Name: 1709-52-0|4-Amino-N-methylbenzenesulfonamide|98%
Brand: Ambeed
SKU: A491525
Price: 12.0 USD
Availability: InStock
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1
[ 112-77-6 ]
[ 1709-52-0 ]
N-oleoyl-sulfanilic acid methylamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine

Reference： [1]Current Patent Assignee: I.G. FARBENINDUSTRIE AG (historic) - CH201207, 1937, A

2
[ 97-65-4 ]
[ 1709-52-0 ]
1-(4-methylsulfamoyl-phenyl)-5-oxo-pyrrolidine-3-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	bei laengerem Erhitzen;

Reference： [1]Paytash et al. [Journal of the American Chemical Society, 1952, vol. 74, p. 4549]

3
[ 6884-87-3 ]
[ 1709-52-0 ]

Yield	Reaction Conditions	Operation in experiment
75%	With water; potassium hydroxide In methanol at 65℃; for 24h;	4.1.12 General procedure for deprotection of the amino group General procedure: A solution of potassium hydroxide (1.62g, 28.89mmol) in 5mL water was slowly added to a solution of the corresponding acetamide intermediate (4mmol) in 25mL methanol. The reaction mixture was stirred and heated at 65°C for 24h. Completion of the reaction was verified by TLC. The aniline derivative was isolated by concentration at reduced pressure followed by filtration of the precipitate through a Büchner funnel.
48%	With hydrogenchloride; water In methanol for 1h; Reflux;	4.2.3. Sulfanilic Acid N-Methyl Amide (IIa) 12 mL of concentrated HCl were added to a suspension of 5.50 g (24.12 mmol) Ia in 40 mL ofMeOH and were refluxed for 1 h in a flask equipped with a reflux condenser. After the end of the reaction, the reaction mixture was poured into 250 mL of 10% NaHCO3 in H2O. The precipitate wasseparated, washed with 200 mL H2O and dried in vacuum under KOH.
	With hydrogenchloride

Reference： [1]Barbosa, Maria Letícia De Castro; Lima, Lídia Moreira; Tesch, Roberta; Sant'Anna, Carlos Mauricio R.; Totzke, Frank; Kubbutat, Michael H.G.; Schächtele, Christoph; Laufer, Stefan A.; Barreiro, Eliezer J. [European Journal of Medicinal Chemistry, 2014, vol. 71, p. 1 - 14]
[2]Ilizirov, Yana; Formanovsky, Andrei; Mikhura, Irina; Paitan, Yossi; Nakonechny, Faina; Nisnevitch, Marina [Molecules, 2018, vol. 23, # 12]
[3]Mangini [Atti della Accademia Nazionale dei Lincei, Classe di Scienze Fisiche, Matematiche e Naturali, Rendiconti, 1940, vol. <7> 1, p. 452,457] Andrewes; King; Walker [Proceedings of the Royal Society of London. Series B, Biological sciences, 1946, vol. 133, p. 20,30]

4
[ 1709-52-0 ]
[ 17243-13-9 ]
2-hydroxy-5-(4-methylsulfamoyl-phenylsulfamoyl)-benzoic acid [ No CAS ]

Reference： [1]Patent: US2256274,1939,

5
[ 1709-52-0 ]
[ 98-88-4 ]
N-(4-(N-methylsulfamoyl)phenyl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine

Reference： [1]Mangini [Bollettino Scientifico della Facolta di Chimica Industriale di Bologna, 1940, vol. 1, p. 143]

6
[ 1709-52-0 ]
[ 79-22-1 ]
N-methoxycarbonyl-sulfanilic acid methylamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; acetone

Reference： [1]Current Patent Assignee: I.G. Farbenind. - DE750740, 1936, C [DRP/DRBP Org.Chem.][DRP/DRBP Org.Chem.]

7
[ 1709-52-0 ]
[ 1885-14-9 ]
N-phenoxycarbonyl-sulfanilic acid methylamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; acetone

Reference： [1]Current Patent Assignee: I.G. Farbenind. - DE750740, 1936, C [DRP/DRBP Org.Chem.][DRP/DRBP Org.Chem.]

8
[ 1709-52-0 ]
[ 814-68-6 ]
[ 146447-87-2 ]

Reference： [1]Current Patent Assignee: EASTMAN KODAK CO - US2566162, 1950, A

9
[ 1709-52-0 ]
[ 121-60-8 ]
[ 71119-14-7 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate; acetone

Reference： [1]Current Patent Assignee: WINTHROP CHEM - US2289029, 1937, A Current Patent Assignee: I.G. FARBENINDUSTRIE AG (historic) - DE686903, 1936, C [DRP/DRBP Org.Chem.][DRP/DRBP Org.Chem.]

10
[ 1709-52-0 ]
[ 1147550-11-5 ]
[ 18101-53-6 ]

Yield	Reaction Conditions	Operation in experiment
	With bromine In acetic acid

Reference： [1]Pohloudek-Fabini,R.; Schuessler,M. [Pharmazie, 1967, vol. 22, p. 620 - 624]

11
[ 2782-91-4 ]
[ 1709-52-0 ]
C₁₂H₂₀N₃O₂S₂⁽¹⁺⁾*ClO₄^(1-) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	1.) diazotization; Yield given. Multistep reaction;

Reference： [1]Tait; Giovannini; Di Bella; Bondi; Quaglio [Farmaco, Edizione Scientifica, 1988, vol. 43, # 12, p. 979 - 988]

12
[ 1709-52-0 ]
[ 155457-59-3 ]
N-methyl-4-<(3,6-dipropionamido-9-acridinyl)amino>benzenesulfonamide hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
32%	In various solvent(s) at 20℃; for 3h;

Reference： [1]Gamage, Swarna A.; Tepsiri, Nisana; Wilairat, Prapon; Wojcik, Stanley J.; Figgitt, David P.; et al. [Journal of Medicinal Chemistry, 1994, vol. 37, # 10, p. 1486 - 1494]

13
[ 1709-52-0 ]
[ 111-36-4 ]
[ 91637-06-8 ]

Yield	Reaction Conditions	Operation in experiment
	In 1,4-dioxane

Reference： [1]HAYMAN; PETROW; STEPHENSON [Journal of Pharmacy and Pharmacology, 1962, vol. 14, p. 522 - 533]

14
[ 19602-82-5 ]
[ 1709-52-0 ]
C₂₈H₂₆N₄O₆S₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
46%	With pyridine In dichloromethane at 0 - 23℃; for 18h;

Reference： [1]Domagala, John M.; Bader, John P.; Gogliotti, Rocco D.; Sanchez, Joseph P.; Stier, Michael A.; Song, Yuntao; Vara Prasad; Tummino, Peter J.; Scholten, Jeffrey; Harvey, Patricia; Holler, Tod; Gracheck, Steve; Hupe, Donald; Rice, William G.; Schultz, Robert [Bioorganic and Medicinal Chemistry, 1997, vol. 5, # 3, p. 569 - 579]

15
[ 6319-45-5 ]
[ 1709-52-0 ]

Yield	Reaction Conditions	Operation in experiment
100%	With hydrogen In methanol at 25℃; for 20h;
98%	With hydrogen In methanol for 2h;
97.1%	With hydrazine hydrate In isopropyl alcohol at 60℃; for 8h;	4 Example 4 To 150 ml four-necked flask equipped with a stirrer, a thermometer, and a reflux condenser was added 10 g of 4-nitro-N-methylbenzenesulfonamide, 64 g of isopropyl alcohol and 2 g of Ra-Ni. The temperature was increased to 60 deg.C. Add dropwise 10 g of 80% hydrazine hydrate. After 1 hour, dropping is complete. Continue at 60 deg.C and stir for 7 hours. After the reaction is complete, cool to 10 deg.C, filter, the filter cake was washed with a small amount of isopropyl alcohol and vacuum dried at 60 deg.C to obtain 8.6 g of a pale yellow solid, and the content of the chemical analysis was 98.2%. And the yield was 97.1%.

