmap; triethylamine; In dichloromethane; at 20℃; for 2h;	Triethylamine (2.2 mL, 16 mmol), di-tert-butyldicarbonate (2.65 g, 12.1 mmol) and 4-dimethylaminopyridine (0.096 g, 0.79 mmol) were added sequentially to a solution of methanesulfonamide (0.75 g, 7.9 mmol) in methylene chloride (20 mL) at room temperature. The reaction was stirred at room temperature for 2 h and then concentrated. EtOAc was added, and the resultant mixture was washed with 1N aq. HCl solution, dried over MgSO4 and concentrated to give the desired product (1 g) to be used in the next step directly.
26.1 g (85%)	With hydrogenchloride; dmap; triethylamine; In hexane; dichloromethane; water; ethyl acetate;	A. N-(t-Butoxycarbonyl)Methanesulfonamide: To a solution of 15.0 g (157.7 mmol) of methanesulfonamide, 17.6 g (173.5 mmol) of triethylamine and 1.9 g (15.8 mmol) of 4-dimethylaminopyridine in 200 mL of dichloromethane was added of 27.9 g (173.5 mmol) of di-t-butyldicarbonate in 200 mL of dichloromethane over ten minutes. The mixture was stirred at ambient temperature for 2.25 hours and concentrated in vacuo. The residue was dissolved in 250 mL of ethyl acetate and washed once with 200 mL of 1 N hydrochloric acid, once with 100 mL of water and once with 100 mL of saturated aqueous sodium chloride. The organic layer was dried (MgSO4), filtered and concentrated in vacuo. The residue was suspended in 100 mL of hexane, filtered and dried in vacuo to afford 26.1 g (85%) of the title compound. Analysis calculated for C7H13NO4S: %C, 36.91; %H, 6.71; %N, 7.17. Found: %C, 36.97; %H, 6.79; %N, 7.04. Mass Spectrum: M+1=196.

References: [1]Tetrahedron Letters,1994,vol. 35,p. 379 - 380.
[2]Patent: US2009/306057,2009,A1 .Location in patent: Page/Page column 44.
[3]Journal of the American Chemical Society,2015,vol. 137,p. 5638 - 5641.
[4]Journal of Organic Chemistry,2006,vol. 71,p. 8283 - 8286.
[5]Organic Letters,2006,vol. 8,p. 4707 - 4710.
[6]Patent: WO2015/181676,2015,A1 .Location in patent: Page/Page column 136-137.
[7]Organic Letters,2020,vol. 22,p. 1659 - 1664.
[8]Patent: WO2018/39386,2018,A1 .Location in patent: Page/Page column 356; 357.
[9]Patent: US6303816,2001,B1 .
[10]Patent: WO2008/85300,2008,A1 .Location in patent: Page/Page column 85.
[11]Patent: EP1553074,2005,A1 .Location in patent: Page/Page column 44.
[12]Patent: US2010/256092,2010,A1 .Location in patent: Page/Page column 109.
[13]Patent: US2012/316156,2012,A1 .
[14]Patent: US2014/121198,2014,A1 .Location in patent: Paragraph 0642; 0643.
[15]Patent: US6387954,2002,B1 .
[16]European Journal of Medicinal Chemistry,2019,vol. 174,p. 252 - 264.
[17]Green Chemistry,2020,vol. 22,p. 1113 - 1118.

5
[ 75-21-8 ]
[ 147751-16-4 ]
tert-butyl N-[(3-hydroxypropyl)sulfonyl]carbamate [ No CAS ]

References: [1]Tetrahedron,2006,vol. 62,p. 1799 - 1805.

6
[ 96-09-3 ]
[ 147751-16-4 ]
tert-butyl N-[(3-hydroxy-3-phenylpropyl)sulfonyl]carbamate [ No CAS ]

References: [1]Tetrahedron,2006,vol. 62,p. 1799 - 1805.
[2]Organic Letters,2015,vol. 17,p. 190 - 193.
[3]Tetrahedron Letters,2017,vol. 58,p. 1528 - 1530.

7
[ 147751-16-4 ]
[ 75-56-9 ]
tert-butyl N-[(3-hydroxybutane)sulfonyl]carbamate [ No CAS ]

Yield	Reaction Conditions	Operation 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

References: [1]Tetrahedron,2006,vol. 62,p. 1799 - 1805.
[2]Patent: WO2015/181676,2015,A1 .Location in patent: Page/Page column 137.
[3]Patent: WO2018/39386,2018,A1 .Location in patent: Page/Page column 356; 357.
[4]Tetrahedron Letters,2017,vol. 58,p. 1528 - 1530.
[5]Patent: WO2018/11163,2018,A1 .Location in patent: Page/Page column 26; 27.

8
[ 27701-23-1 ]
[ 147751-16-4 ]
[ 914801-93-7 ]

Yield	Reaction Conditions	Operation 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).

References: [1]Organic Letters,2006,vol. 8,p. 4707 - 4710.
[2]Patent: US2008/293666,2008,A1 .Location in patent: Page/Page column 40.

9
[ 1002761-79-6 ]
[ 147751-16-4 ]
[ 1002761-80-9 ]

Yield	Reaction Conditions	Operation 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).

References: [1]Patent: WO2008/11337,2008,A1 .Location in patent: Page/Page column 49.

