[ CAS No. 424792-57-4 ] {[proInfo.proName]}

Name: 424792-57-4|1,2-Difluoro-4-(methylsulfonyl)benzene|95%
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Quality Control of [ 424792-57-4 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 424792-57-4 ]

Product Details of [ 424792-57-4 ]

CAS No. :	424792-57-4	MDL No. :	MFCD04037934
Formula :	C₇H₆F₂O₂S	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	-
M.W :	192.18	Pubchem ID :	-
Synonyms :

Calculated chemistry of [ 424792-57-4 ]

Physicochemical Properties

Num. heavy atoms :	12
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.14
Num. rotatable bonds :	1
Num. H-bond acceptors :	4.0
Num. H-bond donors :	0.0
Molar Refractivity :	39.45
TPSA :	42.52 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.29 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.39
Log Po/w (XLOGP3) :	1.66
Log Po/w (WLOGP) :	3.29
Log Po/w (MLOGP) :	2.38
Log Po/w (SILICOS-IT) :	1.98
Consensus Log Po/w :	2.14

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-2.38
Solubility :	0.799 mg/ml ; 0.00416 mol/l
Class :	Soluble
Log S (Ali) :	-2.17
Solubility :	1.31 mg/ml ; 0.00681 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.27
Solubility :	0.103 mg/ml ; 0.000536 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.98

Safety of [ 424792-57-4 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 424792-57-4 ]

* 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.

Upstream synthesis route of [ 424792-57-4 ]
Downstream synthetic route of [ 424792-57-4 ]

[ 424792-57-4 ] Synthesis Path-Upstream 1~3

1
[ 130922-41-7 ]
[ 424792-57-4 ]

Reference： [1] Patent: WO2007/31747, 2007, A1, . Location in patent: Page/Page column 59-60
[2] Patent: WO2008/74966, 2008, A1, . Location in patent: Page/Page column 13-14

2
[ 75-75-2 ]
[ 367-11-3 ]
[ 424792-57-4 ]

Yield	Reaction Conditions	Operation in experiment
59%	Stage #1: Reflux Stage #2: at 80 - 120℃;	Step 1: 1,2-Difluoro-4-methanesulfonyl-benzene; A mixture of thionyl chloride (12.73 mL, 0.175 mol) and methanesulfonic acid (28.4 mL, 0.438 mol) was heated at reflux overnight and then cooled to 80° C. 1,2-Difluorobenzene (8.64 mL, 88 mmol) was and trifluoromethanesulfonic acid (0.675 mL, 8.8 mmol) were added dropwise. The reaction mixture was then heated at 120° C. for 3 h, cooled to room temperature and poured into ice-water (200 mL). The mixture was extracted three times with ethyl acetate and the combined organic extracts were dried (sodium sulfate), filtered, evaporated, and purified by flash chromatography, eluting with 15percent ethyl acetate/hexanes, to give 1,2-difluoro-4-methanesulfonyl-benzene (9.98 g, 59percent) as a white solid. ¹H NMR (300 MHz, CDCl₃) δ 3.27 (s, 3H), 7.70-7.84 (m, 2H), 8.02-8.09 (m, 1H).
46%	Stage #1: at 90℃; Heating / reflux Stage #2: at 80 - 120℃; for 3 - 6 h;	EXAMPLE 1; Preparation of r2-Fluoro-4-(methylsulfonvπphenyl]hvdrazine (2008180); 2008101 <n="10"/>1. Preparation of 1 ,2-Difluoro-4-(methylsulfonγDbenzene (2008101)2008101A mixture of methanesulfonic acid (22.18 kg, 230.78 mol) and thionyl chloride (11.00 kg, 89.66 mol) was carefully heated to 9O⁰C over 10 h (a scrubber containing dilute sodium hydroxide solution was used to prevent emission of corrosive gases) and then maintained at 9O⁰C overnight. The resultant solution was then heated to 12O⁰C and a solution of 1,2- difluorobenzene (5.263 kg, 46.17 mol) and trifluoroniethanesulfonic acid (0.71 kg, 4.71 mol) was added dropwise over 2 h at 115-12O⁰C. Upon complete addition the reaction mixture was heated at 12O⁰C for a further 4 h, cooled to 50⁰C, and divided into 2 equal portions. Each portion was carefully added to water (50 kg) at 5O⁰C, causing the temperature of the mixture to rise to ca.70 ⁰C. The mixture was then cooled to 35°C and the product was extracted with dichloromethane (9.47 kg). The combined organic fractions derived from the two portions were separated, dried, and concentrated to a thick slush. Hexane (3.19 kg) was added and the resultant precipitate was collected by filtration, washed with hexane (1.6 kg), and dried in air to give l,2-difluoro-4- (methylsulfonyl)benzene (2008101) (4.23 kg, 48 percent) as a white solid, m.p. 1 A-ITQ.; EXAMPLE 2; Preparation of 2-Fluoro-(4-methylsulfonyl)phenol 2020463; 2008101; 1. Preparation of l,2-Difluoro-4-(methylsulfonvDbenzene 2008101; Carried out over two equal batches. Thionyl chloride (2.92 kg, 24.6 mol) and methanesulfonic acid (5.90 kg, 61.4 mol) were heated at reflux overnight in the presence of a scrubber. The reaction mixture was then cooled to 80°C, 1,2-difluorobenzene (1.40 kg, 12.3 mol) and trifluomethanesulfonic acid (110 mL, 1.22 mol) were added, and the resultant reaction mixture was heated at 12O⁰C for 3 h before being allowed to cool to room temperature. The reaction was then poured onto a mixture of ice/water (40 L), the resultant precipitate was collected by filtration, washed with water, and recrystallised <n="12"/>from isopropyl alcohol (2.5 L) to give l,2-difluoro-4-(methylsulfonyl)benzene 2008101 (1.08 kg, 46percent) as a white solid, mp 72-74°C.