90%	With hydrazine In ethanol	1.7 Preparation 7: Synthesis of 4-amino-N-methylbenzenesulfonamide To an ice cold solution of 4-nitrobenzenesulfonyl chloride (2.7 g, 12 mmol) and triethylamine (27 mmol) in 60 mL of dry THF was added methylamine (8 mL of a 2 M solution in THF, 16 [MMOL).] The mixture was stirred at room temperature overnight. Brine was added and the reaction solution was extracted with ethyl acetate. The combined organic extracts were dried over sodium sulfate, filtered, and evaporated to yield 4-nitrobenzenesulfonic acid methylamide as an oil. The crude material was used in the subsequent reaction without further purification. To a solution of the crude 4-nitrobenzenesulfonyl methylamide prepared above in 45 mL of ethanol, was added a 1 mL slurry of Raney Nickel. Hydrazine monohydrate (18 mmol) was added slowly in several portions. A change in the solution colour from yellow to colourless indicated the reaction was complete. The mixture was stirred for an additional 1 hr. The solids were removed by filtration and the solvent was evaporated. The resulting crude material was purified by flash column chromatography eluting with [CH2CI2 : MEOH] = 10: 1 to yield 2.09 g (90% for two steps) of the title compound as a pale orange powder.
84%	With sodium tetrahydroborate; nickel(II) chloride hexahydrate In tetrahydrofuran; methanol at 0℃; for 0.333333h;
84.5%	With palladium on activated charcoal; hydrogen In isopropyl alcohol at 20℃;	2 2. Synthesis of 4-amino-N-methylbenzene-l-sulfonamide Into a 250 mL round-bottom flask were added N-methyl-4-nitrobenzene-1-sulfonamide (5.8 g, 26.8 mmol, 1 equiv) and isopropanol (50 mL) at room temperature. To a stirred solution of N-methyl-4-nitrobenzene-1-sulfonamide (5.8 g, 26.8 mmol, 1 equiv) in isopropanol (50 mL) was added Pd/C (580 mg, 5.5 mmol, 0.20 equiv) at room temperature under nitrogen. The resulting mixture was stirred overnight at room temperature under hydrogen atmosphere, and was then filtered. The filtrate was concentrated under reduced pressure to affored 4-amino-N-methylbenzene-1-sulfonamide (4.9 g, 84.5%) as yellow solid. LCMS of 4-amino-N-methylbenzene-1-sulfonamide (Method B): 187 [M+H]+, retention time 0.625 min.
84.5%	With palladium on activated charcoal; hydrogen In isopropyl alcohol at 20℃;	A.2 Synthesis of 4-amino-N-methylbenzene-l-sulfonamide Into a 250 mL round-bottom flask was added N-methyl-4-nitrobenzene-l-sulfonamide(5.8 g, 26.8 mmol, 1 equiv) and isopropanol(50 mL) at room temperature. To the stirred solution was added Pd/C(580 mg, 5.5 mmol, 0.20 equiv) at room temperature under nitrogen. The resulting mixture was stirred overnight at room temperature under hydrogen atmosphere, after which it was filtered to remove the solid. The filtrate was concentrated under reduced pressure to afford 4-amino-N-methylbenzene-l -sulfonamide (4.9 g, 84.5%) as yellow solid.
80%	With palladium on activated charcoal; hydrogen In methanol at 20℃; for 12h;	To a solution of compound 27-2 (3.3 g, 15.3 mol) in CH3OH (50 mL) was added Pd/C (0.16 g) at room temperature. The mixture was stirred under H2 (30 psi) at room temperature for 12 h. The mixture was filtered and the solvent was removed to give the compound 27-3 (2.3 g, yield: 80%) as a gray solid.
71%	With hydrogen In methanol; N,N-dimethyl-formamide at 20℃; for 72h;	b A mixture of -V-methyl-4-nitrobenzenesulfonamide (337 mg, 1.56 mmol), Pd-C (10% Pd, 100 mg) and a few drops of DMF in MeOH (20 mL) was hydrogenated at normal pressure and temperature for 3 days. The mixture was filtered through Celite and concentrated to give the title product (207 mg, 71 %) as brown crystals.1H NMR (DMSO-J6, 400 MHz) δ 7.40 (2H, ddd), 6.90 (IH, q), 6.61 (2H} ddd), 5.91 (2H, s), 2.32 (3H5 d).
	With hydrogen In methanol at 20℃; for 18h;	42.2 Step 2: Synthesis of 4-amino-N-methylbenzenesulfonamide (3): [000277j To a stirred solution of compound 2 (0.8 g, leq) in methanol (20 mL), Raney nickel (1 g) was added and stirred at room temperature for 18 h under hydrogen atmosphere. The progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was filtered and evaporated under reduced pressure to afford the title compound 3. LCMS (mlz): 187.00 (M + 1).

Reference： [1]Khanna, Ish K.; Weier, Richard M.; Yu, Yi; Collins, Paul W.; Miyashiro, Julie M.; Koboldt, Carol M.; Veenhuizen, Amy W.; Currie, Jerry L.; Seibert, Karen; Isakson, Peter C. [Journal of Medicinal Chemistry, 1997, vol. 40, # 11, p. 1619 - 1633]
[2]Current Patent Assignee: PFIZER INC - EP1215208, 2002, A2 Location in patent: Example C(108)
[3]Current Patent Assignee: QINGDAO HUANGDAO DISTR CHINESE MEDICINE HOSPITAL - CN105732443, 2016, A Location in patent: Paragraph 0022; 0023
[4]Current Patent Assignee: ELI LILLY & CO - WO2004/11460, 2004, A2 Location in patent: Page 58-59
[5]Location in patent: experimental part Lawrence, Harshani R.; Kazi, Aslamuzzaman; Luo, Yunting; Kendig, Robert; Ge, Yiyu; Jain, Sanjula; Daniel, Kenyon; Santiago, Daniel; Guida, Wayne C.; Sebti, Said M. [Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 15, p. 5576 - 5592]
[6]Current Patent Assignee: Novartis (w/o Sandoz); NOVARTIS AG - WO2020/10140, 2020, A1 Location in patent: Page/Page column 337; 338
[7]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - WO2020/10143, 2020, A1 Location in patent: Page/Page column 346; 352-353
[8]Current Patent Assignee: SCRIPPS RESEARCH - US2014/271955, 2014, A1 Location in patent: Paragraph 0749
[9]Current Patent Assignee: OREXO AB - WO2007/51982, 2007, A1 Location in patent: Page/Page column 41
[10]Current Patent Assignee: BIOMARIN PHARMACEUTICAL INC - WO2016/57834, 2016, A1 Location in patent: Paragraph 000277

16
[ 1709-52-0 ]
[ 189501-42-6 ]
4-[2-(4-fluorophenyl)-1H-pyrrol-1-yl]-N-methylbenzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40%	With toluene-4-sulfonic acid In toluene for 20h; Ambient temperature;
40%	With toluene-4-sulfonic acid In toluene	76.7 Preparation of 4-[2-(4-fluorophenyl)-1H-pyrrol-1-yl]-N-methylbenzenesulfonamide Step 7 Preparation of 4-[2-(4-fluorophenyl)-1H-pyrrol-1-yl]-N-methylbenzenesulfonamide A mixture of 3-(5,5-dimethyl-1,3-dioxan-2-yl)-1-(4-fluorophenyl)propan-1-one (Step 4) (400 mg, 1.5 mmol), 4-[(N-methylamino)sulfonyl]aniline (Step 6) (308 mg, 1.65 mmol) and p-toluenesulfonic acid (40 mg) in toluene (80 ml) was heated to reflux for 48 hr. The reaction mixture was cooled, filtered and concentrated. The crude yellowish solid (760 mg) was chromatographed (silica gel, hexane/ethyl acetate 7/3) to give 4-[2-(4-fluorophenyl)-1H-pyrrol-1-yl]-N-methylbenzenesulfonamide (198 mg, 40%) as a white solid: mp (DSC) 174° C. Anal Calc'd. for C17 H15 N2 FO2 S 0.25 H2 O: C, 60.97; H, 4.67; N, 8.37. Found: C, 60.86; H, 4.56; N, 8.01.

Reference： [1]Khanna, Ish K.; Weier, Richard M.; Yu, Yi; Collins, Paul W.; Miyashiro, Julie M.; Koboldt, Carol M.; Veenhuizen, Amy W.; Currie, Jerry L.; Seibert, Karen; Isakson, Peter C. [Journal of Medicinal Chemistry, 1997, vol. 40, # 11, p. 1619 - 1633]
[2]Current Patent Assignee: PFIZER INC - US5932598, 1999, A

Yield	Reaction Conditions	Operation in experiment
	at 180℃; Bei kurzem Erhitzen;

Yield	Reaction Conditions	Operation in experiment
87%	With hydrogenchloride; palladium 10% on activated carbon; hydrogen In ethanol; water	11 Preparation of 3-benzylaminesulfonamide derivatives General procedure: To a stirred solution of 3-cyanobenzenesulfonylamide derivative (1 equiv.) in absolute ethanol (4 mL/mmol) and cone. HCI (0.4 mL/mmol), 10% palladium on carbon (-20 wt %) was added under azote atmosphere.Hydrogen gas was bubbled through the reaction mixture for 10 min and the mixture was stirred overnight under hydrogen atmosphere until completion. The mixture was passed through a plug of celite and the solvent was removed under reduced pressure. Purification by flash column chromatography (0-10% MeOH in DCM + 2% NH4OH) yielded the expected compound.The following compounds are examples illustrating this procedure:; N-benzyl-4-amino-benzenesulfonamide was prepared from N-benzyl-4-cyano- benzenesulfonamide (817 mg, 3 mmol). Yield: 602 mg (73 %) of the title compound as a white powder. 1 H NMR (300 MHz, DMSO-ck) δ 8.49 (bs, 2H), 7.94-7.92 (m, 1 H), 7.79-7.77 (m, 2H), 7.68-7.65 (m, 2H), 7.59-7.56 (m, 1 H), 4.12 (s, 2H), 2.43 (d, J = 4.8 Hz, 3H).
	Na-Verb. v. Sulfanilamid, 4,6-Dimethoxy-pyrimidin (Acetamid, 2h 155-160grad);
	(yield)ca.40percent;

