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[ CAS No. 473923-95-4 ] {[proInfo.proName]}

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Chemical Structure| 473923-95-4
Chemical Structure| 473923-95-4
Structure of 473923-95-4 * Storage: {[proInfo.prStorage]}
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Product Details of [ 473923-95-4 ]

CAS No. :473923-95-4 MDL No. :MFCD09972133
Formula : C7H4FNO Boiling Point : -
Linear Structure Formula :- InChI Key :ATVNHLQIIAOSEM-UHFFFAOYSA-N
M.W : 137.11 Pubchem ID :21949920
Synonyms :

Calculated chemistry of [ 473923-95-4 ]

Physicochemical Properties

Num. heavy atoms : 10
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.0
Num. rotatable bonds : 0
Num. H-bond acceptors : 3.0
Num. H-bond donors : 1.0
Molar Refractivity : 33.14
TPSA : 44.02 Ų

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 : Yes
Log Kp (skin permeation) : -6.15 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.26
Log Po/w (XLOGP3) : 1.39
Log Po/w (WLOGP) : 1.82
Log Po/w (MLOGP) : 1.22
Log Po/w (SILICOS-IT) : 1.74
Consensus Log Po/w : 1.49

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.01
Solubility : 1.34 mg/ml ; 0.00978 mol/l
Class : Soluble
Log S (Ali) : -1.92
Solubility : 1.66 mg/ml ; 0.0121 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -2.16
Solubility : 0.955 mg/ml ; 0.00697 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.41

Safety of [ 473923-95-4 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P280-P305+P351+P338 UN#:N/A
Hazard Statements:H317-H319 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 473923-95-4 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 473923-95-4 ]

[ 473923-95-4 ] Synthesis Path-Downstream   1~85

YieldReaction ConditionsOperation in experiment
Preparation 71 3-[(1-Acetyl-3,5-dimethyl-1H-pyrazol-4-yl)oxy]-5-fluorobenzonitrile The phenol from Preparation 34 (10.0 g, 72.7 mmol), 3-chloro-2,4-pentanedione (7.10 g, 72.7 mmol) and cesium carbonate (23.6 g, 72.9 mmol) were heated to reflux in acetone (100 ml) under nitrogen for 2 hours. The reaction was cooled to room temperature, 1N aqueous hydrochloric acid (50 ml) was added slowly and the mixture was extracted with ethyl acetate (3*100 ml). The combined organic extracts dried over magnesium sulphate and concentrated under reduced pressure. The residual yellow oil was dissolved in methanol (100 ml), hydrazine (5.3 ml, 109 mmol) was added and the reaction was stirred at room temperature under nitrogen for 2 hours. The solvent was removed under reduced pressure and the residue was dissolved in dimethylformamide (50 ml) at 0 C. Acetyl chloride (5.1 ml, 72.0 mmol) was added slowly followed by sodium hydride (60% dispersion in oil, 2.8 g, 72.0 mmol) portionwise. The reaction was stirred for 15 minutes and sat. ammonium chloride solution (50 ml) was added, and the reaction was allowed to warm to room temperature. The mixture was extracted with ethyl acetate (3*100 ml) and the combined organic extracts were dried over magnesium sulphate and concentrated under reduced pressure giving an oil.
  • 2
  • [ 473923-95-4 ]
  • [ 1138423-45-6 ]
  • [ 911405-96-4 ]
YieldReaction ConditionsOperation in experiment
Intermediate (R) -1-1 d (20.0 mg, 0.0626 mmol) and 3-fluoro-5-hydroxy-benzonitriIe (17.1mg, 0.125) was dissolved in 1 mL anhydrous THF in a predried reaction vial under N2 atmosphere. Polymer bound triphenylphosphine (57.1mg, 2.19mmol/g loaded, 0.125mmol) was then added and the mixture allowed to stir at room temperature for 30 minutes. The EPO <DP n="45"/>reaction was cooled to 0 SC, DEAD (40% in toluene, 56.8 mul_, 0.125 mmol) was added, and reaction mixture was allowed to reach room temperature overnight. The resin was filtered off washing with THF, the solvent removed in vacuo, and then the residue was purified by preparative (eluting with TLC 20% EtOAc/Hexane) to afford the BOC-protected 3-fluoro-5- [(7S)-2-piperazin-1-yl-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl]oxy}benzonitrile.
  • 3
  • [ 473923-95-4 ]
  • [ 317356-84-6 ]
  • [ 1048979-59-4 ]
  • 4
  • [ 13054-81-4 ]
  • [ 473923-95-4 ]
  • [ 473923-99-8 ]
  • 5
  • [ 473923-95-4 ]
  • 3-fluoro-5-hydroxybenzaldehyde [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% With diisobutylaluminium hydride; In toluene; at -78 - 20℃; for 1.0h; Step 1. 3-Fluoro-5-hydroxybenzaldehyde To a suspension of <strong>[473923-95-4]3-fluoro-5-hydroxybenzonitrile</strong> (1.00 g, 7.29 mmol) in toluene (60.0 mL at -78 C was added 1.0 M diisobutylaluminum hydride in toluene (18.2 mL, 18.2 mmol). The resulting mixture was stirred at -78 C for 1 hour and allowed to warm to room temperature overnight. The 1 : 1 mixture of methanol and water (10 mL) was added and stirred for 35 minutes. The solid was filtered and washed with ethyl acetate. The filtrates were washed with water and brine then dried over Na2S04, filtered, and concentrated. The crude product was purified with silica gel column (eluted with 10-50% ethyl acetate/hexanes) to give the desired product (0.77 g, 75%). 1H NMR (DMSO-d6) delta 10.49 (s, 1H), 9.88 (s, 1H), 7.10 (m, 2H), 6.87 (d, 1H).
75% Step 1. 3-Fluoro-5-hydroxybenzaldehyde To a suspension of <strong>[473923-95-4]3-fluoro-5-hydroxybenzonitrile</strong> (1.00 g, 7.29 mmol) in toluene (60.0 mL at -78 C. was added 1.0 M diisobutylaluminum hydride in toluene (18.2 mL, 18.2 mmol). The resulting mixture was stirred at -78 C. for 1 hour and allowed to warm to room temperature overnight. The 1:1 mixture of methanol and water (10 mL) was added and stirred for 35 minutes. The solid was filtered and washed with ethyl acetate. The filtrates were washed with water and brine then dried over Na2SO4, filtered, and concentrated. The crude product was purified with silica gel column (eluted with 10-50% ethyl acetate/hexanes) to give the desired product (0.77 g, 75%). 1H NMR (DMSO-d6) delta 10.49 (s, 1H), 9.88 (s, 1H), 7.10 (m, 2H), 6.87 (d, 1H).
  • 6
  • [ 473923-95-4 ]
  • [ 1377323-72-2 ]
  • 7
  • [ 473923-95-4 ]
  • [ 1377323-80-2 ]
  • 8
  • [ 473923-95-4 ]
  • 4-(3-fluoro-4-hydroxypiperidin-1-yl)-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2-3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanenitrile [ No CAS ]
  • 3-[(1-{3-cyano-2-[4-(7-[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-l-yl]propyl}-3-fluoropiperidin-4-yl)oxy]-5-fluorobenzonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
With di-tert-butyl-diazodicarboxylate; triphenylphosphine; In dichloromethane; at 20℃; for 6.25h; Step 10. 3-[(l-{3-Cyano-2-[4-(7-[2-(trimethylsilyl)ethoxy]methyl}-7H- pyrrolo[2,3-d]pyrimidin-4-yl)-lH-pyrazol-l-yl]propyl}-3-fluoropiperidin-4-yl)oxy]-5- fluorobenzonitrileTo a mixture of resin of triphenylphosphine (63.8 mg, 0.133 mmol) and 3-fluoro- 5-hydroxybenzonitrile (12.5 mg, 0.0910 mmol) in methylene chloride (0.6 mL) was added di-fert-butyl azodicarboxylate (22.3 mg, 0.0970 mmol) (DBAD). The mixture was stirred for 15 minutes before adding a solution of 4-(3-fluoro-4-hydroxypiperidin-l-yl)-3- [4-(7-[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-lH-pyrazol- l-yl]butanenitrile (30.3 mg, 0.0606 mmol) (diastereomer 2) in methylene chloride (0.2 mL). The reaction was stirred overnight at room temperature then another portion of resin of triphenylphosphine and DBAD was added and the solution was stirred for 6 hours, then the solvent was evaporated. The vial and resin were washed with DCM and filtered. The filtrates were washed with 10% aq. NaOH. The organic was dried over MgS04, filtered, and concentrated. The crude was diluted with methanol and purified with preparative LCMS (Sunfire C18 column eluting with a gradient MeCN/H20 containing 0.1% TFA at 30 mL/min) to give the desired product (11 mg, 29%). The product was synthesized from diastereomer 1 using same procedure in 14% yield. LCMS (M+H)+: 619.3.