Reference： [1] Patent: US2009/286812, 2009, A1, . Location in patent: Page/Page column 18
[2] Patent: WO2007/54668, 2007, A1, . Location in patent: Page/Page column 8-9; 10-11

3
[ 367-11-3 ]
[ 124-63-0 ]
[ 424792-57-4 ]

Reference： [1] Patent: US2004/220194, 2004, A1, . Location in patent: Page 23

[ 424792-57-4 ] Synthesis Path-Downstream 1~57

1
[ 367-11-3 ]
[ 124-63-0 ]
[ 424792-57-4 ]

Yield	Reaction Conditions	Operation in experiment
	With aluminum (III) chloride; at 90℃; for 18h;	Step 1: To AlCl3 (4.43 g, 33 mmol) in 1,2-difluorobenzene (10.0 ml, 101 mmol) add CH3SO2Cl (4.00 g, 2.7 mmol). Heat at 90 C. 18 h, allow to cool, and quench with ice-water. Extract with ether, dry (MgSO4) and concentrate to obtain the sulfone as a yellow solid

Reference： [1]Patent: US2004/220194,2004,A1 .Location in patent: Page 23

2
[ 110-85-0 ]
[ 424792-57-4 ]
1-(2-fluoro-4-methanesulfonyl-phenyl)-piperazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 90℃; for 5h;	Step 2: Combine the product of Step 1 (2.32 g, 12.1 mmol), piperazine (6.24 g, 72 mmol), and K2CO3 (3.34 g, 24 mmol) in DMF (20 ml). Heat at 90 C. 5 h, allow to cool, and concentrate. Partition between CH2Cl2 and water, wash with brine, dry (MgSO4) and concentrate to obtain the title compound as a yellow solid

Reference： [1]Patent: US2004/220194,2004,A1 .Location in patent: Page 23

4
[ 424792-57-4 ]
[ 929212-99-7 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogensulfide; In 1-methyl-pyrrolidin-2-one; at 20 - 80℃;	A mixture of 1 ,2-difluoro-4-methanesulfonylbenzene (2.8 g), sodium hydrogensulfide (11 g) and 1-methylpyrrolidin-2-one (30 ml_) was stirred at 80 0C for 90 minutes and then at room temperature overnight. The mixture was diluted with water (40 ml_), acidified by the addition of concentrated hydrochloric acid and then extracted with ethyl acetate. The combined extracts were dried over magnesium sulfate and the solvent removed under reduced pressure. The residue was crystallised from toluene to afford title compound as cream crystals, 1.4 g.MS: ESI (+ve) (Method B): 411 (M+H)+, Retention time 3.1 min.
	With 1-methyl-pyrrolidin-2-one; sodium hydrogensulfide; at 20 - 80℃;	Preparation 2b: bis(2-fluoro-4-methanesulfonylbenzene)disulfideA mixture of 1 ,2-difluoro-4-methanesulfonylbenzene (2.8 g), sodium hydrogensulfide (11 g) and 1-methylpyrrolidin-2-one (30 ml_) was stirred at 80 0C for 90 minutes and then at room temperature overnight. The mixture was diluted with water (40 ml_), acidified by the addition of concentrated hydrochloric acid and then extracted with ethyl acetate. The combined extracts were dried over magnesium sulfate and the solvent removed under reduced pressure. The residue was crystallised from toluene to afford title compound as cream crystals, 1.4 g.MS: ESI (+ve) (Method B): 411 (M+H)+, Retention time 3.1 min.

Reference： [1]Patent: WO2007/31747,2007,A1 .Location in patent: Page/Page column 60
[2]Patent: WO2008/74966,2008,A1 .Location in patent: Page/Page column 14

5
[ 130922-41-7 ]
[ 424792-57-4 ]

Yield	Reaction Conditions	Operation in experiment
	With 3-chloro-benzenecarboperoxoic acid; In dichloromethane; at 20℃;	3-Chloroperoxybenzoic acid (19 g) was added portionwise to a solution of 1 ,2- difluoro-4-methylsulfanylbenzene (5.4 g) in dichloromethane (100 mL) at room temperature and the resulting mixture was stirred at room temperature overnight. The mixture was washed with saturated aqueous sodium thiosulfate solution and EPO <DP n="61"/>saturated aqueous sodium hydrogen carbonate solution and then dried over magnesium sulfate. The solvent was removed under reduced pressure to afford title compound as a white solid, 5.5 g.1H NMR (CDCI3): delta 3.05 (s, 3H), 7.40 (m, 1 H), 7.75-7.85 (m, 2H).
	With 3-chloro-benzenecarboperoxoic acid; In dichloromethane; at 20℃;	Example 2: [6-fluoro-3-(2-fluoro-4-methanesulfonylphenylsulfanyl)-2- methylindolizin-1-yl]acetic acid30 Preparation 2a: 1 ,2-difluoro-4-methanesulfonylbenzene <n="15"/>3-Chloroperoxybenzoic acid (19 g) was added portionwise to a solution of 1 ,2- difluoro-4-methylsulfanylbenzene (5.4 g) in dichloromethane (100 mi_) at room temperature and the resulting mixture was stirred at room temperature overnight. The mixture was washed with saturated aqueous sodium thiosulfate solution and saturated aqueous sodium hydrogen carbonate solution and then dried over magnesium sulfate. The solvent was removed under reduced pressure to afford title compound as a white solid, 5.5 g.1H NMR (CDCI3): delta 3.05 (s, 3H), 7.40 (m, 1H), 7.75-7.85 (m, 2H).