	NH2-PhSO2Cl, MeNH2*HCl;
	4-Acetamino-benzolsulfonsaeure-methylamid, sd.50percentig.HCl, dann Na2CO3;

19
[ 860425-08-7 ]
[ 1709-52-0 ]

Reference： [1]Picard et al. [Journal of the Chemical Society, 1946, p. 751]

20
[ 1709-52-0 ]
N-(3,4-dimethoxy-benzenesulfonyl)-sulfanilic acid methylamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate; acetone

Reference： [1]Current Patent Assignee: WINTHROP CHEM - US2289029, 1937, A

21
[ 1709-52-0 ]
3-(ethoxymethylene)-1,3-dihydro-2H-indol-2-one [ No CAS ]
N-methyl-4-[(2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]amino}benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol for 18h; Heating;

Reference： [1]Bramson; Holmes; Hunter; Lackey; Lovejoy; Luzzio; Montana; Rocque; Rusnak; Shewchuk; Veal; Corona; Walker; Kuyper; Davis; Dickerson; Edelstein; Frye; Gampe Jr.; Harris; Hassell [Journal of Medicinal Chemistry, 2001, vol. 44, # 25, p. 4339 - 4358]

22
[ 1709-52-0 ]
[ 222036-33-1 ]
N-methyl-4-[(7-oxo-6,7-dihydro-8H-[1,3]thiazolo[5,4-e]indol-8-ylidene)methyl]amino}benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol for 18h; Heating;

Reference： [1]Bramson; Holmes; Hunter; Lackey; Lovejoy; Luzzio; Montana; Rocque; Rusnak; Shewchuk; Veal; Corona; Walker; Kuyper; Davis; Dickerson; Edelstein; Frye; Gampe Jr.; Harris; Hassell [Journal of Medicinal Chemistry, 2001, vol. 44, # 25, p. 4339 - 4358]

23
[ 1709-52-0 ]
[ 105893-07-0 ]
2,2'-diselenobis{benz[p-(N-methylsulfonamido)]anilide} [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58%	With pyridine In toluene Heating;

Reference： [1]Palus; Kloc; Mllochowski; Mallysa; Szczurek; Piasecki; Rybka [Polish Journal of Chemistry, 2001, vol. 75, # 5, p. 657 - 662]

24
[ 1709-52-0 ]
[ 444723-30-2 ]
NU 6127 [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
27%	With trifluoroacetic acid In butan-1-ol for 48h; Heating;

Reference： [1]Hardcastle, Ian R; Arris, Christine E; Bentley, Johanne; Boyle, F Thomas; Chen, Yuzhu; Curtin, Nicola J; Endicott, Jane A; Gibson, Ashleigh E; Golding, Bernard T; Griffin, Roger J; Jewsbury, Philip; Menyerol, Jerome; Mesguiche, Veronique; Newell, David R; Noble, Martin E M; Pratt, David J; Wang, Lan-Zhen; Whitfield, Hayley J [Journal of medicinal chemistry, 2004, vol. 47, # 15, p. 3710 - 3722]

25
[ 1709-52-0 ]
[ 328062-35-7 ]
2-[4-(N-methylsulphamoyl)anilino]-4-(imidazo[1,2-a]pyrid-3-yl)pyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
15mg, (60%)	With sodium t-butanolate In toluene at 100℃; for 3h;	39 2-[4-(N-Methylsulphamoyl)anilino]-4-(imidazo(1,2a]pyrid-3-yl)pyrimidine Example 39 2-[4-(N-Methylsulphamoyl)anilino]-4-(imidazo(1,2a]pyrid-3-yl)pyrimidine Toluene (4ml) was added to a mixture of tris(dibenzideneacetone)dipalladium(0) (24mg, 0.026mmol), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (21mg, 0.034mmol), 2-chloro-4-(imidazo[ 1,2a]pyrid-3-yl)pyrimidine (Method 20; 150mg, 0.652mmol) and 4-(N-methylsulphamoyl)aniline (Method 23; 135mg, 0.725mmol) under nitrogen. The flask was evacuated and refilled with nitrogen and sodium tert-butoxide (140mg, 1.46mmol) was added and the flask was re-evacuated and refilled with nitrogen. The mixture was heated at 100°C for 3 hours and then allowed to cool. The mixture was diluted with ethyl acetate and washed with water. The organic phase was separated, dried and the volatiles removed by evaporation. The residue was purified by chromatography eluding with ethyl acetate / methanol (100:0 increasing in polarity to 97:3) to give the title compound 15mg, (60%). NMR: 2.42 (d, 3H), 7.25-7.10 (m, 2H), 7.52-7.45 (m, 2H), 7.79-7.70 (m, 3H), 7.98 (d, 2H), 8.50 (d, 1H), 8.62 (s, 1H); m/z: 381 [MH]+.

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - EP1214318, 2003, B1 Location in patent: Page/Page column 23

26
[ 98-74-8 ]
[ 1709-52-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 98 percent / diethyl ether; H₂O / 16 h / Ambient temperature 2: 100 percent / H₂ / Raney-Ni / methanol / 20 h / 25 °C / 258.6 Torr
	Multi-step reaction with 2 steps 1: dichloromethane / 2 h / 20 °C 2: palladium on activated charcoal; hydrogen / methanol / 12 h / 20 °C / 1551.49 Torr
	Multi-step reaction with 2 steps 1: tetrahydrofuran / 6 h / 0 - 20 °C 2: hydrogen / methanol / 18 h / 20 °C

	Multi-step reaction with 2 steps 1: 1 h / 0 - 20 °C 2: hydrogen; palladium on activated charcoal / isopropyl alcohol / 20 °C
	Multi-step reaction with 2 steps 1: 1 h / 0 - 20 °C 2: palladium on activated charcoal; hydrogen / isopropyl alcohol / 20 °C

Reference： [1]Khanna, Ish K.; Weier, Richard M.; Yu, Yi; Collins, Paul W.; Miyashiro, Julie M.; Koboldt, Carol M.; Veenhuizen, Amy W.; Currie, Jerry L.; Seibert, Karen; Isakson, Peter C. [Journal of Medicinal Chemistry, 1997, vol. 40, # 11, p. 1619 - 1633]
[2]Current Patent Assignee: SCRIPPS RESEARCH - US2014/271955, 2014, A1
[3]Current Patent Assignee: BIOMARIN PHARMACEUTICAL INC - WO2016/57834, 2016, A1
[4]Current Patent Assignee: Novartis (w/o Sandoz); NOVARTIS AG - WO2020/10140, 2020, A1
[5]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - WO2020/10143, 2020, A1

27
[ 1709-52-0 ]
4-mercapto-N-methyl-benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 1.) diazotization 2: 2percent aq. NaOH / Ambient temperature

Reference： [1]Tait; Giovannini; Di Bella; Bondi; Quaglio [Farmaco, Edizione Scientifica, 1988, vol. 43, # 12, p. 979 - 988]

28
[ 1709-52-0 ]
[ 917761-25-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 1.) diazotization 2: 2percent aq. NaOH / Ambient temperature

Reference： [1]Tait; Giovannini; Di Bella; Bondi; Quaglio [Farmaco, Edizione Scientifica, 1988, vol. 43, # 12, p. 979 - 988]

29
[ 1709-52-0 ]
[ 547-53-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: sodium hydrogencarbonate; acetone 2: aqueous hydrochloric acid

Reference： [1]Current Patent Assignee: WINTHROP CHEM - US2289029, 1937, A Current Patent Assignee: I.G. FARBENINDUSTRIE AG (historic) - DE686903, 1936, C [DRP/DRBP Org.Chem.][DRP/DRBP Org.Chem.]

30
[ 121-60-8 ]
[ 1709-52-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: ethanol; diethyl ether 2: aqueous hydrochloric acid
	Multi-step reaction with 2 steps 1: water 2: aqueous hydrochloric acid
	Multi-step reaction with 2 steps 1: dichloromethane; tetrahydrofuran / 0.5 h / 20 °C 2: potassium hydroxide; water / methanol / 24 h / 65 °C

Multi-step reaction with 2 steps 1: sodium carbonate / water / 3 h / 0 - 80 °C 2: hydrogenchloride; water / methanol / 1 h / Reflux

Reference： [1]Andrewes; King; Walker [Proceedings of the Royal Society of London. Series B, Biological sciences, 1946, vol. 133, p. 20,30]
[2]Mangini [Atti della Accademia Nazionale dei Lincei, Classe di Scienze Fisiche, Matematiche e Naturali, Rendiconti, 1940, vol. <7> 1, p. 452,457]
[3]Barbosa, Maria Letícia De Castro; Lima, Lídia Moreira; Tesch, Roberta; Sant'Anna, Carlos Mauricio R.; Totzke, Frank; Kubbutat, Michael H.G.; Schächtele, Christoph; Laufer, Stefan A.; Barreiro, Eliezer J. [European Journal of Medicinal Chemistry, 2014, vol. 71, p. 1 - 14]
[4]Ilizirov, Yana; Formanovsky, Andrei; Mikhura, Irina; Paitan, Yossi; Nakonechny, Faina; Nisnevitch, Marina [Molecules, 2018, vol. 23, # 12]