  • 9
  • [ 473923-95-4 ]
  • [ 75-03-6 ]
  • [ 1404561-01-8 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 0.333333h;Microwave irradiation; Step 1: 3-Ethoxy-5-fluorobenzonitrile A mixture of <strong>[473923-95-4]3-fluoro-5-hydroxybenzonitrile</strong> (3.54 mmol, 0.5 g), potassium carbonate (6.01 mmol, 0.831 g), iodoethane (5.31 mmol, 0.844 g) and N,N-dimethyl formamide (4 ml) was heated 80 C for 20 minutes using a microwave reactor. The solvent was evaporated. Water was added and the resulting mixture was extracted three times with dichloromethane. The organic phases were separated and evaporated. The residue was dried with vacuum at 40 C. 0.544 g of the title compound was obtained. 1H NMR (400 MHz, CDCl3) delta ppm 1.44 (t, 3 H), 4.05 (q, 2 H), 6.81 - 6.87 (m, 1 H), 6.91 - 6.98 (m, 2 H).
With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 0.333333h;Microwave irradiation; Intermediate 13: (3-Ethoxy-5-fluorophenyl)methanamineStep 1: 3-Ethoxy-5-fluorobenzonitrile A mixture of <strong>[473923-95-4]3-fluoro-5-hydroxybenzonitrile</strong> (3.54 mmol, 0.5 g), potassium carbonate (6.01 mmol, 0.831 g), iodoethane (5.31 mmol, 0.844 g) and Nu,Nu-dimethyl formamide (4 ml) was heated 80 C for 20 minutes using a microwave reactor. The solvent was evaporated. Water was added and the resulting mixture was extracted three times with dichloromethane. The organic phases were separated and evaporated. The residue was dried with vacuum at 40 C. 0.544 g of the title compound was obtained. NMR (400 MHz, CDC13) delta ppm 1.44 (t, 3 H), 4.05 (q, 2 H), 6.81 - 6.87 (m, 1 H), 6.91 - 6.98 (m, 2 H).
  • 10
  • [ 473923-95-4 ]
  • 4’-fluoro-7’-(fluoromethylsulfonyl)spiro[1,3-dioxolane-2,1‘-indane] [ No CAS ]
  • 3-fluoro-5-[7’-(fluoromethylsulfonyl)spiro[1,3-dioxolane-2,1’-indane]-4’-yl]oxy-benzonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
48% With sodium hydrogencarbonate; In N,N-dimethyl-formamide; at 110℃; A solution of sodium hydrogen carbonate (108.5 mg, 1.29 mmol), <strong>[473923-95-4]3-fluoro-5-hydroxy-benzonitrile</strong> (85.0 mg, 0.62 mmol), and 4'-fluoro-7'- (fluoromethylsulfonyl)spiro[l,3-dioxolane-2, l'-indane] (150 mg, 0.52 mmol) in DMF (3 mL) in a vial were heated at 1 10 C overnight. The reaction mixture was partitioned between EtOAc and dilute NaOH. The EtOAc was washed with water, brine, dried over MgS04, filtered, and evaporated. The residue was chromatographed on a Biotage 25 g SNAP column with a 10% to 60% EtOAc:hexane gradient to give 3-fluoro-5-[7'- (fluoromethylsulfonyl)spiro[l ,3-dioxolane-2,r-indane]-4'-yl]oxy-benzonitrile (101 mg, 0.25 mmol, 48% yield) as a colorless glass.
48% With sodium hydrogencarbonate; In N,N-dimethyl-formamide; at 110℃; A solution of sodium hydrogen carbonate (108.5 mg, 1.29 mmol), 3 -fluoro-5 -hydroxy -benzonitrile (85.0 mg, 0.62 mmol), and 4'-fluoro-7'- (fluoromethylsulfonyl)spiro[l,3-dioxolane-2, l'-indane] (150 mg, 0.52 mmol) in DMF (3 mL) in a vial were heated at 1 10 C overnight. The reaction mixture was partitioned between EtOAc and dilute NaOH. The EtOAc was washed with water, brine, dried over MgS04, filtered, and evaporated. The residue was chromatographed on a Biotage 25 g SNAP column with a 10% to 60% EtOAc:hexane gradient to give 3-fluoro-5-[7'- (fluoromethylsulfonyl)spiro[l,3-dioxolane-2, r-indane]-4'-yl]oxy-benzonitrile (101 mg, 0.25 mmol, 48% yield) as a colorless glass.
  • 11
  • [ 473923-95-4 ]
  • N-((7-fluoro-3-oxo-2,3-dihydro-1H-inden-4-yl)(methyl)(oxo)-λ6-sulfanylidene)cyanamide [ No CAS ]
  • N-((7-(3-cyano-5-fluorophenoxy)-3-oxo-2,3-dihydro-1H-inden-4-yl)(methyl)(oxo)-λ6-sulfanylidene)cyanamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
3% With sodium hydrogencarbonate; In N,N-dimethyl-formamide; at 70℃;Sealed tube; Sodium hydrogen carbonate (60 mg, 0.71 mmol) was added to a vial containing a solution of <strong>[473923-95-4]3-fluoro-5-hydroxy-benzonitrile</strong> (65 mg, 0.48 mmol) and N-((7-fluoro-3-oxo-2,3-dih dro-lH-inden-4-yl)(methyl)(oxo)-lambda6- sulfanylidene)cyanamide (60 mg, 0.48 mmol) in DMF (1.5 mL). The sealed vial was heated at 70 C overnight. The reaction mixture was partitioned between EtOAc and dilute NaCl. The EtOAc was washed with water, brine, dried over MgS04, filtered, and evaporated. The residue was chromatographed on a Biotage 10 g SNAP column with a 30% to 100% EtOAcrhexane gradient to give the desired product (3.0 mg; 0.008 mmol; 3% yield), m/z (LCMS ESI-pos) [Mu+Eta] = 370
  • 12
  • [ 473923-95-4 ]
  • 2-bromo-1-fluoro-4-((trifluoromethyl)sulfonyl)benzene [ No CAS ]
  • 3-(2-bromo-4-((trifluoromethyl)sulfonyl)phenoxy)-5-fluorobenzonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
91% With caesium carbonate; In 1-methyl-pyrrolidin-2-one; at 50℃; for 1.5h; Cesium carbonate (46.0 mg, 0.14 mmol) was added all at once to 2- bromo- l -fluoro-4-((trifluoromethyl)sulfony])benzene (40.0 mg, 0.13 mmol) and 3-fluoro-5- hydroxybenzonitrile (20.0 mg, 0.14 mmol) in NMP (0.5 mL) and then warmed to 50 C and stirred for 1 .5 hours. The reaction mixture was cooled to room temperature and purified directly on reverse phase silica gel (12+M, 14 CV, 30-100% MeCN/water) affording Compound 118 (50 mg, 0.12 mmol, 91 % yield) as a white solid. LCMS ESI (-) m/z 422 (M- H).
  • 13
  • [ 473923-95-4 ]
  • 2-bromo-4-((difluoromethyl)sulfonyl)-1-fluorobenzene [ No CAS ]
  • 3-(2-bromo-4-((difluoromethyl)sulfonyl)phenoxy)-5-fluorobenzonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
88% With caesium carbonate; In 1-methyl-pyrrolidin-2-one; at 50℃; for 2.5h; Cesium carbonate (76.0 mg, 0.23 mmol) was added all at once to 2-bromo-4-((difluoromethyl)sulfonyl)-l -fluorobenzene (61.0 mg, 0.21 mmol) and <strong>[473923-95-4]3-fluoro-5-hydroxybenzonitrile</strong> (32.0 mg, 0.23 mmol) in NMP (0.5 mL) then warmed to 50 C and stirred for 2.5 hours. The mixture was cooled to room temperature and purified directly on reverse phase silica gel (12+M, 14 CV, 20-100% MeCN/water) affording Compound 132 (76 mg, 0.19 mmol, 88% yield) as a white solid. LCMS ESI (-) m/z 404 (M- H); 'HNMR (400 MHz, CDC13): delta 8.30 (d, 1 H), 7.95-7.93 (m, 1 H), 7.27-7.25 (m, 1 H), 7.15-7.13 (m, 2 H), 7.06-7.03 (m, 1 H), 6.24 (t, 1 H).