Reference： [1]Patent: WO2007/31747,2007,A1 .Location in patent: Page/Page column 59-60
[2]Patent: WO2008/74966,2008,A1 .Location in patent: Page/Page column 13-14

6
[ 424792-57-4 ]
(2-fluoro-4-(methylsulfonyl)phenyl)hydrazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With hydrazine; In isopropyl methanesulfonate; at 0℃;Heating / reflux;	2. Preparation of r2-Fluoro-4-(methylsulfonvnphenyllhvdrazine (2008180); 2008180 <n="11"/>A solution of hydrazine hydrate (13.26 kg, 26.52 mol) in IMS (27.93 kg) was heated at reflux and l,2-difluoro-4-(methylsulfonyl)benzene (2008101) (4.42 kg, 23.00 mol) was carefully added portionwise over 3 h. The solution was then heated under reflux overnight and allowed to cool to 0C over 24 h. The resultant product was collected by filtration, washed with IMS (3.5 kg), and dried in air to give [2-fluoro-4- (methylsulfonyl)phenyl]hydrazine (2008180) (3.62 kg, 86 %) as a white solid, m.p. 135.5-138.5C. Rf 0.17 (1:1 toluene/ethyl acetate).
70%	With hydrazine hydrate; In ethanol;Reflux;	A solution of hydrazine hydrate (195.36 mg, 3.903 mmol) and l,2-difluoro-4-(methylsulfonyl)benzene 9b (500 mg, 2.602 mmol) in ethanol (10 mL) was heated under reflux overnight and allowed to cool to 20 C. The resultant product was collected by filtration, washed with ethanol and dried to give (2-fluoro-4-(methylsulfonyl)phenyl)hydrazine 10b (440 mg, 70 %) as a white solid. 1H NMR (DMSO-d6) delta 7.69 (s, 1H), 7.51 (dd, J = 1.83, 8.70 Hz, 1H), 7.45 (dd, J = 1.83, 11.75 Hz, 1H), 7.23 (t, J = 8.54, 1H), 4.29 (s, 2H), 3.10 (s, 3H). LC-MS (m/z): 205.1 [M+H]+.

Reference： [1]Patent: WO2007/54668,2007,A1 .Location in patent: Page/Page column 9-10
[2]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 529 - 532

7
[ 67-56-1 ]
[ 424792-57-4 ]
[ 20951-14-8 ]

Yield	Reaction Conditions	Operation in experiment
94%	With potassium hydroxide; In water; for 3h;Heating / reflux;	2. Preparation of 2-Fluoro- 1 -methoxy-4-(methylsulfonyl)benzene 2009330; Carried out over two equal batches. A solution of 85% potassium hydroxide (824 g, 12.51 mol) in methanol (5 L) was added in 500 niL portions over a period of 2 h to a refluxing solution of l,2-difluoro-4-(methylsulfonyl)benzene 2008101 (2.00 kg, 10.4 mol) in methanol (5 L). Upon complete addition, the reaction mixture was heated at reflux for a further 1 h before being allowed to cool to room temperature. The mixture was then concentrated under reduced pressure and water (10 L) was added to the residue. The resultant precipitate was collected by filtration, washed with water (5 L) and dried to give 2-fluoro-l-methoxy-4-(methylsulfonyl)benzene 2009330 (2.0 kg, 94%) as a white solid, mp 98-1010C. 1H NMR (300 MHz, CDCl3) delta 3.05 (s, 3H), 3.96 (s, 3H), 7.09 (app t, IH), 7.63 (dd, IH), 7.70 (dd, IH).
85%	With potassium hydroxide; for 1.33333h;Reflux;	Step 2: 2-Fluoro-4-methanesulfonyl-1-methoxy-benzene; A solution of potassium hydroxide (85%; 824 mg, 12.5 mmol) in methanol (5 mL) was added to a refluxing solution of <strong>[424792-57-4]1,2-difluoro-4-methanesulfonyl-benzene</strong> (2.00 g, 10.4 mmol) in methanol (10 mL) over 20 min. The resulting mixture was heated at reflux for 1 h and then cooled to room temperature. The solvent was evaporated, water was added, and the resulting precipitate was filtered off, washed with water, and dried in vacuo to give 2-fluoro-4-methanesulfonyl-1-methoxy-benzene (1.8 g, 85%) as a white solid which was used directly in the next step without purification.

Reference： [1]Patent: WO2007/54668,2007,A1 .Location in patent: Page/Page column 11
[2]Patent: US2009/286812,2009,A1 .Location in patent: Page/Page column 18

8
[ 424792-57-4 ]
[ 104706-47-0 ]
[ 1054521-30-0 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In N,N-dimethyl-formamide; at 100℃;	Example 2; (S)-isopropyl 4-(3-(l-(2-fluoro-4-(methylsulfonyl)phenyl)pyrrolidin-3-yl)-l,2,4-oxadiazol-5- vDpiperidine- 1 -carboxylate; [0092] Intermediate 2a: (R)-l-(2-fluoro-4-(methylsulfonyl)phenyl)pyrrolidin-3-ol; [0093] A mixture of <strong>[424792-57-4]1,2-difluoro methyl sulfonyl benzene</strong> (2.484 g, 12.92 mmol), 3-(/?)-hydroxypyrrolidine hydrochloride (1.917 g, 15.51 mmol), and K2CO3 (4.47 g, 32.31 mmol) in DMF (13 mL) is heated to 1000C and maintained overnight. The reaction is poured over H2O and extracted with EtOAc. The organics were pooled, dried (MgSO4), filtered and concentrated. The crude material was purified via SiO2 chromatography (ISCO, 0-80%, EtOAc in Hexanes) to afford the title compound. 1H NMR (400 MHz, CDCl3) delta 7.49 (m, 2H), 6.63 (dd, J = 8.6, 8.5 Hz, IH), 4.59 (m, IH), 3.73 (m, 2H), 3.52 (m, 2H), 3.00 (s, 3H), 2.08 (m, 2H); LC/MS calcd. for [M+H]+ CnH15FNO3S: 260.3, found: 260.0.
	With potassium carbonate; In N,N-dimethyl-formamide; at 100℃;	A mixture of <strong>[424792-57-4]1,2-difluoro methyl sulfonyl benzene</strong> (2.484 g, 12.92 mmol), 3-(R)- hydroxypyrrolidine hydrochloride (1.917 g, 15.51 mmol), and K2CO3 (4.47 g, 32.31 <n="27"/>mmol) in DMF (13 niL) was heated to 1000C and maintained overnight. The reaction was poured over H2O and extracted with EtOAc. The organics were pooled, dried (MgSO4), filtered and concentrated. The crude material was purified via SiO2 chromatography (ISCO, 0-80%, EtOAc in Hexanes) to afford the alcohol. 1H NMR (400 MHz, CDCl3) delta 7.49 (m, 2H), 6.63 (dd, J = 8.6, 8.5 Hz, IH), 4.59 (m, IH), 3.73 (m, 2H), 3.52 (m, 2H), 3.00 (s, 3H), 2.08 (m, 2H); ESIMS calcd. for [M+H]+ C11H15FNO3S: 260.3, found: 260.0.A sample of the intermediate alcohol (1 g, 3.9 mmol) was treated with dichloromethane (30 mL) and pyridine (915 mg, 11.6 mmol). The reaction was then treated with methanesulfonyl chloride (663 mg, 5.8 mmol) and stirred overnight. The reaction was diluted with ethyl acetate and extracted with 1 M HCl twice. The organics were dried over MgSO4, filtered, evaporated and purified over silica gel using a linear gradient of 0 to 100% ethyl acetate in hexane to afford 2b; ESIMS m/z for (M+ + H+) Ci2Hi6FNO5S2 calcld. 338.1, found 338.2.