31
[ 463-71-8 ]
[ 1709-52-0 ]
[ 223785-90-8 ]

Yield	Reaction Conditions	Operation in experiment
87%	With calcium carbonate In dichloromethane; water at 0 - 20℃; Inert atmosphere;	22 4-isothiocyanato-N-methylbenzenesulfonamide To a suspension of calcium carbonate (1.34 g, 13.4 mmol, Eq: 2.5) and thiophosgene (679 mg, 453 μ, 5.91 mmol, Eq: 1.1) in dichloromethane (13.2 g, 10.0 ml, 155 mmol, Eq: 28.9)/water (10.0 g, 10.0 ml, 555 mmol, Eq: 103) at 0, was added 4-amino-N- methylbenzenesulfonamide (1 g, 5.37 mmol, Eq: 1.00). The reaction was gradually warmed to room temperature. Added IN HCl slowly. Separated organic layer and dried over sodium sulfate to give 1.064 g (87%) of desired product as a white solid.
79%

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - WO2014/6066, 2014, A1 Location in patent: Paragraph 0202
[2]Current Patent Assignee: PFIZER INC - EP1215208, 2002, A2 Location in patent: Example C(108)

32
[ 1709-52-0 ]
[ 18101-58-1 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: N-methyl-4-aminobenzenesulfonamide With ammonium thiocyanate In acetic acid at 20℃; for 0.5h; Stage #2: With bromine In acetic acid at 20℃; for 64h; Stage #3: With sodium hydrogencarbonate In water	1.9.1 Preparation 9: Synthesis of 2-cyanomethylbenzothiazole-6-sulfonic acid amide 1. To a suspension of 4-amino-N-methylbenzenesulfonamide (43 g, 250 mmol) in 400 mL acetic acid was added ammonium thiocyanate (49 g, 650 mmol) in several portions. After the mixture had been stirred at room temperature for 30 min, a solution of bromine (13 mL, 250 mmol) in 160 mL of acetic acid was added dropwise. The reaction was then stirred at room temperature for 64 hrs. The resulting solids were isolated by filtration, washed with saturated [NAHCO3] solution and water, and dried to yield 60 g of material. The filtrate was evaporated to dryness, the residue was suspended in a saturated [NAHCO3] solution and additional product was extracted into ethyl acetate. The organic extracts were dried over sodium sulfate, filtered, and evaporated to yield an additional 6.2 g of product to give a total of 66 g of 2-aminobenzothiazole-6-sulfonic acid amide.

Reference： [1]Current Patent Assignee: ELI LILLY & CO - WO2004/11460, 2004, A2 Location in patent: Page 59-60

33
[ 98-62-4 ]
[ 74-89-5 ]
[ 1709-52-0 ]

Yield	Reaction Conditions	Operation in experiment
76%	With triethylamine; In ethanol; at 20 - 80℃; for 24h;	Method 23 4-(N-Methylsulphamoyl)aniline Methylamine (3ml of a 33% solution in ethanol) and then triethylamine (0.159ml, 1.1mmol) was added to sulphanilyl fluoride (200mg, 1.1mmol), and the mixture heated at 80C for 6 hours then at ambient temperature for 18 hours. The volatiles were removed by evaporation and the residue azeotroped with toluene to give the title compound (160mg, 76%). NMR: 2.30 (s, 3H), 5.85 (s, 2H), 6.60 (d, 2H), 7.39 (d, 2H); m/z: 187 [MH]+.
75%	In ethanol; at 20 - 80℃;	4-Aminobenzenesulphonylfluoride (200 mg, 1.14 mmol) was dissolved in a solution of methylamine in EtOH (3 mL, excess) and heated to 80 C. for 45 minutes, then cooled to room temperature and left to stir overnight. The solvent was evaporated in vacuo and azeotroped with ether to yield the title compound as a solid (160 mg, 75%). NMR: 2.12 (s, 31), 5.85 (s, 2H), 6.59 (d, 2H), 7.37 (d, 2H); miz 187.

Reference： [1]Patent: EP1214318,2003,B1 .Location in patent: Page/Page column 37
[2]Patent: US2004/14776,2004,A1 .Location in patent: Page/Page column 39

34
[ 888500-54-7 ]
[ 1709-52-0 ]
N-methyl-4-[4-(3-trifluoromethyl-pyrazol-1-yl)-quinolin-2-ylamino]-benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%	In butan-1-ol at 20 - 35℃; for 48h; Heating / reflux;	21 Example 21Synthesis of N-Methyl-4-[4-(3-trifluoromethyl-pyrazol-l-yl)-quinolin-2-ylamino]- benzenesulfonamide (E 21); E 214-(iV-Methylphenyl sulphonyl) aniline (205 mg, 1.11 mmol) was added to a stirred solution of 2-chloro-4-(3-trifluoromethyl-pyrazol-l-yl)-quinoline (300 mg, 1.01 mmol) in 1-butanol (10 mL), under nitrogen, at room temperature. This mixture was stirred under reflux for about 48 hrs and then filtered while hot. The resulting pale brown solid was stirred in /-PrOH, filtered off, and dried to give the desired product (225 mg, 50%). Melting range: 220-222 0C1H NMR (400 MHz, CDCl3) δ 9.25 (br s, D2O exchange, NH), 8.14-8.11 (m, 2H), 8.03 (d, J=I .6Hz, IH), 7.96 (d, J=8.1Hz, IH), 7.85-7.79 (m, 3H), 7.72-7.67 (m, IH), 7.42-7.29 (m, 2H), 6.86 (d, J=2.4Hz, IH), 5.73 (br s, D2Oexc, NH), 2.61 (d, J=5.1Hz, 3H).IR (Cm"1): 1605, 1505, 1480 MS (m/z): 448 (M+, 100%)

Reference： [1]Current Patent Assignee: DR REDDY&apos;S LABORATORIES LIMITED - WO2006/58201, 2006, A2 Location in patent: Page/Page column 141

35
[ 1709-52-0 ]
[ 223785-90-8 ]

Yield	Reaction Conditions	Operation in experiment
79%	In 4-isothiocyanato0benzamide	C.108 4-Isothiocyanato-N-methyl-benzenesulfonamide, which has the structural formula 4-Isothiocyanato-N-methyl-benzenesulfonamide, which has the structural formula was prepared in a manner analogous to 4-isothiocyanato-benzamide of Example C(102). 4-Amino-N-methyl-benzenesulfonamide (2.17 g, 11.7 mmol) gave 2.10 g (79% yield) of white fluffy powder, which was used without further purification. 1H NMR (DMSO-d6): δ 7.83 (2H, d, J=8.4 Hz), 7.65 (2H, d, J=8.4 Hz), 7.61 (1H, q, J=4.9 Hz), 2.43 (3H, d, J=4.9 Hz).

Reference： [1]Current Patent Assignee: PFIZER INC - US6569878, 2003, B1

36
[ 54-47-7 ]
[ 1709-52-0 ]
[ 608523-60-0 ]

Yield	Reaction Conditions	Operation in experiment
29%		20.B Step B. Step B. Preparation of 6-[4-(Methylsulfamoyl)phenylazo]-pyridoxal-5-phosphate The title material was prepared from 4-amino-N-methyl-benzenesulfonamide (step A) and pyridoxal-5-phosphate as described in general procedure D, method A. The final productproduct was obtained in 29% yield. 1H NMR (D2O): δ 2.30 (s, 3H), 2.83 (s, 3H), 5.51 (s, 2H), 7.76 (d, J=8.1, 2H), 7.86 (d, J=7.6, 2H), 10.26 (s, 1H). 31P NMR (D2O): δ 7.05 (s).

Reference： [1]Current Patent Assignee: TAIMED BIOLOGICS, INC. - US6638921, 2003, B1

37
[ 6319-45-5 ]
[ 7440-02-0 ]
[ 1709-52-0 ]

Yield	Reaction Conditions	Operation in experiment
	In methanol	76.6 Preparation of 4-[(N-methylamino)sulfonyl]aniline Step 6 Preparation of 4-[(N-methylamino)sulfonyl]aniline To a solution of N-methyl-4-nitrobenzenesulfonamide (Step 5) (4.8 g, 22.2 mmol) in methanol (100 ml) in a Parr bottle was added Raney-nickel in methanol. The reaction mixture was flushed with nitrogen and hydrogen several times and maintained under hydrogen at delivery pressure of 5 psi. After stirring at 25° C. for approximately 20 hr, the reaction was vented and purged with nitrogen. The contents of the reaction were filtered and concentrated to remove the solvent. The 4-[(N-methylamino)sulfonyl]aniline obtained as a white solid (4.1 g, 100%) was used in the next step without further purification: mp (DSC) 138° C. Anal Calc'd. for C7 H10 N2 O2 S 0.25 H2 O: C, 44.08; H, 5.55; N, 14.69. Found: C, 43.83; H, 5.39; N, 14.81.