  • 14
  • [ 473923-95-4 ]
  • 5-((difluoromethyl)sulfonyl)-2-fluorobenzonitrile [ No CAS ]
  • 2-(3-cyano-5-fluorophenoxy)-5-((difluoromethyl)sulfonyl)benzonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% With caesium carbonate; In 1-methyl-pyrrolidin-2-one; at 50℃; for 1.5h; Cesium carbonate (70.0 mg, 0.22 mmol) was added all at once to 2-bromo-4-((difluoromethyl)sulfonyl)-l -fluorobenzene (46.0 mg, 0.20 mmol) and 5-((difluoromethyl)sulfonyl)-2-fluorobenzonitrile (30.0 mg, 0.22 mmol) in NMP (0.5 mL) then warmed to 50 C and stirred for 1.5 hours. The mixture was cooled to room temperature and purified directly on reverse phase silica gel (12+M, 14 CV, 20-100% MeCN/water) affording Compound 134 (44.8 mg, 0.13 mmol, 65% yield) as a white solid. LCMS ESI (-) m/z 351 (M-H). 1HNMR (400 MHz, CDC13): delta 8.34 (d, 1 H), 8.15-8.12 (m, 1 H), 7.40-7.37 (m, 1 H), 7.31-7.29 (m, 1 H), 7.22-7.19 (m, 1 H), 7.10 (d, 1 H), 6.26 (t, 1 H).
  • 15
  • [ 473923-95-4 ]
  • 4-(difluoromethylsulfonyl)-1-fluoro-2-methyl-benzene [ No CAS ]
  • 3-[4-(difluoromethylsulfonyl)-2-methyl-phenoxy]-5-fluoro-benzonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
34% With caesium carbonate; In 1-methyl-pyrrolidin-2-one; at 50℃;Sealed tube; Cesium carbonate (8- mg, 0.25 mmol) was added all at once to 4- (difluoromethylsulfonyl)-l-fluoro-2-methyl-benzene (50 mg, 0.22 mmol) and 3-fluoro-5- hydroxy-benzonitrile (34 mg, 0.25 mmol) in l-methyl-2-pyrrolidone (1.0 mL) at room temperature then the reaction vial was sealed with a threaded cap. The reaction mixture was then warmed to 50 C and continued to stir at this temperature until completion as judged by LC-MS. The mixture was cooled to room temperature then purified directly on reverse phase column (25+M, 14 CV, 20-100% MeCN/water) affording Compound 136 (27 mg, 0.08 mmol, 34% yield) as a white solid. LCMS ESI (-) m/z 340 (M-H). 'HNMR (400 MHz, CDC13): delta 7.93 (d, 1 H), 7.85-7.82 (m, 1 H), 7.23-7.20 (m, 1H), 7.11-7.09 (m, 1 H), 7.04 (d, 1 H), 7.03-6.98 (m, 1 H), 6.21 (t, 1 H), 2.39 (s, 3 H).
  • 16
  • [ 473923-95-4 ]
  • 1,3-dibromo-2-methyl-4-(trifluoromethylsulfonyl)benzene [ No CAS ]
  • 3-[3-bromo-2-methyl-4-(trifluoromethylsulfonyl)phenoxy]-5-fluoro-benzonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
59% With caesium carbonate; In 1-methyl-pyrrolidin-2-one; at 50℃; for 20.0h;Sealed tube; Cesium carbonate (51.2 mg, 0.16 mmol) was added all at once to l ,3-dibromo-2-methyl-4-(trifluoromethylsulfonyl)benzene (100.0 mg, 0.26 mmol) and <strong>[473923-95-4]3-fluoro-5-hydroxy-benzonitrile</strong> (35.9 mg, 0.26 mmol) in l-methyl-2-pyrrolidone (1.0 mL) at room temperature then the reaction vial was sealed with a threaded cap. The reaction mixture was then warmed to 50 C and continued to stir at this temperature until completion as judged by LC-MS (20 hours). The mixture was cooled to room temperature then purified directly on reverse phase column (25+M, 14 CV, 20-100% MeCN/water) affording Compound 141 (71 mg, 0.15 mmol, 59% yield) as a colorless oil. LCMS ESI (+) m/z 438 (M+H).
  • 17
  • [ 473923-95-4 ]
  • 7’-(difluoromethylsulfonyl)-4’-fluoro-spiro[1,3-dioxolane-2,1’-indane] [ No CAS ]
  • 3-((7-((difluoromethyl)sulfonyl)-2,3-dihydrospiro[indene-1,2’-[1,3]dioxolan]-4-yl)oxy)-5-fluorobenzonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
69% With cesium bicarbonate; In 1-methyl-pyrrolidin-2-one; at 110℃; for 1.08333h;Inert atmosphere; Microwave irradiation; A mixture of 3- fluoro-5-hydroxy-benzonitrile (1.33 g, 9.7 mmol), 7'-(difluoromethylsulfonyl)-4'-fluoro- spiro[l ,3-dioxolane-2,l '-indane] (1.0 g, 3.24 mmol), and cesium bicarbonate (1.26 g, 6.5 mmol) in l -methyl-2-pyrrolidone (1.8 mL) was heated under N2 at 1 10 C (microwave) for 1 hour and 5 minutes. The reaction was repeated ten times. The reaction mixtures were combined, diluted with EtOAc, and washed twice with 1 N NaOH. The combined aqueous layer was extracted with EtOAc. The EtOAc extracts were combined and washed with brine, dried over Na2S04, filtered, and concentrated to about 100 mL to give a suspension. The suspension was filtered to give 3-((7-((difluoromethyl)sulfonyl)-2,3-dihydrospiro[indene- l ,2'-[l ,3]dioxolan]-4-yl)oxy)-5-fluorobenzonitrile as an off-white solid (6.25 g). The filtrate was diluted with EtOAc, washed with brine (3X), dried over Na2S04, filtered, and concentrated. The residue was purified by flash column chromatography on silica gel with EtOAc/hexane (0% to 40%) to give additional 3-((7-((difluoromethyl)sulfonyl)-2,2-difluoro- 2,3-dihydrospiro[indene-l ,2'-[l,3]dioxolan]-4-yl)oxy)-5-fluorobenzonitrile (3.3 g, 69% combined yield) as a white solid. LCMS ESI (+) m/z 426 (M+H).
69% With cesium bicarbonate; In 1-methyl-pyrrolidin-2-one; at 110℃; for 1.08h;Inert atmosphere; Microwave irradiation; A mixture of 3- fluoro-5 -hydroxy -benzonitrile (1.33 g, 9.7 mmol), 7'-(difluoromethylsulfonyl)-4'-fluoro- spiro[l,3-dioxolane-2, l'-indane] (1.0 g, 3.24 mmol), and cesium bicarbonate (1.26 g, 6.5 mmol) in l-methyl-2-pyrrolidone (1.8 mL) was heated under N2 at 1 10 C (microwave) for 1 hour and 5 minutes. The reaction was repeated ten times. The reaction mixtures were combined, diluted with EtOAc, and washed twice with 1 N NaOH. The combined aqueous layer was extracted with EtOAc. The EtOAc extracts were combined and washed with brine, dried over Na2S04, filtered, and concentrated to about 100 mL to give a suspension. The suspension was filtered to give 3-((7-((difluoromethyl)sulfonyl)-2,3-dihydrospiro[indene- l,2'-[l,3]dioxolan]-4-yl)oxy)-5-fluorobenzonitrile as an off-white solid (6.25 g). The filtrate was diluted with EtOAc, washed with brine (3X), dried over Na2S04, filtered, and concentrated. The residue was purified by flash column chromatography on silica gel with EtOAc/hexane (0% to 40%) to give additional 3-((7-((difluoromethyl)sulfonyl)-2,2-difluoro- 2,3-dihydrospiro[indene-l,2'-[l,3]dioxolan]-4-yl)oxy)-5-fluorobenzonitrile (3.3 g, 69% combined yield) as a white solid. LCMS ESI (+) m/z 426 (M+H).
69% With caesium carbonate; In 1-methyl-pyrrolidin-2-one; at 110℃; for 1.08333h;Inert atmosphere; Microwave irradiation; [00497] Step A: Preparation of 3-((7-((difluoromethyl)sulfonyl)-2,3-dihydrospirorindene- L2'-rL31dioxolan1-4-yl)oxy)-5-fluorobenzonitrile: A mixture of 3-fiuoro-5-hydroxy- benzonitrile (1.33 g, 9.7 mmol), 7'-(difluoromethylsulfonyl)-4'-fluoro-spiro[l,3-dioxolane- 2, l'-indane] (1.0 g, 3.24 mmol), and cesium bicarbonate (1.26 g, 6.5 mmol) in l-methyl-2- pyrrolidone (1.8 mL) was heated under N2 at 110 C (microwave) for 1 hour and 5 minutes. The reaction was repeated ten times. The reaction mixtures were combined, diluted with EtOAc, and washed twice with 1 N NaOH. The combined aqueous layer was extracted with EtOAc. The EtOAc extracts were combined and washed with brine, dried over Na2S04, filtered, and concentrated to about 100 mL to give a suspension. The suspension was filtered to give 3-((7-((difluoromethyl)sulfonyl)-2,3-dihydrospiro[indene-l,2'-[l,3]dioxolan]-4- yl)oxy)-5-fluorobenzonitrile as an off-white solid (6.25 g). The filtrate was diluted with EtOAc, washed with brine (3X), dried over Na2S04, filtered, and concentrated. The residue was purified by flash column chromatography on silica gel with EtOAc/hexane (0% to 40%) to give additional 3-((7-((difluoromethyl)sulfonyl)-2,2-difluoro-2,3-dihydrospiro[indene-l,2'- [l,3]dioxolan]-4-yl)oxy)-5-fluorobenzonitrile (3.3 g, 69% combined yield) as a white solid. LCMS ESI (+) m/z 426 (M+H).