Reference： [1]Patent: WO2008/109702,2008,A1 .Location in patent: Page/Page column 25
[2]Patent: WO2009/105715,2009,A1 .Location in patent: Page/Page column 25-26

9
[ 424792-57-4 ]
[ 1054521-44-6 ]
[ 1054521-08-2 ]

Yield	Reaction Conditions	Operation in experiment
		A sample of intermediate 10b (36.1 mg, 0.088 mmol) is treated with a 4M solution of HCl in dioxane and stirred for 1.5 hours. The solvent is then removed and the residue is treated with l,2-difluoro-4-(methylsulfonyl)benzene (17 mg, 0.88 mmol), K2CO3 (36.6 mg, 0.27 mmol) and DMF (1 mL) and heated to 100 0C overnight. The reaction is poured into water and extracted with ethyl acetate twice. The combined organics are dreid over MgSO4, evaporated and purified by preperative mass directed HPLC to afford (S)- isopropyl 4-(5-(l-(2-fluoro-4-(methylsulfonyl)phenyl)pyrrolidin-3-yl)-l,3,4-oxadiazol-2- yl)piperidine-l-carboxylate. 1H NMR (400 MHz, CDCl3) delta 7.54 (m, 2H), 6.68 (dd, J = 8.5, 8.4 Hz, IH), 4.93 (sept., 7 = 6.2 Hz, IH), 4.16 (d, J = 10.6 Hz, 2H), 3.96 (m, IH), 3.89 (m, IH), 3.72 (m, 3H), 3.09 (m, IH), 3.02 (s, 3H), 2.98 (m, 2H), 2.47 (m, 2H), 2.07 (m, 2H), 1.82 (m, 2H), 1.25 (d, J = 6.2 Hz, 6H); ESIMS m/z for (M+H)+ C22H30FN4O5S calcd.: 481.6 found: 481.2.

Reference： [1]Patent: WO2008/109702,2008,A1 .Location in patent: Page/Page column 32

10
[ 424792-57-4 ]
[ 1104452-52-9 ]
[ 1104452-50-7 ]

Yield	Reaction Conditions	Operation in experiment
		A suspension of 4-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one (127 mg, 0.424 mmol, prepared according to procedures described in Example 230 Step C substituting 2-chloro-5-ethylpyrimidine (Aldrich) for 2-chloro-5-cyclopropylpyrimidine), sodium hydride (60 wt % mineral oil, 21 mg, 0.51 mmol) and DMF (5 mL) was purged with Argon and then stirred at room temperature for 1 h. To the reaction was added <strong>[424792-57-4]1,2-difluoro-4-(methylsulfonyl)benzene</strong> (90 mg, 0.47 mmol, Matrix Scientific) and then heated at 110 C. for 1 h. The resulting mixture was quenched with H2O and extracted with EtOAc. The organic layer was concentrated in vacuo to a yellow solid. The solid was purified by flash chromatography (SiO2, 0 to 100% EtOAc in CH2Cl2) to yield 91 mg of the desired product as an off-white solid. 1H NMR (400 MHz, CDCl3) delta ppm 8.20 (s, 2 H), 7.83-7.91 (m, 2 H), 7.64 (dd, J=8.53, 6.78 Hz, 1 H), 7.13 (dd, J=7.53, 1.00 Hz, 1 H), 6.08 (dd, J=7.65, 2.64 Hz, 1 H), 6.03 (d, J=2.51 Hz, 1 H), 4.54-4.63 (m, 1 H), 4.16-4.27 (m, 2 H), 3.60-3.70 (m, 2 H), 3.12 (s, 3 H), 2.49 (q, J=7.53 Hz, 2 H),1.97-2.15 (m, 2 H),1.78-1.97 (m, 2 H),1.21 (t, J=7.53 Hz, 3 H). MS (ESI) 473 (M+H).

Reference： [1]Patent: US2009/23702,2009,A1 .Location in patent: Page/Page column 120

11
[ 424792-57-4 ]
[ 53937-02-3 ]
[ 1104448-45-4 ]

Yield	Reaction Conditions	Operation in experiment
52%		To 4-(benzyloxy)pyridin-2(1H)-one (6.12 g, 30.4 mmol) in a 500 mL recovery flask was applied vacuum for 5 minutes then placed under an atmosphere of nitrogen and added DMF (100 mL) to produce a suspension. Added NaH (60% in oil) (1.271 g, 31.8 mmol) over 10 minutes as a slow evolution of gas was observed. By 60 minutes, the tan suspension had become thicker and lighter in color. After 60 minutes added 1,2-difluoro-4-(methylsulfonylbenzene (5.31 g, 27.6 mmol) and placed the reaction mixture in a 110 C. oil bath under nitrogen for 70 minutes to produce a tan suspension. Added 400 mL of water and 400 mL of EtOAc to the reaction, removed aqueous layer, washed organic layer with 400 mL of brine, dried with MgSO4, filtered and concentrated to give 12 g pale yellow powder. This was purified by flash chromatography (0.75-1.00% MeOH/CH2Cl2) followed by recrystallization from EtOAc to yield 5.39 g (14.4 mmol, 52% yield) of product as a white powder. MS (ESI) 374.4 (M+1).