Reference： [1]Current Patent Assignee: PFIZER INC - US5932598, 1999, A

38
[ 19602-82-5 ]
[ 1709-52-0 ]
2,2'-dithiobis-N-[4-[(methylamino)sulfonyl]phenyl]benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In pyridine; dichloromethane	2 2,2'-Dithiobis-N-[4-[(methylamino)sulfonyl]phenyl]benzamide EXAMPLE 2 2,2'-Dithiobis-N-[4-[(methylamino)sulfonyl]phenyl]benzamide This compound was prepared according to the general method of Example 1 using 2,2'-dithiobisbenzoyl chloride (2.2 g, 6.0 mmol) in 15 mL of dichloromethane and 4-[(methylamino)sulfonyl]aniline (3.0 g, 16.0 mmol) in 20 mL of pyridine. The crude product was recrystallized from dimethylformamide, ethanol, and 4% aqueous NaHCO3 to afford 1.9 g of the title compound, mp 245°-247° C.; NMR (DMSO-d6): δ10.9 (s, 2H), 7.9 (m, 4H), 7.7-7.8 (m, 8H), 7.5 (m, 2H), 7.3-7.4 (m, 6H), 2.4 (m, 6H).
	In pyridine; dichloromethane	2 2,2'-Dithiobis-N-[4-[(methylamino)sulfonyl]phenyl]benzamide EXAMPLE 2 2,2'-Dithiobis-N-[4-[(methylamino)sulfonyl]phenyl]benzamide This compound was prepared according to the general method of Example 1 using 2,2'-dithiobisbenzoyl chloride (2.2 g, 6.0 mmol) in 15 mL of dichloromethane and 4-[(methylamino)sulfonyl]aniline (3.0 g, 16.0 mmol) in 20 mL of pyridine. The crude product was recrystallized from dimethylformamide, ethanol, and 4% aqueous NaHCO3 to afford 1.9 g of the title compound, mp 245°-247° C.; NMR (DMSO-d6): δ10.9 (s, 2H), 7.9 (m, 4H), 7.7-7.8 (m, 8H), 7.5 (m, 2H), 7.3-7.4 (m, 6H), 2.4 (m, 6H).

Reference： [1]Current Patent Assignee: PFIZER INC - US5463122, 1995, A
[2]Current Patent Assignee: PFIZER INC - US5734081, 1998, A

39
[ 19602-82-5 ]
[ 109-02-4 ]
[ 1709-52-0 ]
2,2'-Dithiobis[N-[4-(aminosulfonyl)phenyl]methyl]benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran; dichloromethane	142 2,2'-Dithiobis[N-[4-(aminosulfonyl)phenyl]methyl]benzamide EXAMPLE 142 2,2'-Dithiobis[N-[4-(aminosulfonyl)phenyl]methyl]benzamide A solution of 1.86 g (10 mmol) of N-methyl sulfanilamide in 25 mL of tetrahydrofuran was treated with 1.01 g (10 mmol) of N-methyl-morpholine and cooled to 0° C. The resulting solution was treated rapidly, dropwise with a solution of 1.72 g (5.0 mmol) of 2,2'-dithiobisbenzoyl chloride in 25 mL of dichloromethane maintaining the temperature at 0° C. The reaction was stirred at 0° C. for 2 hours and then at room temperature for 18 hours. The solvent was removed in vacuo and the residue was partitioned between ethyl acetate/water. The organic layer was washed with 1.0M hydrochloric acid, water, dried (MgSO4), filtered and evaporated in vacuo. The residue was heated in dichloromethane for 4 hours and the solids were removed by filtration, washed with dichloromethane and dried in vacuo to give 1.94 g of the title compound, mp 243°-245° C.

Reference： [1]Current Patent Assignee: PFIZER INC - US5734081, 1998, A

40
[ 29509-91-9 ]
[ 1709-52-0 ]
[ 881194-19-0 ]

Yield	Reaction Conditions	Operation in experiment
43%	In butan-1-ol; for 72h;Heating / reflux;	To a solution of <strong>[29509-91-9]4-chloro-2,6-diphenyl-pyrimidine</strong> (0.2 g, 0.75 mmol) in n-BuOH (7 mL) was added 4-amino-N-methyl-benzenesulfonamide (0.146 g, 0.78 mmol) and the mixture was stirred at reflux temperature for 72 hours under nitrogen.The mixture was then cooled to temperature in the range of 20-400C, the solid precipitated was filtered off and dried to give the title compound (0.13 g, 43% yield)

Reference： [1]Patent: WO2006/34473,2006,A2 .Location in patent: Page/Page column 258

41
[ 1709-52-0 ]
[ 1774-47-6 ]
[ 1709-59-7 ]

Reference： [1]Synthetic Communications,2008,vol. 38,p. 3074 - 3081

42
[ 403792-70-1 ]
[ 420-04-2 ]
[ 1709-52-0 ]
[ 403792-64-3 ]

Yield	Reaction Conditions	Operation in experiment
20%	Stage #1: CYANAMID; N-methyl-4-aminobenzenesulfonamide With hydrogenchloride In methanol; diethyl ether; N,N-dimethyl acetamide at 100℃; for 0.5h; Stage #2: 5-(3-dimethylaminoprop-2-en-1-oyl)-1,2-dimethylimidazole With sodium methylate In methanol; diethyl ether; N,N-dimethyl acetamide at 180℃; for 1h;	160 Example 160; 4-(1,2-Dimethylimidazol-5-yl)-2-[4-(N-methylsulphamoyl)anilino]pyrimidine N-Methyl-4-aminobenzenesulphonamide (Method 110; 250 mg, 1.3 mmol) was dissolved in MeOH (3 ml) and 1M HCl in ether (1.3 ml, 1.3 mmol) added. Cyanamide (68 mg, 1.6 mmol) was added along with DMA (0.5 ml). The mixture was heated to 100° C. for 30 min. To this was added 5-(3-dimethylaminoprop-2-en-1-oyl)-1,2-dimethylimidazole (Method 15; 230 mg, 1.2 mmol) and sodium methoxide (150 mg, 2.6 mmol) and heated to 180° C. for 1 hr. The reaction mixture was poured into sat. sodium hydrogen carbonate solution and the resultant solid collected. The solid was triturated with hot DMF and filtered. The filtrate was evaporated in vacuo and purified by flash chromatography on silica gel eluding with DCM/2% methanolic ammonia (100:0 increasing in polarity to 85:15) to yield a white solid which was digested with acetonitrile to yield the title compound as a solid (84 mg, 20%). NMR: 2.38 (d, 6H), 3.95 (s, 3H), 7.19 (d, 2H), 7.63 (s, 1H), 7.68 (d, 2H), 7.93 (d, 2H), 8.43 (d, 1H), 9.91 (s, 1H); m/z 359.

Reference： [1]Current Patent Assignee: Breault, Gloria Anne; Newcombe, Nicholas John; Thomas, Andrew Peter - US2004/14776, 2004, A1 Location in patent: Page/Page column 30-31

43
[ 1709-52-0 ]
[ 3932-97-6 ]
[ 1141378-43-9 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 2,4-dichloro-5-trifluoromethylpyrimidine With zinc(II) chloride In diethyl ether; dichloromethane; <i>tert</i>-butyl alcohol at -5℃; for 1h; Stage #2: N-methyl-4-aminobenzenesulfonamide With triethylamine In diethyl ether; dichloromethane; <i>tert</i>-butyl alcohol at -5 - 40℃;

Reference： [1]Location in patent: scheme or table Walker, Daniel P.; Christopher Bi; Kalgutkar, Amit S.; Bauman, Jonathan N.; Zhao, Sabrina X.; Soglia, John R.; Aspnes, Gary E.; Kung, Daniel W.; Klug-McLeod, Jacquelyn; Zawistoski, Michael P.; McGlynn, Molly A.; Oliver, Robert; Dunn, Matthew; Li, Jian-Cheng; Richter, Daniel T.; Cooper, Beth A.; Kath, John C.; Hulford, Catherine A.; Autry, Christopher L.; Luzzio, Michael J.; Ung, Ethan J.; Roberts, W. Gregory; Bonnette, Peter C.; Buckbinder, Leonard; Mistry, Anil; Griffor, Matthew C.; Han, Seungil; Guzman-Perez, Angel [Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 23, p. 6071 - 6077]

44
[ 117-80-6 ]
[ 1709-52-0 ]
[ 1241891-95-1 ]

Yield	Reaction Conditions	Operation in experiment
61%	In ethanol; water at 120℃; for 72h;

Reference： [1]Location in patent: experimental part Lawrence, Harshani R.; Kazi, Aslamuzzaman; Luo, Yunting; Kendig, Robert; Ge, Yiyu; Jain, Sanjula; Daniel, Kenyon; Santiago, Daniel; Guida, Wayne C.; Sebti, Said M. [Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 15, p. 5576 - 5592]

45
[ 1709-52-0 ]
[ 54950-76-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: potassium carbonate / acetone / 11 h / 0 - 30 °C 2: thionyl chloride / methanol / 2 h / Reflux

Reference： [1]Wang, Gong-Bao; Wang, Lin-Fa; Li, Chao-Zhang; Sun, Jing; Zhou, Guang-Ming; Yang, Da-Cheng [Research on Chemical Intermediates, 2012, vol. 38, # 1, p. 77 - 89]

46
[ 1709-52-0 ]
[ 75-36-5 ]
[ 6884-87-3 ]