69% With cesium bicarbonate; In 1-methyl-pyrrolidin-2-one; at 110℃; for 1.08333h;Inert atmosphere; Microwave irradiation; A mixture of <strong>[473923-95-4]3-fluoro-5-hydroxy-benzonitrile</strong> (1.33 g, 9.7 mmol), 7'-(difluoromethylsulfonyl)-4'-fluoro-spiro[l,3-dioxolane-2, -indane] (1.0 g, 3.24 mmol), and cesium bicarbonate (1.26 g, 6.5 mmol) in 1-m ethyl -2-pyrrolidone (1.8 mL) was heated under N2 at 110 C (microwave) for 1 hour and 5 minutes. The reaction was repeated ten times. The reaction mixtures were combined, diluted with EtOAc, and washed twice with 1 N NaOH. The combined aqueous layer was extracted with EtOAc. The EtOAc extracts were combined and washed with brine, dried over Na2S04, filtered, and concentrated to about 100 mL to give a suspension. The suspension was filtered to give 3-((7-((difluoromethyl)sulfonyl)-2,3- dihydrospiro[indene-l,2'-[l,3]dioxolan]-4-yl)oxy)-5-fluorobenzonitrile as an off-white solid (6.25 g). The filtrate was diluted with EtOAc, washed with brine (3X), dried over Na2S04, filtered, and concentrated. The residue was purified by flash column chromatography on silica gel with EtOAc/hexane (0% to 40%) to give additional 3-((7-((difluoromethyl)sulfonyl)-2,2- difluoro-2,3-dihydrospiro[indene-1,2'-[l,3]dioxolan]-4-yl)oxy)-5-fluorobenzonitrile (3.3 g, 69% combined yield) as a white solid. LCMS ESI (+) m/z 426 (M+H).
69% With cesium bicarbonate; In 1-methyl-pyrrolidin-2-one; at 110℃;Inert atmosphere; Microwave irradiation; A mixture of <strong>[473923-95-4]3-fluoro-5-hydroxy-benzonitrile</strong> (1.33 g, 9.7 mmol), 7'-(difluoromethylsulfonyl)-4'-fluoro-spiro[1,3-dioxolane-2,1'-indane] (1.0 g, 3.24 mmol), and cesium bicarbonate (1.26 g, 6.5 mmol) in 1-methyl-2-pyrrolidone (1.8 mL) was heated under N2 at 110 C. (microwave) for 1 hour and 5 minutes. The reaction was repeated ten times. The reaction mixtures were combined, diluted with EtOAc, and washed twice with 1 N NaOH. The combined aqueous layer was extracted with EtOAc. The EtOAc extracts were combined and washed with brine, dried over Na2SO4, filtered, and concentrated to about 100 mL to give a suspension. The suspension was filtered to give 3-((7-((difluoromethyl)sulfonyl)-2,3-dihydrospiro[indene-1,2'-[1,3]dioxolan]-4-yl)oxy)-5-fluorobenzonitrile as an off-white solid (6.25 g). The filtrate was diluted with EtOAc, washed with brine (3*), dried over Na2SO4, filtered, and concentrated. The residue was purified by flash column chromatography on silica gel with EtOAc/hexane (0% to 40%) to give additional 3-((7-((difluoromethyl)sulfonyl)-2,2-difluoro-2,3-dihydrospiro[indene-1,2'-[1,3]dioxolan]-4-yl)oxy)-5-fluorobenzonitrile (3.3 g, 69% combined yield) as a white solid. LCMS ESI (+) m/z 426 (M+H).
With caesium carbonate; In 1-methyl-pyrrolidin-2-one; at 110℃; for 1.08333h;Microwave irradiation; Inert atmosphere; A mixture of 3- fluoro-5-hydroxy-benzonitrile (1.33 g, 9.7 mmol), 7'-(difluoromethylsulfonyl)-4'-fluoro- spiro[l,3-dioxolane-2,l'-indane] (1.0 g, 3.24 mmol), and cesium bicarbonate (1.26 g, 6.5 mmol) in l-methyl-2-pyrrolidone (1.8 mL) was heated under N2 at 110 C (microwave) for 1 hour and 5 minutes. The reaction was repeated ten times. The reaction mixtures were combined, diluted with EtOAc, and washed twice with 1 N NaOH. The combined aqueous layer was extracted with EtOAc. The EtOAc extracts were combined and washed with brine, dried over Na2S04, filtered, and concentrated to about 100 mL to give a suspension. The suspension was filtered to give 3-((7-((difluoromethyl)sulfonyl)-2,3-dihydrospiro[indene- l,2'-[l,3]dioxolan]-4-yl)oxy)-5-fluorobenzonitrile as an off-white solid (6.25 g). The filtrate was diluted with EtOAc, washed with brine (3X), dried over Na2S04, filtered, and (0766) concentrated. The residue was purified by flash column chromatography on silica gel with EtOAc/hexane (0% to 40%) to give additional 3-((7-((difluoromethyl)sulfonyl)-2,2-difluoro- (0767) 2.3-dihydrospiro[indene-l,2'-[l,3]dioxolan]-4-yl)oxy)-5-fluorobenzonitrile (3.3 g, 69% combined yield) as a white solid. LCMS ESI (+) m/z 426 (M+H).

  • 18
  • [ 473923-95-4 ]
  • 1,3-dichloro-2-methyl-4-(trifluoromethylsulfonyl)benzene [ No CAS ]
  • 3-fluoro-5-[3-chloro-2-methyl-4-(trifluoromethylsulfonyl)phenoxy]benzonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
36% With caesium carbonate; In 1-methyl-pyrrolidin-2-one; at 20 - 50℃; for 2.75h; Cesium carbonate (71 mg, 0.22 mmol) was added all at once to a solution of 1 ,3-dichloro-2-methyl-4- (trifluoromethylsulfonyl)benzene (70 mg, 0.24 mmol) and <strong>[473923-95-4]3-fluoro-5-hydroxy-benzonitrile</strong> (30 mg, 0.22 mmol) in l-methyl-2-pyrrolidone (1 mL) at room temperature and stirred for 45 minutes, warmed to 50 C and stirred for 2 hours. The mixture was cooled to room temperature and purified directly on reverse phase column (25+M, 14 CV, 30-100% MeCN/water) affording a slightly impure product which was further purified on silica gel (10 g SNAP, 14 CV, 2-26% EtOAc hexane) affording Compound 144 (33 mg, 0.08 mmol, 36% yield) as a white solid. LCMS ESI (-) m/z 392 (M-H); 'HNMR (400 MHz, CDC13): delta 8.05 (m, 1 H), 7.29-7.26 (m, 1 H), 7.14 (s, 1 H), 7.05-7.02 (m, 1 H), 6.94-6.91 (m, 1 H), 2.46 (s, 3 H).
  • 19
  • [ 473923-95-4 ]
  • 2,6-dichloro-3-methylsulfonyl-benzonitrile [ No CAS ]
  • 2-chloro-6-(3-cyano-5-fluorophenoxy)-3-(methylsulfonyl)benzonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
51% With caesium carbonate; In 1-methyl-pyrrolidin-2-one; at 0 - 50℃; for 18.0h; A solution of 3-fuoro-5-hydroxy- benzonitrile (27.41 mg, 0.2 mmol) in 1 -methyl-2-pyrrolidone (0.5 mL) was added dropwise to an ice cold mixture of 2,6-dichloro-3-methylsulfonyl-benzonitrile (50.0 mg, 0.2 mmol) and cesium carbonate (39 mg, 0.12 mmol) in l -methyl-2-pyrrolidone (0.5 mL). The reaction mixture was stirred at 0 C for two hours then warmed to 50 C for 16 hours. The reaction mixture was cooled to room temperature then directly purified on reverse phase silica gel (25+M, 14 CV, 20-100% MeCN/water) affording Compound 152 (38 mg, 0.1 mmol, 51 % yield) as a white solid. LCMS ESI (-) m/z 349 (M-H); 'HNMR (400 MHz, CDC13): delta 8.32 (d, 1 H), 7.38-7.35 (m, 1 H), 7.26-7.25 (m, 1 H), 7.18-7.15 (m, 1 H), 6.97 (d, 1 H), 3.30 (s, 3 H).