Reference： [1]Patent: US2009/23702,2009,A1 .Location in patent: Page/Page column 90
[2]Journal of Medicinal Chemistry,2014,vol. 57,p. 7499 - 7508

12
[ 75-75-2 ]
[ 367-11-3 ]
[ 424792-57-4 ]

Yield	Reaction Conditions	Operation in experiment
59%		Step 1: 1,2-Difluoro-4-methanesulfonyl-benzene; A mixture of thionyl chloride (12.73 mL, 0.175 mol) and methanesulfonic acid (28.4 mL, 0.438 mol) was heated at reflux overnight and then cooled to 80 C. 1,2-Difluorobenzene (8.64 mL, 88 mmol) was and trifluoromethanesulfonic acid (0.675 mL, 8.8 mmol) were added dropwise. The reaction mixture was then heated at 120 C. for 3 h, cooled to room temperature and poured into ice-water (200 mL). The mixture was extracted three times with ethyl acetate and the combined organic extracts were dried (sodium sulfate), filtered, evaporated, and purified by flash chromatography, eluting with 15% ethyl acetate/hexanes, to give 1,2-difluoro-4-methanesulfonyl-benzene (9.98 g, 59%) as a white solid. 1H NMR (300 MHz, CDCl3) delta 3.27 (s, 3H), 7.70-7.84 (m, 2H), 8.02-8.09 (m, 1H).
46 - 48%		EXAMPLE 1; Preparation of r2-Fluoro-4-(methylsulfonv?phenyl]hvdrazine (2008180); 2008101 <n="10"/>1. Preparation of 1 ,2-Difluoro-4-(methylsulfongammaDbenzene (2008101)2008101A mixture of methanesulfonic acid (22.18 kg, 230.78 mol) and thionyl chloride (11.00 kg, 89.66 mol) was carefully heated to 9O0C over 10 h (a scrubber containing dilute sodium hydroxide solution was used to prevent emission of corrosive gases) and then maintained at 9O0C overnight. The resultant solution was then heated to 12O0C and a solution of 1,2- difluorobenzene (5.263 kg, 46.17 mol) and trifluoroniethanesulfonic acid (0.71 kg, 4.71 mol) was added dropwise over 2 h at 115-12O0C. Upon complete addition the reaction mixture was heated at 12O0C for a further 4 h, cooled to 500C, and divided into 2 equal portions. Each portion was carefully added to water (50 kg) at 5O0C, causing the temperature of the mixture to rise to ca.70 0C. The mixture was then cooled to 35C and the product was extracted with dichloromethane (9.47 kg). The combined organic fractions derived from the two portions were separated, dried, and concentrated to a thick slush. Hexane (3.19 kg) was added and the resultant precipitate was collected by filtration, washed with hexane (1.6 kg), and dried in air to give l,2-difluoro-4- (methylsulfonyl)benzene (2008101) (4.23 kg, 48 %) as a white solid, m.p. 1 A-ITQ.; EXAMPLE 2; Preparation of 2-Fluoro-(4-methylsulfonyl)phenol 2020463; 2008101; 1. Preparation of l,2-Difluoro-4-(methylsulfonvDbenzene 2008101; Carried out over two equal batches. Thionyl chloride (2.92 kg, 24.6 mol) and methanesulfonic acid (5.90 kg, 61.4 mol) were heated at reflux overnight in the presence of a scrubber. The reaction mixture was then cooled to 80C, 1,2-difluorobenzene (1.40 kg, 12.3 mol) and trifluomethanesulfonic acid (110 mL, 1.22 mol) were added, and the resultant reaction mixture was heated at 12O0C for 3 h before being allowed to cool to room temperature. The reaction was then poured onto a mixture of ice/water (40 L), the resultant precipitate was collected by filtration, washed with water, and recrystallised <n="12"/>from isopropyl alcohol (2.5 L) to give l,2-difluoro-4-(methylsulfonyl)benzene 2008101 (1.08 kg, 46%) as a white solid, mp 72-74C.

Reference： [1]Patent: US2009/286812,2009,A1 .Location in patent: Page/Page column 18
[2]Patent: WO2007/54668,2007,A1 .Location in patent: Page/Page column 8-9; 10-11

13
[ 424792-57-4 ]
[ 1259508-82-1 ]
[ 76-05-1 ]
4-[1(2-fluoro-4-methanesulfonylphenyl)piperidin-4-ylideneaminooxy]piperidine-1-carboxylic acid isopropyl ester trifluoroacetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Step 2E: 4-ri-(2-Fluoro-4-methanesulfonyl-phenyl)-piperidin-4-ylideneaminooxyl- piperidine-1-carboxylic acid isopropyl ester (2-1)Compound 2d (24 mg, 0.085 mmol), l,2-difluoro-4-methanesulfonyl-benzene (0.13 mmol), DIEA (0.075 mL, 0.45 mmol), and DMSO (0.3 mL) were combined and heated at 130 0C for 20 h. The mixture was cooled to room temperature, methanol (0.75 mL) was added, and the mixture was purified by preparative HPLC to afford the trifluoroacetic acid salt of 2-1.

Reference： [1]Patent: WO2010/149684,2010,A1 .Location in patent: Page/Page column 59

14
[ 5382-16-1 ]
[ 424792-57-4 ]
[ 887453-50-1 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate; In N,N-dimethyl-formamide; at 60℃; for 18h;	Step IA: l-(2-Fluoro-4-methanesulfonyl-phenyl)-piperidin-4-ol (Ia)4-Hydroxypyridinol (658 mg, 6.5 mmol) and l,2-difluoro-4-(methanesufonyl)benzene (1.98 g, 5.1 mmol) were combined in DMF (5 mL). Sodium carbonate (705 mg, 6.7 mmol) was added and the mixture was heated at 60 0C for 18 h. The mixture was cooled to room temperature and then poured into a mixture of water (10 mL) and a saturated sodium chloride solution (10 mL). The mixture was extracted three times with ethyl acetate (15 mL) and the extracts were combined, washed with brine, dried (MgSO4), and concentrated under vacuum to afford 1.46 g of crude Ia, which was used in the subsequent step without purification: LC-MS 274.1 (MH+).