Yield	Reaction Conditions	Operation in experiment
72.4%	With potassium carbonate In acetone at 0 - 30℃; for 11h;

Reference： [1]Location in patent: experimental part Wang, Gong-Bao; Wang, Lin-Fa; Li, Chao-Zhang; Sun, Jing; Zhou, Guang-Ming; Yang, Da-Cheng [Research on Chemical Intermediates, 2012, vol. 38, # 1, p. 77 - 89]

47
[ 32315-10-9 ]
[ 1709-52-0 ]
[ 210907-84-9 ]
[ 1400220-87-2 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: bis(trichloromethyl) carbonate; N-methyl-4-aminobenzenesulfonamide With N-ethyl-N,N-diisopropylamine In dichloromethane Stage #2: 3-aminophenylboronic acid pinacolate With N-ethyl-N,N-diisopropylamine for 1h;	I.25 Synthesis of V-methyl-4- {3- [3-(4,4,5,5-tetramethyl- [ 1 ,3,2] dioxaborolan- 2-yl)-phenyl]-ureido}-benzenesulfonamide (intermediate 25)[00433] 4-Amino-N-methyl-benzenesulfonamide (0.4 g, 2.15 mmol) was dissolved in 20 mL dichloromethane and diisopropylethylamine (0.512 mL, 2.48 mmol), then solid triphosgene (237 mg, 0.86 mmol) was added. By LCMS (MeOH quench), <10% starting material remained so 3-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-phenylamine (471 mg, 2.15 mmol) and diisopropylethylamine (0.412 mL, 2.36 mmol) were added. The reaction was judged complete in 1 h by LCMS. MeOH (1 mL) was added and the reaction was stirred 18 h. The mixture was washed with DI water, saturated NaHC03, and 1 NHC1 and was dried over MgS04. After concentrtion in vacuo, an off-white solid was obtained. [M+H]+ m/z 433

Reference： [1]Current Patent Assignee: RUGA - WO2012/125981, 2012, A2 Location in patent: Page/Page column 135

48
[ 22118-09-8 ]
[ 1709-52-0 ]
[ 1339155-51-9 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate In tetrahydrofuran for 1h; Reflux;

Reference： [1]Dragovich, Peter S.; Fauber, Benjamin P.; Corson, Laura B.; Ding, Charles Z.; Eigenbrot, Charles; Ge, Hongxiu; Giannetti, Anthony M.; Hunsaker, Thomas; Labadie, Sharada; Liu, Yichin; Malek, Shiva; Pan, Borlan; Peterson, David; Pitts, Keith; Purkey, Hans E.; Sideris, Steve; Ultsch, Mark; Vanderporten, Erica; Wei, Binqing; Xu, Qing; Yen, Ivana; Yue, Qin; Zhang, Huihui; Zhang, Xuying [Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 11, p. 3186 - 3194]

49
[ 1709-52-0 ]
[ 76-05-1 ]
[ 651733-96-9 ]
[ 1470134-30-5 ]

Yield	Reaction Conditions	Operation in experiment
56%	In 2,2,2-trifluoroethanol at 20 - 80℃; for 24.2h;	5.1.7 4-(6-Amino-4-cyclohexylmethoxypyrimidin-2-ylamino)-amino-N-methylbenzenesulfonamide trifluoroacetate salt (12) To a solution of 10 (2.640g, 8mmol) and 11 (1.500g, 8mmol) in TFE (35mL), TFA (3.10mL, 40mmol) was added. The resulting mixture was stirred for 10min at r.t., then refluxed for 24h at 80°C. The precipitated solid was collected on a filter and washed with EtOAc to afford 12 as a white crystalline solid (1.500g). Solvents were removed in vacuo from the filtrate, water (30mL) was added, the pH was adjusted to neutral with saturated aqueous NaHCO3 and the mixture was extracted with EtOAc. The combined organic layers were washed with H2O, followed by brine, dried over MgSO4, and the solvent was removed in vacuo. The crude oil was purified by flash chromatography (CH2Cl2/MeOH 9.7/0.3) to obtain an additional crop of 12 as the free base (0.700g; overall yield 59%). M.p. 210-212°C (MeOH); 1H NMR (300MHz, DMSO-d6) δ 0.99-1.26 (m, 5H, C6H11), 1.69-1.77 (m, 6H, C6H11), 2.39 (s, 3H, CH3), 4.03 (d, J=6Hz, 2H, CH2O), 5.35 (s 1H, H5), 6.90 (vbr s, 2H, NH2, D2O exchangeable), 7.23 (br s, 2H, NH2, D2O exchangeable), 7.63 (d, J=8.7Hz, 2H, ArH), 7.93 (d, J=9.0Hz, 2H, ArH), 9.67 (s, 1H, NH, D2O exchangeable); 13C NMR (75MHz, DMSO-d6) δ 169.4, 163.9 br, 156.5 br, 143.8 br, 130.9 br, 127.5, 118.5 br, 78.4, 71.0, 36.7, 29.1, 28.6, 25.9, 25.1; MS (EI, 70eV) m/z 391 (M+), 361, 295 (100%). Anal. C18H25N5O3SCF3COOH (C, H, N).

Reference： [1]Boschi, Donatella; Tosco, Paolo; Chandra, Naveen; Chaurasia, Shilpi; Fruttero, Roberta; Griffin, Roger; Wang, Lan-Zhen; Gasco, Alberto [European Journal of Medicinal Chemistry, 2013, vol. 68, p. 333 - 338]

50
[ 1709-52-0 ]
[ 1470134-32-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 2,2,2-trifluoroethanol / 24.2 h / 20 - 80 °C 2: sodium nitrite; acetic acid / water / 1 h / 95 °C

Reference： [1]Boschi, Donatella; Tosco, Paolo; Chandra, Naveen; Chaurasia, Shilpi; Fruttero, Roberta; Griffin, Roger; Wang, Lan-Zhen; Gasco, Alberto [European Journal of Medicinal Chemistry, 2013, vol. 68, p. 333 - 338]

51
[ 1709-52-0 ]
[ 1470134-33-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 2,2,2-trifluoroethanol / 24.2 h / 20 - 80 °C 2: sodium nitrite; acetic acid / water / 1 h / 95 °C 3: [bis(acetoxy)iodo]benzene / acetonitrile / 2 h / 20 °C

Reference： [1]Boschi, Donatella; Tosco, Paolo; Chandra, Naveen; Chaurasia, Shilpi; Fruttero, Roberta; Griffin, Roger; Wang, Lan-Zhen; Gasco, Alberto [European Journal of Medicinal Chemistry, 2013, vol. 68, p. 333 - 338]

52
(2R,3R)-3-[(5-bromo-2-chloropyrimidin-4-yl)amino]butan-2-ol [ No CAS ]
[ 1709-52-0 ]
4-[(5-bromo-4-[(2R,3R)-3-hydroxybutan-2-yl]amino}pyrimidin-2-yl)amino]-N-methylbenzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride In 1,4-dioxane; water; acetonitrile for 17h; Reflux;

Reference： [1]Luecking, Ulrich; Jautelat, Rolf; Krueger, Martin; Brumby, Thomas; Lienau, Philip; Schaefer, Martina; Briem, Hans; Schulze, Julia; Hillisch, Alexander; Reichel, Andreas; Wengner, Antje Margret; Siemeister, Gerhard [ChemMedChem, 2013, vol. 8, # 7, p. 1067 - 1085]

53
[ 27631-29-4 ]
[ 1709-52-0 ]
4-((2-chloro-6,7-dimethoxyquinazolin-4-yl)amino)-N-methylbenzene sulfonamide hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	In ethanol for 24h; Reflux;	4.1.15 General procedure for S_NAr General procedure: A mixture of 0.80mmol aryl chloride and 0.80mmol aniline in 20mL ethanol or isopropyl alcohol was stirred at reflux for 24h. The resulting precipitate was filtered while hot and purified as described below.