10
[ 686271-29-4 ]
[ 147751-16-4 ]
[ 1002761-80-9 ]

Yield	Reaction Conditions	Operation 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.

References: [1]Patent: US2009/306057,2009,A1 .Location in patent: Page/Page column 39; 44.
[2]Patent: WO2008/11337,2008,A1 .Location in patent: Page/Page column 49-50.

11
[ 147751-16-4 ]
[ 2984-50-1 ]
[ 942066-37-7 ]

References: [1]Journal of Organic Chemistry,2007,vol. 72,p. 3729 - 3734.
[2]Tetrahedron Letters,2017,vol. 58,p. 1528 - 1530.

12
[ 5234-06-0 ]
[ 147751-16-4 ]
[ 942066-42-4 ]

References: [1]Journal of Organic Chemistry,2007,vol. 72,p. 3729 - 3734.
[2]Organic Letters,2015,vol. 17,p. 190 - 193.
[3]Tetrahedron Letters,2017,vol. 58,p. 1528 - 1530.

13
[ 2930-05-4 ]
[ 147751-16-4 ]
[ 942066-43-5 ]

References: [1]Journal of Organic Chemistry,2007,vol. 72,p. 3729 - 3734.
[2]Tetrahedron Letters,2017,vol. 58,p. 1528 - 1530.

14
[ 122-60-1 ]
[ 147751-16-4 ]
[ 942066-38-8 ]

References: [1]Journal of Organic Chemistry,2007,vol. 72,p. 3729 - 3734.
[2]Organic Letters,2015,vol. 17,p. 190 - 193.
[3]Tetrahedron Letters,2017,vol. 58,p. 1528 - 1530.

15
[ 2186-24-5 ]
[ 147751-16-4 ]
[ 942066-40-2 ]

References: [1]Journal of Organic Chemistry,2007,vol. 72,p. 3729 - 3734.
[2]Organic Letters,2015,vol. 17,p. 190 - 193.
[3]Tetrahedron Letters,2017,vol. 58,p. 1528 - 1530.

16
[ 2210-79-9 ]
[ 147751-16-4 ]
[ 942066-41-3 ]

References: [1]Journal of Organic Chemistry,2007,vol. 72,p. 3729 - 3734.
[2]Organic Letters,2015,vol. 17,p. 190 - 193.
[3]Tetrahedron Letters,2017,vol. 58,p. 1528 - 1530.

17
[ 198226-65-2 ]
[ 147751-16-4 ]
[ 942066-39-9 ]

References: [1]Journal of Organic Chemistry,2007,vol. 72,p. 3729 - 3734.

18
[ 147751-16-4 ]
C₁₆H₂₃NO₆S [ No CAS ]

References: [1]Journal of Organic Chemistry,2007,vol. 72,p. 3729 - 3734.

19
[ 147751-16-4 ]
C₁₀H₁₈NO₄SC₄H₉O [ No CAS ]

References: [1]Journal of Organic Chemistry,2007,vol. 72,p. 3729 - 3734.

20
[ 147751-16-4 ]
C₁₅H₂₁NO₆S [ No CAS ]

References: [1]Journal of Organic Chemistry,2007,vol. 72,p. 3729 - 3734.
[2]Organic Letters,2015,vol. 17,p. 190 - 193.

21
[ 147751-16-4 ]
C₁₆H₂₃NO₆S [ No CAS ]

References: [1]Journal of Organic Chemistry,2007,vol. 72,p. 3729 - 3734.
[2]Organic Letters,2015,vol. 17,p. 190 - 193.

22
[ 147751-16-4 ]
C₁₆H₂₃NO₆S [ No CAS ]

References: [1]Journal of Organic Chemistry,2007,vol. 72,p. 3729 - 3734.
[2]Organic Letters,2015,vol. 17,p. 190 - 193.

23
[ 147751-16-4 ]
[ 914801-94-8 ]

References: [1]Organic Letters,2006,vol. 8,p. 4707 - 4710.

24
[ 147751-16-4 ]
[ 914801-95-9 ]

References: [1]Organic Letters,2006,vol. 8,p. 4707 - 4710.

25
[ 147751-16-4 ]
[ 881652-42-2 ]

References: [1]Tetrahedron,2006,vol. 62,p. 1799 - 1805.

26
[ 147751-16-4 ]
[ 881652-43-3 ]

References: [1]Tetrahedron,2006,vol. 62,p. 1799 - 1805.
[2]Patent: WO2015/181676,2015,A1 .
[3]Tetrahedron Letters,2017,vol. 58,p. 1528 - 1530.
[4]Patent: WO2018/11163,2018,A1 .

27
[ 147751-16-4 ]
tert-butyl N-[(3-oxo-3-phenylpropyl)sulfonyl]carbamate [ No CAS ]

References: [1]Tetrahedron,2006,vol. 62,p. 1799 - 1805.
[2]Organic Letters,2015,vol. 17,p. 190 - 193.

28
[ 147751-16-4 ]
[ 206198-17-6 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 809 - 812.

29
[ 147751-16-4 ]
C₃₂H₄₂N₂O₉S [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 809 - 812.

30
[ 147751-16-4 ]
C₁₁H₁₅NO₅S [ No CAS ]