Reference： [1]Patent: WO2010/149684,2010,A1 .Location in patent: Page/Page column 56

15
[ 424792-57-4 ]
[ 1259508-78-5 ]

Reference： [1]Patent: WO2010/149684,2010,A1

16
[ 424792-57-4 ]
4-[1-(2-fluoro-4-methanesulfonylphenyl)piperidin-4-ylideneaminooxy]piperidine-1-carboxylic acid tert-butyl ester trifluoroacetate [ No CAS ]

Reference： [1]Patent: WO2010/149684,2010,A1

17
[ 424792-57-4 ]
[ 1293319-49-9 ]
[ 1293319-33-1 ]

Reference： [1]Tetrahedron Letters,2011,vol. 52,p. 1949 - 1951

18
[ 424792-57-4 ]
[ 1293319-43-3 ]
[ 1293319-32-0 ]

Reference： [1]Tetrahedron Letters,2011,vol. 52,p. 1949 - 1951

19
[ 424792-57-4 ]
tetrabutylammonium 4-(1-(t-butoxycarbonyl)piperidin-4-yloxy)-5-chloropyridin-2-olate [ No CAS ]
[ 1339944-38-5 ]

Yield	Reaction Conditions	Operation in experiment
70%	In 1-methyl-pyrrolidin-2-one; at 80℃; for 12h;Inert atmosphere;	Step C: Preparation of tert-butyl 4-(5-chloro-1-(2-fluoro-4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate A two liter round bottom flask was charged with tetrabutylammonium 4-(1-(t-butoxycarbonyl)piperidin-4-yloxy)-5-chloropyridin-2-olate (90 g, 158 mmol), NMP (500 mL), and <strong>[424792-57-4]1,2-difluoro-4-(methylsulfonyl)benzene</strong> (30.3 g, 158 mmol). The mixture was heated to 80 C. under nitrogen for 12 hours. After cooling to room temperature, the reaction was diluted with ethyl acetate (500 mL) and distilled water (500 mL). The organic layer was separated, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. To the residue was added 500 mL of 20% ethyl acetate in diethyl ether and the mixture was stirred for 12 hours at room temperature. The slurry was then cooled to 4 C. and stirring was continued for additional 1 hour. The solid was collected by filtration and dried under vacuum for 4 hours at 45 C. to yield t-butyl 4-(5-chloro-1-(2-fluoro-4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate (58 g, 70% yield) as a white solid. 1H-NMR (CDCl3, 400 MHz) delta 7.85-7.89 (m, 1H), 7.61-7.64 (m, 1H), 7.32 (s, 1H), 6.02 (s, 1H), 4.57-4.63 (m, 1H), 3.59-3.69 (m, 2H), 3.44-3.55 (m, 2H), 3.11 (s, 3H), 1.83-2.05 (m, 4H), 1.48 (s, 9H); MS nee 501.2 (M+H+).

Reference： [1]Patent: US2011/251221,2011,A1 .Location in patent: Page/Page column 15

20
[ 424792-57-4 ]
[ 1339944-31-8 ]
[ 1339944-43-2 ]

Yield	Reaction Conditions	Operation in experiment
37%		Example 2 5-Chloro-1-(2-fluoro-4-(methylsulfonyl)phenyl)-4-(1-(5-(trifluoromethyl)pyrimidin-2-yl)piperidin-4-yloxy)pyridin-2 (1H) -oneTo a 4 mL vial was added a 60% oil dispersion of sodium hydride (53 mg, 1.33 mmol), DMF (10 mL), and Intermediate 3 (250 mg, 0.67 mmol). The mixture was stirred at room temperature for 30 minutes and then <strong>[424792-57-4]1,2-difluoro-4-(methylsulfonyl)benzene</strong> (192 mg, 1.00 mmol) was added. The mixture was heated at 100 C. for 12 hours. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate (40 mL) and washed with water three times. The organic layer was collected, dried over sodium sulfate, and filtered. The residue obtained was purified by flash chromatography (silica gel, 0-100% ethyl acetate /hexane) to give Example 2 (139 mg, 37% yield) as a yellow solid. 1H NMR (DMSO-d6, 500 MHz) delta 8.72 (2H, s), 8.11 (1H, s), 7.97-8.06 (1H, m), 7.78-7.95 (2H, m), 6.31 (1H, s), 4.90-5.01 (1H, m), 4.06-4.22 (2H, m), 3.74-3.89 (2H, m), 3.36 (3H, s), 1.98-2.16 (2H, m), 1.62-1.83 (2H, m) ; MS (ESI) 547.1 (M+H).

Reference： [1]Patent: US2011/251221,2011,A1 .Location in patent: Page/Page column 17
[2]Journal of Medicinal Chemistry,2014,vol. 57,p. 7499 - 7508

21
[ 424792-57-4 ]
[ 1351168-81-4 ]
[ 1351168-82-5 ]

Yield	Reaction Conditions	Operation in experiment
16%	With sodium carbonate; In dimethyl sulfoxide; at 120℃;Inert atmosphere;	Step E: tert-Butyl 4-((S)-3-amino-2-oxopyrrolidin-l-yl)-3,3- dimethylpiperidine-l-carboxylate (0.40 g, 1.3 mmol) was dissolved in DMSO (5 mL). 1,2- Difluoro-4-(methylsulfonyl)benzene (0.32 g, 1.7 mmol) and powdered a2C03 (0.18 g, 1.7 mmol) were added. The reaction mixture was bubbled under nitrogen for 15 minutes. The mixture stirred overnight at 120 C. The reaction mixture was cooled to ambient temperature and partitioned between brine and ethyl acetate. The organic layer was washed with brine, dried over MgS04, and concentrated. Flash chromatography of the crude material on silica gel followed by reverse phase HPLC purification gave tert-butyl 4-((S)-3-(2-fluoro-4- (methylsulfonyl)phenylamino)-2-oxopyrrolidin- 1 -yl)-3 ,3 -dimethylpiperidine- 1 -carboxylate (0.10 g, 0.21 mmol, 16% yield) as a white solid.