Reference： [1]Barbosa, Maria Letícia De Castro; Lima, Lídia Moreira; Tesch, Roberta; Sant'Anna, Carlos Mauricio R.; Totzke, Frank; Kubbutat, Michael H.G.; Schächtele, Christoph; Laufer, Stefan A.; Barreiro, Eliezer J. [European Journal of Medicinal Chemistry, 2014, vol. 71, p. 1 - 14]

54
[ 62-53-3 ]
[ 1709-52-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: acetic acid; sodium acetate / 0.5 h / 20 °C 2: 0.5 h / 60 °C 3: dichloromethane; tetrahydrofuran / 0.5 h / 20 °C 4: potassium hydroxide; water / methanol / 24 h / 65 °C

Reference： [1]Barbosa, Maria Letícia De Castro; Lima, Lídia Moreira; Tesch, Roberta; Sant'Anna, Carlos Mauricio R.; Totzke, Frank; Kubbutat, Michael H.G.; Schächtele, Christoph; Laufer, Stefan A.; Barreiro, Eliezer J. [European Journal of Medicinal Chemistry, 2014, vol. 71, p. 1 - 14]

55
[ 103-84-4 ]
[ 1709-52-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 0.5 h / 60 °C 2: dichloromethane; tetrahydrofuran / 0.5 h / 20 °C 3: potassium hydroxide; water / methanol / 24 h / 65 °C

Reference： [1]Barbosa, Maria Letícia De Castro; Lima, Lídia Moreira; Tesch, Roberta; Sant'Anna, Carlos Mauricio R.; Totzke, Frank; Kubbutat, Michael H.G.; Schächtele, Christoph; Laufer, Stefan A.; Barreiro, Eliezer J. [European Journal of Medicinal Chemistry, 2014, vol. 71, p. 1 - 14]

56
[ 1709-52-0 ]
[ 1533434-81-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: calcium carbonate / dichloromethane; water / 0 - 20 °C / 760.05 Torr / Inert atmosphere 2.1: sodium methylate / 0.25 h / 20 °C / 760.05 Torr / Inert atmosphere 2.2: 1 h / 760.05 Torr / Inert atmosphere 2.3: 20 °C / 760.05 Torr / Inert atmosphere

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - WO2014/6066, 2014, A1

57
[ 1709-52-0 ]
[ 443799-42-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: calcium carbonate / dichloromethane; water / 0 - 20 °C / 760.05 Torr / Inert atmosphere 2.1: sodium methylate / 0.25 h / 20 °C / 760.05 Torr / Inert atmosphere 2.2: 1 h / 760.05 Torr / Inert atmosphere 2.3: 20 °C / 760.05 Torr / Inert atmosphere 3.1: hydrazine / ethanol / 3 h / 65 °C / 760.05 Torr / Inert atmosphere

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - WO2014/6066, 2014, A1

58
[ 1709-52-0 ]
[ 19026-84-7 ]
2-[4-(N,N-dimethylsulfamoyl)phenylamino]-N-adamantylbenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%	With Cp*Ir(OCOCH₃)₂; copper diacetate; silver(I) triflimide In 1,2-dichloro-ethane at 25℃; for 24h; Inert atmosphere;

Reference： [1]Kim, Hyunwoo; Shin, Kwangmin; Chang, Sukbok [Journal of the American Chemical Society, 2014, vol. 136, # 16, p. 5904 - 5907]

59
[ 1709-52-0 ]
[ 4635-59-0 ]
C₁₁H₁₅ClN₂O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With disodium hydrogenphosphate In chloroform at 0 - 20℃;	To a solution of 4-amino-N-methylbenzenesulfonamide (200 mg, 1.1 mmol) and Na2HPO4 (300 mg, 2.2 mmol) in CHCl3 (10 mL) was added 4-chlorobutanoyl chloride (151 mg, 1.1 mol) drop-wise at 0° C. After reagent addition, the mixture was allowed to stir at room temperature. The mixture was concentrated to give crude sm-15, which was used directly in the next step without further purification.

Reference： [1]Current Patent Assignee: SCRIPPS RESEARCH - US2014/271955, 2014, A1 Location in patent: Paragraph 0784

60
[ 85-44-9 ]
[ 1709-52-0 ]
N,N-phthaloyl-sulfanilic acid methylamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In acetic acid at 130℃; for 3h;	To a solution of 27-3 (0.5 g, 2.68 mmol) in AcOH (40 mL) was added 27-4 (0.433 g, 2.92 mmol). The reaction mixture was stirred at 130° C. for 3 h. The reaction mixture was cooled down, and the solvent was removed to afford crude product which was used directly in the next step.

Reference： [1]Current Patent Assignee: SCRIPPS RESEARCH - US2014/271955, 2014, A1 Location in patent: Paragraph 0751

61
[ 1709-52-0 ]
C₁₁H₁₄N₂O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: disodium hydrogenphosphate / chloroform / 0 - 20 °C 2: sodium ethanolate / ethanol / 3 h / 0 °C

Reference： [1]Current Patent Assignee: SCRIPPS RESEARCH - US2014/271955, 2014, A1

62
[ 1709-52-0 ]
C₁₅H₁₄N₂O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: acetic acid / 3 h / 130 °C 2: zinc / acetic acid / 3 h / 130 °C

Reference： [1]Current Patent Assignee: SCRIPPS RESEARCH - US2014/271955, 2014, A1

63
[ 1709-52-0 ]
2-chloro-4-(4-(2-nitrophenoxy)phenyl)pyrimidine [ No CAS ]
N-methyl-4-((4-(4-(2-nitrophenoxy)phenyl)pyrimidin-2-yl)amino)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
42%	With hydrogenchloride In ethanol; water at 160℃; for 2h; Microwave irradiation;	17 4.8 Preparation of Compounds General procedure: General Procedure I: A reaction mixture of 2-Chloro-4-[4-(2-nitrophenoxy)phenyl]pyrimidine (150mg, 0.46mmol), Aniline (42μg, 0.46mmol) and catalytic amount of 1N HCl (a few drops) in Ethanol (5mL) was heated for 2h at 160°C under microwave irradiation. After cooling and evaporation of the mixture, the resulting solid was washed with methanol (20mL) to give 4-[4-(2-Nitrophenoxy)phenyl]-N-phenyl-pyrimidin-2-amine (7a) (89mg, 51% yield) as an intermediate. To a solution of 7a (60mg, 0.16mmol) in EtOH (6mL) were added Fe (57mg, 1.02mmol) and NH4Cl (7mg, 0.13mmol) in H2O (2mL). The mixture was stirred vigorously for 30min at 85°C and monitored by TLC. After cooling to room temperature, the mixture was diluted with EtOAc (50mL), and washed with brine (30mL x 2). The combined organic phases were dried over anhydrous MgSO4, filtered and concentrated in vacuo. After removal of the solvent, the residue was purified by flash chromatography (ethylacetate/hexanes) on silica gel to give the desired product 3a (41mg, 74% yield).4.8.17 N-Methyl-4-{{4-[4-(2-nitrophenoxy)phenyl]pyrimidin-2-yl}amino}benzenesulfonamide (3r) Compound 3r was prepared (92 mg, 42% yield) according to GP I from 4-Amino-N-methyl-benzenesulfonamide instead of Aniline as a starting material without final reduction of the nitro group. mp 148-152 °C. 1H NMR (500 MHz, DMSO-d6) δ 10.17 (s, 1H), 8.61 (d, J = 5.0 Hz, 1H), 8.25 (d, J = 8.6 Hz, 2H), 8.12 (d, J = 7.0 Hz, 1H), 8.06 (d, J = 8.6 Hz, 2H), 7.78-7.72 (m, 3H), 7.50-7.44 (m, 2H), 7.34 (d, J = 8.0 Hz, 1H), 7.24-7.20 (m, 3H), 2.40 (d, J = 4.9 Hz, 3H). 13C NMR (100 MHz, DMSO-d6) δ 162.9, 159.7, 159.1, 158.6, 148.1, 144.3, 141.7, 135.3, 132.1, 130.8, 129.2, 127.8, 125.8, 125.3, 122.4, 118.1, 118.0, 108.7, 28.7. HRMS (ESI+) m/z calcd for C23H19N5NaO5S [M + Na]+, 500.0999; found, 500.1026.
92 mg	With hydrogenchloride In ethanol at 160℃; for 2h; Microwave irradiation;

Reference： [1]Shin, Yongje; Lim, Sang Min; Yan, Hong Hua; Jung, Sungwoo; Fang, Zhenghuan; Jung, Kyung Hee; Hong, Soon-Sun; Hong, Sungwoo [European Journal of Medicinal Chemistry, 2016, vol. 123, p. 544 - 556]
[2]Park, Hwangseo; Shin, Yongje; Choe, Hyeonjeong; Hong, Sungwoo [Journal of the American Chemical Society, 2015, vol. 137, # 1, p. 337 - 348]

64
[ 1709-52-0 ]
[ 154807-47-3 ]
5-amino-3-methyl-N-[4-(methylsulfamoyl)phenyl]-1,2-thiazole-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
333 mg	With triethylamine In tetrahydrofuran at 20℃; for 48h;	5-Amino-3-methy[-N-[4-(methy[su[famoy[)pheny[]-1 ,2-thiazo[e-4-carboxamide A mixture of 5-amino-3-methy[-1 ,2-thiazo[e-4-carboxy[ic acid [CAS-RN: 22131-51-7, for the synthesis, please see: J. Goerdeler, H. Horn, Chem. Ber. (1963), 96, 1551- 1560.] (1.8 g, 11.4 mmol, 1.0 eq) and thionyl chloride (9.1 mL, 125 mmol, 11.0 eq) was stirred at 80 °C for 5 h. After cooling, the volatile components were removedin vacuo. The crude acid chloride was diluted with toluene and concentrated at the rotary evaporator. This process was repeated one more time to give 2.4 g of the crude acid chloride. 4-amino-N-methylbenzenesulfonamide [CAS-RN: 1709-52-0] (0.7 g, 3.7 mmol, 1.0 eq) and triethyl amine (15.8 mL, 113 mmol, 3.0 eq) were dissolved in 31 mL THF, then 0.8 g (3.7 mmol, 1.0 eq) acid chloride dissolved inTHF (32 mL) was added. The reaction mixture was stirred at rt for 48 hours. After removal of the volatile components by the purification of this crude material was achieved via preparative MPLC (Biotage Isolera; SNAP cartridge: dicloromethane -> dichloromethane/ethanol 80:20) to give 333 mg (27% yield of theory) of the title compound.UPLC-MS (Method 2): Rt = 0.74 mm; MS (EI0): m/z = 327 [M+H]