  • 20
  • [ 473923-95-4 ]
  • 4’-fluoro-7’-methylsulfonyl-spiro[1,3-dioxolane-2,1’-indane] [ No CAS ]
  • 3-fluoro-5-(7’-methylsulfonylspiro[1,3-dioxolane-2,1’-indane]-4’-yl)oxy-benzonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
24% With cesium bicarbonate; In 1-methyl-pyrrolidin-2-one; at 160℃; for 2.5h;Microwave irradiation; Sealed tube; Inert atmosphere; Cesium hydrogen carbonate (320.48 mg, 1 .65mmol) was added all at once to 4'-fluoro-7'-methylsulfonyl- spiro[l ,3-dioxolane-2,l '-indane] (300 mg, 1.1 mmol) and <strong>[473923-95-4]3-fluoro-5-hydroxy-benzonitrile</strong> (227 mg, 1.65 mmol) in l -methyl-2-pyrrolidone (4.4 mL) at room temperature in a microwave reaction vial equipped with a stir bar, flushed with nitrogen then sealed with a crimp cap. The reaction mixture was heated to 160 C for 2 hours in a microwave reactor. Additional CsHC03 (100 mg) was added and the mixture was heated at 160 C for 30 minutes in a microwave reactor. The mixture was purified directly on reverse phase column (25+M, 14 CV, 20-100% MeCN/water) affording 3-fluoro-5-(7'-methylsulfonylspiro[l ,3- dioxolane-2,r-indane]-4'-yl)oxy-benzonitrile (104 mg, 0.26 mmol, 24% yield).
24% With cesium bicarbonate; In 1-methyl-pyrrolidin-2-one; at 20 - 160℃; for 2.5h;Microwave irradiation; Sealed tube; Inert atmosphere; Alternative protocol for the synthesis of 3-fluoro-5-(7'- methylsulfonylspiro[l,3-dioxolane-2,r-indane]-4'-yl)oxy-benzonitrile: Cesium hydrogen carbonate (320.48 mg, 1.65mmol) was added all at once to 4'-fluoro-7'-methylsulfonyl- spiro[l,3-dioxolane-2, l'-indane] (300 mg, 1.1 mmol) and 3 -fluoro-5 -hydroxy -benzonitrile (227 mg, 1.65 mmol) in l-methyl-2-pyrrolidone (4.4 mL) at room temperature in a microwave reaction vial equipped with a stir bar, flushed with nitrogen then sealed with a crimp cap. The reaction mixture was heated to 160 C for 2 hours in a microwave reactor. Additional CsHC03 (100 mg) was added and the mixture was heated at 160 C for 30 minutes in a microwave reactor. The mixture was purified directly on reverse phase column (25+M, 14 CV, 20-100% MeCN/water) affording 3-fluoro-5-(7'-methylsulfonylspiro[l,3- dioxolane-2, l'-indane]-4'-yl)oxy-benzonitrile (104 mg, 0.26 mmol, 24% yield).
  • 21
  • [ 473923-95-4 ]
  • N-((7-fluoro-3-hydroxy-2,3-dihydro-1H-inden-4-yl)(methyl)(oxo)-λ6-sulfanylidene)cyanamide [ No CAS ]
  • N-((7-(3-cyano-5-fluorophenoxy)-3-hydroxy-2,3-dihydro-1H-inden-4-yl)(methyl)(oxo)-λ6-sulfanylidene)cyanamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
69% With sodium hydrogencarbonate; In N,N-dimethyl-formamide; at 100℃; for 168.0h;Sealed tube; Sodium hydrogen carbonate (79.3 mg, 0.94 mmol) was added to a solution of <strong>[473923-95-4]3-fluoro-5-hydroxy-benzonitrile</strong> (86.27mg, 0.63 mmol) and N-((7-fluoro-3-hydroxy-2,3-dihydro-lH-inden-4-yl)(methyl)(oxo)- 6- sulfanylidene)cyanamide (80 mg, 0.31 mmol) (Example 189, Step C) in DMF (3 mL). The vial was sealed and heated at 100 C over a weekend. The reaction mixture was partitioned between EtOAc and dilute aqueous NaOH. The EtOAc was washed with water, two portions of brine, dried over MgS04, filtered, and evaporated. The residue was chromatographed on a Biotage 25M reverse phase column with a 20 % to 90 % ACN:water gradient to afford N-((7- (3-cyano-5-fluoGammaophenoxy)-3-hydroxy-2,3-dihydro-lH-inden-4-yl)(methyl)(oxo)-lambda6- sulfanylidene)cyanamide (80 mg, 0.21 mmol, 69% yield), m/z (ES-API-pos ) [Mu+Eta] = 372.
69% With sodium hydrogencarbonate; In N,N-dimethyl-formamide; at 100℃;Sealed tube; Sodium hydrogen carbonate (79.3 mg, 0.94 mmol) was added to a solution of <strong>[473923-95-4]3-fluoro-5-hydroxy-benzonitrile</strong> (86.27mg, 0.63 mmol) and N-((7-fluoro-3-hydroxy-2,3-dihydro-lH-inden-4-yl)(methyl)(oxo)- 6- sulfanylidene)cyanamide (80 mg, 0.31 mmol) (Example 189, Step C) in DMF (3 mL). The vial was sealed and heated at 100 C over a weekend. The reaction mixture was partitioned between EtOAc and dilute aqueous NaOH. The EtOAc was washed with water, two portions of brine, dried over MgS04, filtered, and evaporated. The residue was chromatographed on a Biotage 25M reverse phase column with a 20 % to 90 % ACN:water gradient to afford N-((7- (3-cyano-5-fluorophenoxy)-3-hydroxy-2,3-dihydro-lH-inden-4-yl)(methyl)(oxo)^6- sulfanylidene)cyanamide (80 mg, 0.21 mmol, 69% yield), m/z (ES-API-pos ) [Mu+Eta] = 372
69% With sodium hydrogencarbonate; In N,N-dimethyl-formamide; at 100℃; for 168.0h;Sealed tube; N-((7-(3 -cyano-5 -fluorophenoxy)-3 -hydroxy-2.3 -dihydro- lH-inden-4- yl)(methvD(oxo)-lambda6-sulfanylidene)cvanamide: Sodium hydrogen carbonate (79.3 mg, 0.94 mmol) was added to a solution of <strong>[473923-95-4]3-fluoro-5-hydroxy-benzonitrile</strong> (86.27mg, 0.63 mmol) and N-((7- fluoro-3-hydroxy-2,3-dihydro-lH-inden-4-yl)(methyl)(oxo)-lambda6-sulfanylidene)cyanamide (80 mg, 0.31 mmol) in DMF (3 mL). The vial was sealed and heated at 100 C over a weekend. The reaction mixture was partitioned between EtOAc and dilute aqueous NaOH. The EtOAc was washed with water, two portions of brine, dried over MgS04, filtered, and evaporated. The residue was chromatographed on a Biotage 25M reverse phase column with a 20 % to 90 % ACN:water gradient to afford N-((7-(3-cyano-5-fluorophenoxy)-3-hydroxy-2,3-dihydro-lH- inden-4-yl)(methyl)(oxo)-lambda6-sulfanylidene)cyanamide (80 mg, 0.21 mmol, 69% yield), m/z (ES- API-pos ) [M+H] = 372.
69% With sodium hydrogencarbonate; In N,N-dimethyl-formamide; at 100℃;Sealed tube; Sodium hydrogen carbonate (79.3 mg, 0.94 mmol) was added to a solution of <strong>[473923-95-4]3-fluoro-5-hydroxy-benzonitrile</strong> (86.27 mg, 0.63 mmol) and N-((7-fluoro-3-hydroxy-2,3-dihydro-1H-inden-4-yl)(methyl)(oxo)-lambda6-sulfanylidene)cyanamide (80 mg, 0.31 mmol) in DMF (3 mL). The vial was sealed and heated at 100 C. over a weekend. The reaction mixture was partitioned between EtOAc and dilute aqueous NaOH. The EtOAc was washed with water, two portions of brine, dried over MgSO4, filtered, and evaporated. The residue was chromatographed on a Biotage 25M reverse phase column with a 20% to 90% ACN:water gradient to afford N-((7-(3-cyano-5-fluorophenoxy)-3-hydroxy-2,3-dihydro-1H-inden-4-yl)(methyl)(oxo)-lambda6-sulfanylidene)cyanamide (80 mg, 0.21 mmol, 69% yield). m/z (ES-API-pos) [M+H]=372.