Reference： [1]Patent: WO2011/146335,2011,A1 .Location in patent: Page/Page column 138

22
[ 424792-57-4 ]
[ 1351167-90-2 ]
[ 1351167-91-3 ]

Yield	Reaction Conditions	Operation in experiment
42%	With sodium carbonate; In dimethyl sulfoxide; at 120℃; for 48h;	Step E: A solution of (S)-benzyl 4-(3-amino-2-oxopyrrolidin-l-yl)piperidine-1-carboxylate (2.0 g, 6.3 mmol), l,2-difluoro-4-(methylsulfonyl)benzene (1.2 g, 6.3 mmol), and Na2C03 (3.3 g, 32 mmol) in DMSO (20 mL) was stirred at 120 C for 48 hours. The reaction mixture was poured into water (200 mL) and extracted with EtOAc (3 x 100 mL). The combined organic layers were washed with brine and dried over MgS04, filtered then concentrated in vacuo. The material was purified over silica gel (100% EtOAc) to yield (S)- benzyl 4-(3-(2-fluoro-4-(methylsulfonyl)phenylamino)-2-oxopyrrolidin-l-yl)piperidine-l- carboxylate (1.3 g, 2,7 mmol, 42%).
42%	With sodium carbonate; In dimethyl sulfoxide; at 120℃; for 48h;	[00384] Step E: A solution of (S)-benzyl 4-(3-amino-2-oxopyrrolidin-l-yl)piperidine-1-carboxylate (2.0 g, 6.3 mmol), l,2-difluoro-4-(methylsulfonyl)benzene (1.2 g, 6.3 mmol), and Na2C03 (3.3 g, 32 mmol) in DMSO (20 mL) was stirred at 120 C for 48 hours. The reaction mixture was poured into water (200 mL) and extracted with EtOAc (3 x 100 mL). The organic layer was washed with brine, dried over MgS04 and then concentrated under vacuum. The material was purified over silica gel (100% EtOAc) to yield (S)-benzyl 4-(3-(2- fluoro-4-(methylsulfonyl)phenylamino)-2-oxopyrrolidin-l-yl)piperidine-l-carboxylate (1.3 g, 2,7 mmol, 42%).
42%	With sodium carbonate; In dimethyl sulfoxide; at 120℃; for 48h;	A solution of (S)-benzyl 4-(3-amino-2-oxopyrrolidin-l-yl)piperidine- 1-carboxylate (2.0 g, 6.3 mmol), l,2-difluoro-4-(methylsulfonyl)benzene (1.2 g, 6.3 mmol), and Na2C03 (3.3 g, 32 mmol) in DMSO (20 mL) was stirred at 120 C for 48 hours. The reaction mixture was poured into water (200 mL) and extracted with EtOAc (3 x 100 mL). The combined organic layers were washed with brine, dried over MgS04, filtered and concentrated in vacuo. The material was purified over silica gel (100% EtOAc) to yield (S)- benzyl 4-(3-(2-fluoro-4-(methylsulfonyl)phenylamino)-2-oxopyrrolidin-l-yl)piperidine-l- carboxylate (1.3 g, 2,7 mmol, 42%).

Reference： [1]Patent: WO2011/146335,2011,A1 .Location in patent: Page/Page column 62
[2]Patent: WO2012/37393,2012,A1 .Location in patent: Page/Page column 52
[3]Patent: WO2013/66869,2013,A1 .Location in patent: Paragraph 00419

23
[ 424792-57-4 ]
[ 851120-63-3 ]
[ 1365998-48-6 ]

Yield	Reaction Conditions	Operation in experiment
43.1%	With sodium carbonate; In dimethyl sulfoxide; at 120℃;Inert atmosphere;	[00394] Step D: (S)-tert-Butyl 3 -amino-2-oxo-l,4'-bipiperidine-l '-carboxylate (1.0 g,3.36 mmol) was dissolved in DMSO (20 mL) and l,2-difluoro-4-(methylsulfonyl)benzene (0.775 g, 4.04 mmol) and a2C03 (0.535 g, 5.04 mmol) were added and the reaction heated to 120 C under nitrogen overnight. The reaction was cooled to ambient temperature, water was added and the reaction mixture was extracted with EtOAc, dried over Na2S04, filtered and concentrated under vacuum. The residue was purified over silica gel (80% EtOAc in hexanes) to afford (S)-tert-butyl 3-(2-fluoro-4-(methylsulfonyl)phenylamino)-2-oxo-l,4'- bipiperidine-l'-carboxylate (680 mg, 1.45 mmol, 43.1% yield) as a white solid. Mass spectrum (apci) m/z = 370.2 (M+H-Boc).
43.1%	With sodium carbonate; In dimethyl sulfoxide; at 120℃;Inert atmosphere;	Step D: (S)-tert-butyl 3-amino-2-oxo-l,4'-bipiperidine- -carboxylate (1.0 g, 3.36 mmol) was dissolved in DMSO (20 mL). l,2-dif uoro-4-(methylsulfonyl)benzene (0.775 g, 4.04 mmol) and Na2C03 (0.535 g, 5.04 mmol) were added and the reaction was heated to 120 C under nitrogen overnight. The reaction was cooled to ambient temperature, water added and extracted with EtOAc , dried over Na2S04 , filtered and concentrated. The residue was purified over silica gel (80%> EtOAc in hexanes) to afford (S)-tert-butyl 3-(2- f uoro-4-(methylsulfonyl)phenylamino)-2-oxo-l,4'-bipiperidine- -carboxylate (680 mg, 1.45 mmol, 43.1 %> yield) as a white solid. Mass spectrum (apci) m/z = 370.2 (M+H-Boc).