Reference： [1]Current Patent Assignee: BAYER AG - WO2015/113920, 2015, A1 Location in patent: Page/Page column 152

65
[ 67-56-1 ]
[ 63-74-1 ]
[ 1709-52-0 ]

Yield	Reaction Conditions	Operation in experiment
98%	With bis[dichloro(pentamethylcyclopentadienyl)ruthenium(III)]; bis[2-(diphenylphosphino)phenyl] ether; lithium tert-butoxide at 40℃; for 24h;

Reference： [1]Dang, Tuan Thanh; Ramalingam, Balamurugan; Seayad, Abdul Majeed [ACS Catalysis, 2015, vol. 5, # 7, p. 4082 - 4088]

66
[ 67-56-1 ]
[ 63-74-1 ]
[ 1709-52-0 ]
[ 137473-37-1 ]

Yield	Reaction Conditions	Operation in experiment
1: 60% 2: 40%	With bis[dichloro(pentamethylcyclopentadienyl)ruthenium(III)]; bis[2-(diphenylphosphino)phenyl] ether; lithium tert-butoxide at 60℃; for 24h;

Reference： [1]Dang, Tuan Thanh; Ramalingam, Balamurugan; Seayad, Abdul Majeed [ACS Catalysis, 2015, vol. 5, # 7, p. 4082 - 4088]

67
[ 100397-13-5 ]
[ 1709-52-0 ]
C₂₀H₂₀N₂O₄S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With acetic acid In ethanol at 125℃; for 3h; Microwave irradiation;

Reference： [1]Credille, Cy V.; Chen, Yao; Cohen, Seth M. [Journal of Medicinal Chemistry, 2016, vol. 59, # 13, p. 6444 - 6454]

68
[ 1709-52-0 ]
[ 109-77-3 ]
[4-(N-methylsulfamoyl)phenyl]carbonhydrazonoyl dicyanide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	Stage #1: N-methyl-4-aminobenzenesulfonamide With hydrogenchloride; sodium nitrite In water Cooling with ice; Stage #2: malononitrile With sodium acetate In ethanol; water for 2h; Cooling with ice;	General procedure for the synthesis of [4-(N-substitutedsulfamoyl)phenyl]carbon-hydrazonoyl dicyanides 3a-c General procedure: A solution of sodium nitrite (0.9 g, 0.013 mol) in distilled water (5 mL) was added portionwise to an ice cold solution of sulfanilamide derivatives namely: N-methylsulfanilamide, N-butylsulfanilamide and/or N-cyclohexylsulfanilamide 1a-c (0.01 mol) in concentrated hydrochloric acid (2.5 mL) and distilled water (5 mL). This solution was added portionwise to a well-stirred cold solution of malononitrile (0.66 g, 0.01 mol) in ethanol (30 mL) containing sodium acetate (0.9 g, 0.011 mol). The reaction mixture was kept in an ice bath for 2 h and the formed precipitate was filtered, washed several times with water, dried and recrystallized from ethanol to give title compounds 3a-c, respectively.

Reference： [1]Abbas, Hebat-Allah S.; Abd El-Karim, Somaia S.; Ahmed, Entesar M.; Eweas, Ahmad F.; El-Awdan, Sally A. [Acta poloniae pharmaceutica, 2016, vol. 73, # 5, p. 1163 - 1180]

69
[ 1709-52-0 ]
[ 101137-69-3 ]
N-(4-(N-methylsulfamoyl)phenyl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With [(1,3-bis-(2,6-diisopropylphenyl)-1,3-dihydro-2H-imidazol-2-ylidene)PdCl(μ-Cl)]₂; potassium carbonate In 1,2-dimethoxyethane at 110℃; for 15h;
74%	With [Pd(IPr)(acac)Cl]; potassium carbonate In 1,2-dimethoxyethane at 110℃; for 16h; Schlenk technique; Inert atmosphere;

Reference： [1]Li, Guangchen; Zhou, Tongliang; Poater, Albert; Cavallo, Luigi; Nolan, Steven P.; Szostak, Michal [Catalysis science and technology, 2020, vol. 10, # 3, p. 710 - 716]
[2]Zhou, Tongliang; Li, Guangchen; Nolan, Steven P.; Szostak, Michal [Organic Letters, 2019, vol. 21, # 9, p. 3304 - 3309]

70
[ 1709-52-0 ]
2-(6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl)-2-azaspiro[3.4]octan-6-one [ No CAS ]
C₂₂H₂₄F₃N₅O₂S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
29.9%	With methanol; sodium cyanoborohydride; acetic acid at 45℃; for 8h;	B.B176 Preparation of Compound 279 2-(6-(2,2,2-trifluoroethyDthieno[2,3-d]pyrimidin-4-yl)-2-azaspiro[3.4]octan-6-one intermediate 4 (244 mg, 0.72 mmol), 4-amino-N-methylbenzenesulfonamide (200 mg, 1.07 mmol), sodium cyanoborohydride (90 mg, 1.43 mmol) and dry methanol (9.5 mL) were added to a 40 mL glass bottle, and then acetic acid (86.0 mg, 1.43 mmol) in dry methanol (0.5 mL) was added. The resulting mixture was stirred at 45 °C for 8 h. The mixture was concentrated under reduced pressure to give a residue, which was dissolved in DCM(30 mL) before washed with water (20 mL x 3). The organic extracts were dried over anhydrous Na2SOu,filtered and concentrated to dryness under reduced pressure to give a residue, which was purified by prep-HPLC (Column: Xbridge 15030mm10um, Mobile Phase A: water (0.05% ammonia hydroxide v/v)-ACN, Mobile Phase B: acetonitrile, Flow rate: 25 mL/min, gradient condition from 35%B to 65%). The pure fractions were collected and the solvent was evaporated under vacuum. The residue was partitioned between CH3CN (2 mL) and water (10 mL). The mixture was lyophilized to dryness to give Compound 279 (racemate) (115.0 mg, 29.9% yield) as a white powder.

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2019/120209, 2019, A1 Location in patent: Page/Page column 354

71
[ 1709-52-0 ]
2-(6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl)-2-azaspiro[3.4]octan-6-one [ No CAS ]
C₂₂H₂₄F₃N₅O₂S₂ [ No CAS ]
C₂₂H₂₄F₃N₅O₂S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With methanol; sodium cyanoborohydride; acetic acid at 45℃; for 8h;	B.B176 Preparation of Compound 279 General procedure: 2-(6-(2,2,2-trifluoroethyDthieno[2,3-d]pyrimidin-4-yl)-2-azaspiro[3.4]octan-6-one intermediate 4 (244 mg, 0.72 mmol), 4-amino-N-methylbenzenesulfonamide (200 mg, 1.07 mmol), sodium cyanoborohydride (90 mg, 1.43 mmol) and dry methanol (9.5 mL) were added to a 40 mL glass bottle, and then acetic acid (86.0 mg, 1.43 mmol) in dry methanol (0.5 mL) was added. The resulting mixture was stirred at 45 °C for 8 h. The mixture was concentrated under reduced pressure to give a residue, which was dissolved in DCM(30 mL) before washed with water (20 mL x 3). The organic extracts were dried over anhydrous Na2SOu,filtered and concentrated to dryness under reduced pressure to give a residue, which was purified by prep-HPLC (Column: Xbridge 15030mm10um, Mobile Phase A: water (0.05% ammonia hydroxide v/v)-ACN, Mobile Phase B: acetonitrile, Flow rate: 25 mL/min, gradient condition from 35%B to 65%). The pure fractions were collected and the solvent was evaporated under vacuum. The residue was partitioned between CH3CN (2 mL) and water (10 mL). The mixture was lyophilized to dryness to give Compound 279 (racemate) (115.0 mg, 29.9% yield) as a white powder. The following Compounds were prepared starting from intermediate 4 and the corresponding amine, by using an analogous reductive amination method as was used for preparation of compound 276, Compound 277 or Compound 279 as indicated in the table below; one ofthe following 4 solvents were used: DCM, DCE, MeOH, MeCN.

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2019/120209, 2019, A1 Location in patent: Page/Page column 354; 358

72
[ 1709-52-0 ]
2-[4-[(cyclopentyloxy)methyl]-2,6-bis(propan-2-yl)phenyl]-N-[2-(hydroxymethyl)-4-(methylsulfamoyl)benzenesulfonyl]acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: N-Bromosuccinimide / N,N-dimethyl-formamide / 20 °C 2.1: palladium diacetate; 1,1'-bis-(diphenylphosphino)ferrocene; triethylamine / 110 °C / Inert atmosphere 3.1: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / 0 °C / Inert atmosphere 4.1: hydrogenchloride; sodium nitrite / water / 0.33 h / 10 °C 4.2: 0.5 h / -10 °C 5.1: ammonia / tetrahydrofuran / 0 - 20 °C 6.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere 6.2: 4 h / 20 °C