  • 22
  • [ 473923-95-4 ]
  • 4-fluoro-7-(S-(trifluoromethyl)sulfonimidoyl)-2,3-dihydro-1H-inden-1-yl acetate [ No CAS ]
  • 3-fluoro-5-((1-hydroxy-7-(S-(trifluoromethyl)sulfonimidoyl)-2,3-dihydro-1H-inden-4-yl)oxy)benzonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
33% A solution of 4-fluoro-7-(5-(trifluoromethyl)sulfonimidoyl)-2,3-dihydro-lH-inden-l-yl acetate (9.0 mg, 0.028 mmol), <strong>[473923-95-4]3-fluoro-5-hydroxy-benzonitrile</strong> (3.8 mg, 0.028 mmol), and cesium bicarbonate (5.4 mg, 0.028 mmol) in DMF (0.5 mL) was stirred at 90 C for 3 hours. The reaction mixture was poured into 50 mL of water and extracted with 3 x 20 mL Et20. The combined organics were rinsed with 10 mL of brine, dried with MgS04, filtered, and concentrated to dryness. Purification was achieved by chromatography on silica using 5-25% EtOAc/hexane to afford an intermediate acetate derivative: LCMS ESI (+) (M+H) m/z 443. The product residue was dissolved in 0.5 mL of acetonitrile and treated with 1.0 mL of 22.5% HC1 in water. The reaction mixture was left to stir overnight. Volatiles were removed by concentration under reduced pressure. The reaction mixture was poured into 10 mL of water and extracted with 3 x 10 mL EtOAc. The combined organics were rinsed with 10 mL of brine, dried with MgS04, filtered, and concentrated to dryness. Purification was achieved by chromatography on silica using 10-30% EtOAc/hexane to afford Compound 258 as a white solid (3.7 mg, 33%). LCMS ESI (-) (M-H) m/z 399; NMR (400 MHz, CDC13): delta 7.96 (d, 1H), 7.27-7.22 (m, 1H), 7.18-7.15 (m, 1H), 7.07-7.03 (m, 1 H), 6.97 (d, 1 H), 5.59 (d, 1 H), 4.59 (s, 1H), 3.89 (s, 1H), 3.18 (dt, 1H), 2.96 (ddd, 1H), 2.43-2.27 (m, 2H). Retention time = 5.55 min (long HPLC method).
  • 23
  • [ 473923-95-4 ]
  • 3-fluoro-5-((1-oxo-7-(S-(trifluoromethyl)sulfonimidoyl)-2,3-dihydro-1H-inden-4-yl)oxy)benzonitrile [ No CAS ]
  • 24
  • [ 473923-95-4 ]
  • 3-fluoro-5-((1-((3-methoxypropyl)imino)-7-(S-(trifluoromethyl)sulfonimidoyl)-2,3-dihydro-1H-inden-4-yl)oxy)benzonitrile [ No CAS ]
  • 25
  • [ 473923-95-4 ]
  • 3-((7-(N-allyl-S-(trifluoromethyl)sulfonimidoyl)-2,2-difluoro-1-oxo-2,3-dihydro-1H-inden-4-yl)oxy)-5-fluorobenzonitrile [ No CAS ]
  • 26
  • [ 473923-95-4 ]
  • (7-fluoro-3-hydroxy-2,3-dihydro-1H-inden-4-yl)(imino)(trifluoromethyl)-λ6-sulfanone [ No CAS ]
  • 3-fluoro-5-((1-hydroxy-7-(S-(trifluoromethyl)sulfonimidoyl)-2,3-dihydro-1H-inden-4-yl)oxy)benzonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
28% With cesium bicarbonate; In N,N-dimethyl-formamide; at 90℃; for 5.5h; A solution of (7-fluoro-3-hydroxy-2,3-dihydro-lH-inden-4-yl)(imino)(trifluoromethyl)- 6-sulfanone (428 mg, 1.5 mmol), <strong>[473923-95-4]3-fluoro-5-hydroxy-benzonitrile</strong> (207 mg, 1.5 mmol), and cesium bicarbonate (322 mg, 1.66 mmol) in DMF (6.0 mL) was stirred at 90 C for 4.5 hours. An additional 40 mg of cesium bicarbonate was added and the reaction mixture heated for an additional hour. The reaction mixture was poured into 60 mL of water and extracted with 3x20 mL Et20. The combined organics were rinsed with 20 mL of brine, dried with MgS04, filtered, and concentrated to dryness. Purification was achieved by chromatography on silica using 10-35% EtOAc/hexane to afford 3-fluoro-5-((l-hydroxy-7-(5-(trifluoromethyl)sulfonimidoyl)-2,3- dihydro-lH-inden-4-yl)oxy)benzonitrile (171 mg, 28%). LCMS ESI (+) (Mu+Eta) m/z 401.
  • 27
  • [ 473923-95-4 ]
  • [methyl-oxo-[1,2,2,7-tetrafluoro-3-oxo-indan-4-yl]-λ6-sulfanylidene]cyanamide [ No CAS ]
  • [[7-(3-cyano-5-fluoro-phenoxy)-1,2,2-trifluoro-3-oxoindan-4-yl]-methyl-oxo-λ6-sulfanylidene]cyanamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
37% With cesium bicarbonate; In N,N-dimethyl-formamide; at 20℃; for 0.416667h; Cesium bicarbonate (88.6 mg, 0.46 mmol) was added to a solution of <strong>[473923-95-4]3-fluoro-5-hydroxy-benzonitrile</strong> (40.7 mg, 0.3 mmol) and [methyl-oxo-[l ,2,2,7-tetrafluoro-3-oxo-indan-4-yl]-lambda6-sulfanylidene]cyanamide (70 mg, 0.23 mmol) in N,N-dimethylformamide (3 mL). The mixture was stirred at ambient temperature. After 25 minutes, the reaction mixture was partitioned between EtOAc and dilute aqueous NaCl. The EtOAc was washed with 2 portions of brine, dried over MgS04, filtered, and evaporated. The residue was chromatographed on a Biotage 10 g ultra SNAP column with a 20% to 80% EtOAc:hexane gradient to afford [[7-(3-cyano-5-fluoro-phenoxy)-l ,2,2-trifluoro-3-oxo- indan-4-yl]-methyl-oxo^6-sulfanylidene]cyanamide (35.5 mg, 0.084 mmol, 37% yield) as a diastereomeric mixture, m/z (ES-API-pos) [M+H+18] = 442.
37% With cesium bicarbonate; In N,N-dimethyl-formamide; at 20℃; Cesium bicarbonate (88.6 mg, 0.46 mmol) was added to a solution of <strong>[473923-95-4]3-fluoro-5-hydroxy-benzonitrile</strong> (40.7 mg, 0.3 mmol) and [methyl-oxo-[l,2,2,7-tetrafluoro-3-oxo-indan-4-yl]-lambda6-sulfanylidene]cyanamide (70 mg, 0.23 mmol) in N,N-dimethylformamide (3 mL). The mixture was stirred at ambient temperature. After 25 minutes, the reaction mixture was partitioned between EtOAc and dilute aqueous NaCl. The EtOAc was washed with 2 portions of brine, dried over MgSC^, filtered, and evaporated. (0668) The residue was chromatographed on a Biotage 10 g ultra SNAP column with a 20% to 80% EtOAc:hexane gradient to afford [[7-(3-cyano-5-fluoro-phenoxy)-l,2,2-trifluoro-3-oxo- indan-4-yl]-methyl-oxo^6-sulfanylidene]cyanamide (35.5 mg, 0.084 mmol, 37% yield) as a diastereomeric mixture, m/z (ES-API-pos) [M+H+18] = 442.
  • 28
  • [ 473923-95-4 ]
  • (1R)-1,2,2,7-tetrafluoro-3-oxo-indane-4-sulfonamide [ No CAS ]
  • (1R)-7-[(5-cyano-3-pyridyl)oxy]-1,2,2-trifluoro-3-oxo-indane-4-sulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
21% With cesium bicarbonate; In 1-methyl-pyrrolidin-2-one; at 60℃; for 1.0h; A mixture of ( l^)-l ,2,2,7-tetrafluoro-3-oxo-indane-4-sulfonamide (66 mg, 0.23 mmol), 3-cyano-5-hydroxypyridine (42 mg, 0.35 mmol) and cesium bicarbonate (59 mg, 0.3 mmol) in NMP (2.3 mL) was heated at 60 C for 1 hour. After cooling, the reaction mixture was partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc. The combined organic layers were washed with water and brine, dried and concentrated. The residue was purified by flash chromatography on silica gel (30-80% EtOAc/hexane) to give (lR)-7-[(5-cyano-3-pyridyl)oxy]-l ,2,2-trifluoro-3-oxo-indane-4- sulfonamide (19 mg, 21 %). LCMS ESI (-) m/z 382 (M-H).