Reference： [1]Patent: WO2012/37393,2012,A1 .Location in patent: Page/Page column 55
[2]Patent: WO2013/66869,2013,A1 .Location in patent: Paragraph 00429

24
[ 424792-57-4 ]
[ 2785-89-9 ]
C₁₆H₁₇FO₄S [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 9914 - 9928

25
[ 424792-57-4 ]
[ 2785-89-9 ]
[ 1403681-74-2 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 9914 - 9928

26
2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole [ No CAS ]
[ 424792-57-4 ]
C₁₂H₁₂FN₃O₂S [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 194 - 197

27
2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole [ No CAS ]
[ 424792-57-4 ]
[ 1416137-40-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 194 - 197

28
[ 424792-57-4 ]
[ 1280210-79-8 ]
[ 1416137-42-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 194 - 197

29
[ 424792-57-4 ]
[ 1072-84-0 ]
[ 1415836-80-4 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 120℃;	Intermediate 641 -(2-Fluoro-4-methanesulfonylphenyl)-1 H-<strong>[1072-84-0]imidazole-4-carboxylic acid</strong>A mixture of 1 H-<strong>[1072-84-0]imidazole-4-carboxylic acid</strong> (500 mg), 1 ,2-difluoro-4- methanesulfonylbenzene (1 .2 g), and N,N-diisopropyl-ethyl-amine (4 mL) in N,N- dimethylformamide (6 mL) is heated to 120 °C overnight. The crude product is purified by HPLC. LC (method 20): tR = 1 .69 min; Mass spectrum (APCI): m/z = 285 [M+H]+.
	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 120℃;	1-(2-Fluoro-4-methanesulfonylphenyl)-1H-<strong>[1072-84-0]imidazole-4-carboxylic acid</strong> A mixture of 1H-<strong>[1072-84-0]imidazole-4-carboxylic acid</strong> (500 mg), 1,2-difluoro-4-methanesulfonylbenzene (1.2 g), and N,N-diisopropyl-ethyl-amine (4 mL) in N,N-dimethylformamide (6 mL) is heated to 120° C. overnight. The crude product is purified by HPLC. LC (method 20): tR=1.69 min; Mass spectrum (APCI): m/z=285 [M+H]+.

Reference： [1]Patent: WO2012/168315,2012,A1 .Location in patent: Page/Page column 104
[2]Patent: US2013/143892,2013,A1 .Location in patent: Paragraph 0390; 0391

30
[ 424792-57-4 ]
[ 1457-58-5 ]
[ 1415836-83-7 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 120℃;	Intermediate 661 -(2-Fluoro-4-methanesulfonylphenyl)-2-methyl-1 H-imidazole-4-carboxylic acidA mixture of 2-methyl-1 H-imidazole-4-carboxylic acid (500 mg), N,N-diisopropyl- ethyl-amine (4 mL), and 1 ,2-difluoro-4-methanesulfonylbenzene (1 .2 g), in N,N- dimethylformamide (6 mL) is heated to 120 C overnight. The crude product is purified by HPLC. LC (method 20): tR = 0.90 min; Mass spectrum (APCI): m/z = 299 [M+H]+.
	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 120℃;	1-(2-Fluoro-4-methanesulfonylphenyl)-<strong>[1457-58-5]2-methyl-1H-imidazole-4-carboxylic acid</strong> A mixture of <strong>[1457-58-5]2-methyl-1H-imidazole-4-carboxylic acid</strong> (500 mg), N,N-diisopropyl-ethyl-amine (4 mL), and 1,2-difluoro-4-methanesulfonylbenzene (1.2 g), in N,N-dimethylformamide (6 mL) is heated to 120 C. overnight. The crude product is purified by HPLC. LC (method 20): tR=0.90 min; Mass spectrum (APCI): m/z=299 [M+H]+.

Reference： [1]Patent: WO2012/168315,2012,A1 .Location in patent: Page/Page column 105
[2]Patent: US2013/143892,2013,A1 .Location in patent: Paragraph 0396; 0397

31
[ 424792-57-4 ]
[ 1433890-51-7 ]
[ 1433879-86-7 ]

Yield	Reaction Conditions	Operation in experiment
54%	With sodium carbonate; In dimethyl sulfoxide; at 120℃; for 72h;	Step E: (S)-3-Amino-l-(l-(3-isopropyl-l,2,4-thiadiazol-5-yl)piperidin-4- yl)pyrrolidin-2-one (500 mg, 1.62 mmol) was dissolved in DMSO (8 mL) and 1 ,2-difluoro-4- (methylsulfonyl)benzene (621 mg, 3.23 mmol) and Na2C03 (171 mg, 1.62 mmol) were added. The reaction was heated to 120 C for 3 days. The reaction was partitioned between water and EtOAc and extracted with EtOAc. The combined organic layers were dried over Na2S04, filtered and concentrated. The residue was purified over silica gel (0 to 5% methanol in EtOAc) to afford (S)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)-l-(l-(3-isopropyl-l,2,4- thiadiazol-5-yl)piperidin-4-yl)pyrrolidin-2-one (420 mg, 0.872 mmol, 54.0 % yield) as a tan solid. Mass spectrum (apci) m/z = 482.2 (M+H).

Reference： [1]Patent: WO2013/66869,2013,A1 .Location in patent: Paragraph 00435

32
[ 424792-57-4 ]
[ 1104448-50-1 ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 7499 - 7508

33
[ 424792-57-4 ]
[ 1104448-54-5 ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 7499 - 7508

34
[ 424792-57-4 ]
[ 1339944-36-3 ]
[ 1339944-38-5 ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 7499 - 7508

35
[ 424792-57-4 ]
N5-((2-fluoro-4-(methylsulfonyl)phenyl)amino)-L-glutamine [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 529 - 532

36
[ 424792-57-4 ]
benzyl N2-((benzyloxy)carbonyl)-N5-((2-fluoro-4-(methylsulfonyl)phenyl)amino)-L-glutaminate [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 529 - 532

37
[ 424792-57-4 ]
[ 1054521-34-4 ]