  • 29
  • [ 473923-95-4 ]
  • (1R)-1,2,2,7-tetrafluoro-3-oxo-indane-4-sulfonamide [ No CAS ]
  • (1R)-1,2,2-trifluoro-7-[(5-fluoro-3-pyridyl)oxy]-3-oxo-indane-4-sulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
30% With cesium bicarbonate; In 1-methyl-pyrrolidin-2-one; at 60℃; for 8.0h; A mixture of (l/?)-l ,2,2,7-tetrafluoro-3-oxo-indane-4-sulfonamide (70 mg, 0.25 mmol), 3-fluoro-5-hydroxypyridine (42 mg, 0.37 mmol) and cesium bicarbonate (62 mg, 0.32 mmol) in NMP (1.2 mL) was heated at 60 C for 8 hours. After cooling, the reaction mixture was partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc. The combined organic layers were washed with water and brine, dried and concentrated. The residue was purified by flash chromatography on silica gel (30-70% EtOAc hexane) to give (l)-l ,2,2-trifluoro-7-[(5-fluoro-3-pyridyl)oxy]-3-oxo-indane-4- sulfonamide (28 mg, 30%). LCMS ESI (-) m/z 375 (M-H).
  • 30
  • [ 473923-95-4 ]
  • methyl 2-bromo-3-fluoro-6-(methylsulfonyl)benzoate [ No CAS ]
  • methyl 2-bromo-3-(3-cyano-5-fluorophenoxy)-6-(methylsulfonyl)benzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
100% With sodium hydrogencarbonate; In N,N-dimethyl-formamide; at 90℃; for 16.0h; Methyl 2-bromo-3 -fluoro-6-methylsulfonyl-benzoate (200 mg, 0.64 mmol) was combined with <strong>[473923-95-4]3-fluoro-5-hydroxy-benzonitrile</strong> (132 mg, 0.96 mmol) and I N-dimethylformamide (2.5 mL). The solution was treated in a single portion with sodium bicarbonate (108 mg, 1.3 mmol) and the reaction mixture was heated to 90 C for 16 hours. The reaction mixture was cooled, diluted with Et20 and water and then separated. The aqueous layer was washed with Et20, then the combined organics were washed with water, 10% K2CO3, saturated NaCl, dried over Na2SO4 and concentrated in vacuo to provide methyl2-bromo-3 -(3 -cyano-5 -fluorophenoxy)-6-(rnethylsulfonyl)benzoate as an orange oil (276 rng, quant.). 1F{NMR (400 IVII-{z, CDC13): 5 8.03 (d, 1H), 7.25-7.22 (m, 1H), 7.14 (d, 1H), 7.10- 7.09 (m, 1H), 7.03-7.00 (m, 1H), 4.04 (s, 3H), 3.20 (s, 3H).
100% With sodium hydrogencarbonate; In N,N-dimethyl-formamide; at 90℃; for 16.0h; Methyl 2-bromo-3-fluoro-6-methylsulfonyl-benzoate (200 mg, 0.64 mmol) was combined with <strong>[473923-95-4]3-fluoro-5-hydroxy-benzonitrile</strong> (132 mg, 0.96 mmol) and N, N-dimethylformamide (2.5 mL). The solution was treated in a single portion with sodium bicarbonate (108 mg, 1.3 mmol) and the reaction mixture was heated to 90 C for 16 hours. The reaction mixture was cooled, diluted with Et20 and water and then separated. The aqueous layer was washed with Et20, then the combined organics were washed with water, three times with 10% K2CO3, saturated NaCl, dried over Na2S04 and concentrated in vacuo to an orange oil to provide methyl 2-bromo-3-(3-cyano-5-fluorophenoxy)-6- (methylsulfonyl)benzoate (276 mg, quant.). NMR (400 MHz, CDC13): delta 8.03 (d, 1H), 7.25-7.22 (m, 1H), 7.14 (d, 1H), 7.10-7.09 (m, 1H), 7.03-7.00 (m, 1H), 4.04 (s, 3H), 3.20 (s, 3H).
100% With sodium hydrogencarbonate; In N,N-dimethyl-formamide; at 90℃; for 16.0h; Methyl 2-bromo-3-fluoro-6-methylsulfonyl-benzoate (200 mg, 0.64 mmol) was combined with <strong>[473923-95-4]3-fluoro-5-hydroxy-benzonitrile</strong> (132 mg, 0.96 mmol) and N,N-dimethylformamide (2.5 mL). The solution was treated in a single portion with sodium bicarbonate (108 mg, 1.3 mmol) and the reaction mixture was heated to 90 C. for 16 hours. The reaction mixture was cooled, diluted with Et2O and water and then separated. The aqueous layer was washed with Et2O, then the combined organics were washed with water, 10% K2CO3, saturated NaCl, dried over Na2SO4 and concentrated in vacuo to provide methyl 2-bromo-3-(3-cyano-5-fluorophenoxy)-6-(methylsulfonyl)benzoate as an orange oil (276 mg, quant.). 1H NMR (400 MHz, CDCl3): delta 8.03 (d, 1H), 7.25-7.22 (m, 1H), 7.14 (d, 1H), 7.10-7.09 (m, 1H), 7.03-7.00 (m, 1H), 4.04 (s, 3H), 3.20 (s, 3H).
  • 31
  • [ 473923-95-4 ]
  • 2-(difluoromethyl)-3-fluoro-6-(methylsulfonyl)benzonitrile [ No CAS ]
  • 3-(3-cyano-5-fluorophenoxy)-2-(difluoromethyl)-6-(methylsulfonyl)benzonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
96% With caesium carbonate; In N,N-dimethyl-formamide; at 20 - 45℃; for 60.0h; A suspension of 2-(difluorornethyl)-3-fluoro-6- (methylsulfonyl)benzonitrile (9.52 g, 38.2 mrnol), <strong>[473923-95-4]3-fluoro-5-hydroxy-benzonitrile</strong> (5.23 g, 38.2 mmol), and cesium carbonate (7.77 g, 40.1 mmol) in IV N-dimethylformamide (76 rnL) was heated to 45 C for 3 hours. Additional cesium carbonate (0.46 g, 1.4 mrnol) was added and the reaction mixture was heated at 45 C for three hours, then stirred at ambient temperature for 54 hours. The reaction mixture was vigorously stirred while water (800 mL) was added. The resulting suspension was stirred for 30 minutes, then the solids were collected by filtration, washed with water (1.2 L), and dried under high vacuum to give 3-(3- cyano-5 -fluorophenoxy)-2-(difluoromethyl)-6-(methylsulfonyl)benzonitrile as a white solid (13.3 g, 96%). LCMS ESI (+) m/z 384 (M+NH4). ?H NMR (400 MHz, DMSO-do): 6 8.22 (d, 1H), 7.86-7.82 (m, 1H), 7.72-7.62 (m, 3H), 7.49 (t, 1H), 3.44 (s, 3H).
96% With caesium carbonate; In water; N,N-dimethyl-formamide; at 20 - 45℃; for 57.0h; Preparation of 3-(3-cyano-5-fluorophenoxy)-2-(difluoromethyl)-6- (methylsulfonyl)benzonitrile: A suspension of 2-(difluoromethyl)-3-fluoro-6- (methylsulfonyl)benzonitrile (9.52 g, 38.2 mmol), <strong>[473923-95-4]3-fluoro-5-hydroxy-benzonitrile</strong> (5.23 g, 38.2 mmol), and cesium carbonate (7.77 g, 40.1 mmol) in N, N-dimethylformamide (76 mL) was heated to 45 C for 3 hours. Additional cesium carbonate (0.46 g, 1.4 mmol) was added and the reaction mixture was heated at 45 C for three hours, then stirred at ambient temperature for 54 hours. The reaction mixture was vigorously stirred while water (800 mL) was added. The resulting suspension was stirred for 30 minutes, then the solids were collected by filtration, washed with water (1.2 L), and dried under high vacuum. 3-(3-Cyano- 5-fluorophenoxy)-2-(difluoromethyl)-6-(methylsulfonyl)benzonitrile was recovered as a white solid (13.3 g, 96%). LCMS ESI (+) m/z 384 (M+NH4). NMR (400 MHz, DMSO- d6): delta 8.22 (d, 1H), 7.86-7.82 (m, 1H), 7.72-7.62 (m, 3H), 7.49 (t, 1H), 3.44 (s, 3H).
96% With caesium carbonate; In N,N-dimethyl-formamide; at 20 - 45℃; for 60.0h; 1005321 Step E: Preparation of 3 -(3 -cyano-5 -fluorophenoxy)-2-(difluoromethyl)-6- (methyl sulfonyl)benzonitrile: A suspension of 2-(difluoromethyl)-3 -fluoro-6- (methyl sulfonyl)benzonitrile (9.52 g, 38.2 mmol), 3 -fluoro-5 -hydroxy-benzonitrile (5.23 g, 38.2 mmol), and cesium carbonate (7.77 g, 40.1 mmol) in N, N-dimethylformamide (76 mL) was heated to 45 C for 3 hours. Additional cesium carbonate (0.46 g, 1.4 mmol) was added and the reaction mixture was heated at 45 C for three hours, then stirred at ambient temperature for 54 hours. The reaction mixture was vigorously stirred while water (800 mL) was added. The resulting suspension was stirred for 30 minutes, then the solids were collected by filtration, washed with water (1.2 L), and dried under high vacuum to give 3-(3- cyano-5 -fluorophenoxy)-2-(difluoromethyl)-6-(methyl sulfonyl)benzonitrile as a white solid(13.3 g, 96%). LCMS ESI (+) m/z 384 (M+NH4). ?H NIVIR (400 MFIz, DMSO-d6): 8.22 (d, 1H), 7.86-7.82 (m, 1H), 7.72-7.62 (m, 3H), 7.49 (t, 1H), 3.44 (s, 3H).
96% With caesium carbonate; In N,N-dimethyl-formamide; at 20 - 45℃; for 57.0h; A suspension of 2-(difluoromethyl)-3-fluoro-6- (methylsulfonyl)benzonitrile (9.52 g, 38.2 mmol), <strong>[473923-95-4]3-fluoro-5-hydroxy-benzonitrile</strong> (5.23 g, 38.2 mmol), and cesium carbonate (7.77 g, 40.1 mmol) in N,N-dimethylformamide (76 mL) was heated to 45 C for 3 hours. Additional cesium carbonate (0.46 g, 1.4 mmol) was added and the reaction mixture was heated at 45 C for three hours, then stirred at ambient temperature for 54 hours. The reaction mixture was vigorously stirred while water (800 mL) was added. The resulting suspension was stirred for 30 minutes, then the solids were collected by filtration, washed with water (1.2 L), and dried under high vacuum to give 3-(3-cyano-5-fluorophenoxy)- 2-(difluoromethyl)-6-(methylsulfonyl)benzonitrile as a white solid (13.3 g, 96%). LCMS ESI (+) m/z 384 (M+ H4). 1H MR (400 MHz, DMSO-d6): delta 8.22 (d, 1H), 7.86-7.82 (m, 1H), 7.72- 7.62 (m, 3H), 7.49 (t, 1H), 3.44 (s, 3H).
96% With caesium carbonate; In N,N-dimethyl-formamide; at 45℃; for 60.0h; A suspension of 2-(difluoromethyl)-3-fluoro-6-(methyl sulfonyl)benzonitrile (9.52 g, 38.2 mmol), <strong>[473923-95-4]3-fluoro-5-hydroxy-benzonitrile</strong> (5.23 g, 38.2 mmol), and cesium carbonate (7.77 g, 40.1 mmol) in N, N-dimethylformamide (76 mL) was heated to 45 C. for 3 hours. Additional cesium carbonate (0.46 g, 1.4 mmol) was added and the reaction mixture was heated at 45 C. for three hours, then stirred at ambient temperature for 54 hours. The reaction mixture was vigorously stirred while water (800 mL) was added. The resulting suspension was stirred for 30 minutes, then the solids were collected by filtration, washed with water (1.2 L), and dried under high vacuum to give 3-(3-cyano-5-fluorophenoxy)-2-(difluoromethyl)-6-(methyl sulfonyl)benzonitrile as a white solid (13.3 g, 96%). LCMS ESI (+) m/z 384 (M+NH4). 1H NMR (400 MHz, DMSO-d6): delta 8.22 (d, 1H), 7.86-7.82 (m, 1H), 7.72-7.62 (m, 3H), 7.49 (t, 1H), 3.44 (s, 3H).

  • 32
  • [ 473923-95-4 ]
  • 3-((4-bromo-1,1-dioxido-3-oxo-2,3-dihydrobenzo[b]thiophen-5-yl)oxy)-5-fluorobenzonitrile [ No CAS ]
  • 33
  • [ 473923-95-4 ]
  • (R)-3-((4-bromo-2,2-difluoro-3-hydroxy-1,1-dioxido-2,3-dihydrobenzo[b]thiophen-5-yl)oxy)-5-fluorobenzonitrile [ No CAS ]
  • (S)-3-((4-bromo-2,2-difluoro-3-hydroxy-1,1-dioxido-2,3-dihydrobenzo[b]thiophen-5-yl)oxy)-5-fluorobenzonitrile [ No CAS ]
  • 34
  • [ 473923-95-4 ]
  • methyl 3-(3-cyano-5-fluoro-phenoxy)-6-methylsulfonyl-2-(2-trimethylsilylethynyl)benzoate [ No CAS ]
  • 35
  • [ 473923-95-4 ]
  • 3-(4-ethynyl-1,1,3-trioxo-benzothiophen-5-yl)oxy-5-fluoro-benzonitrile [ No CAS ]
  • 36
  • [ 473923-95-4 ]
  • 3-(4-ethynyl-2,2-difluoro-1,1,3-trioxo-benzothiophen5-yl)oxy-5-fluoro-benzonitrile [ No CAS ]
  • 37
  • [ 473923-95-4 ]
  • methyl 3-(3-cyano-5-fluorophenoxy)-2-(3-hydroxyprop-1-ynyl)-6-methylsulfonylbenzoate [ No CAS ]
  • 38
  • [ 473923-95-4 ]
  • methyl 3-(3-cyano-5-fluoro-phenoxy)-2-(3-fluoroprop-1-ynyl)-6-methylsulfonylbenzoate [ No CAS ]
  • 39
  • [ 473923-95-4 ]
  • 3-fluoro-5-[4-(3-fluoroprop-1-ynyl)-1,1,3-trioxobenzothiophen-5-yl]oxybenzonitrile [ No CAS ]
  • 40
  • [ 473923-95-4 ]
  • 3-[2,2-difluoro-4-(3-fluoroprop-1-ynyl)-1,1,3-trioxobenzothiophen-5-yl]oxy-5-fluorobenzonitrile [ No CAS ]
  • 41
  • [ 473923-95-4 ]
  • 3-((4-bromo-2,2-difluoro-1,1-dioxido-3-oxo-2,3-dihydrobenzo[b]thiophen-5-yl)oxy)-5-fluorobenzonitrile [ No CAS ]
  • 42
  • [ 473923-95-4 ]
  • 3-((4-ethynyl-2,2-difluoro-3-hydroxy-1,1-dioxido-2,3-dihydrobenzo[b]thiophen-5-yl)oxy)-5-fluorobenzonitrile [ No CAS ]
  • 43
  • [ 473923-95-4 ]
  • 3-[[2,2-difluoro-4-(3-fluoroprop-1-ynyl)-3-hydroxy-1,1-dioxo-3H-benzothiophen-5-yl]oxy]-5-fluorobenzonitrile [ No CAS ]
  • 44
  • [ 473923-95-4 ]
  • methyl 2-chloro-3-fluoro-6-(methylsulfonyl)benzoate [ No CAS ]
  • methyl 2-chloro-3-(3-cyano-5-fluorophenoxy)-6-(methylsulfonyl)benzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
91% With sodium hydrogencarbonate; In N,N-dimethyl-formamide; at 90℃; for 16.0h; Methyl 2 -chloro-3 -fluoro-6-(methylsulfonyl)benzoate (200 mg, 0.75 mmol) was treated with 3-fiuoro-5-hydroxy-benzonitrile (205 rng, 1.5 mmol) and DMF (2.5 mL). The solution was treated with in a single portion with sodium bicarbonate (126 mg, 1.5 mmol) and the mixture was heated to 90C for 16 hours. The reaction was cooled, diluted with Et20 and water, then separated. The aqueous was washed with Et20. The combined organics were washed with water, three times with 10% K2C03, saturated NaCl, dried over Na2SO4 and concentrated in vacuo to an light orange solid (262 mg, 91%). 1H NMR (400 MHz, CDC13): 7.99 (d, 1H), 7.25-7.22 (m, 1H), 7.19 (d, 1H), 7.10-7.09 (m, 1H), 7.03-7.00 (dt, lH), 4.04 (s, 3H), 3.21 (s, 3H).
91% With sodium hydrogencarbonate; In N,N-dimethyl-formamide; at 90℃; for 16.0h; Methyl 2-chloro-3-fluoro-6-(methylsulfonyl)benzoate (200 mg, 0.75 mmol) was treated with 3 -fluoro-5 -hydroxy -benzonitrile (205 mg, 1.5 mmol) and dimethylformamide (2.5 mL). The solution was treated with in a single portion with sodium bicarbonate (126 mg, 1.5 mmol) and the mixture was heated to 90C for 16 hours. The reaction was cooled, diluted with Et20 and water, then separated. The aqueous was washed with Et20. The combined organics were washed with water, three times with 10% K2CO3, saturated NaCl, dried over Na2S04 and concentrated in vacuo to an light orange solid (262 mg, 91%). XH NMR (400 MHz, CDC13): 5 7.99 (d, 1H), 7.25-7.22 (m, 1H), 7.19 (d, 1H), 7.10-7.09 (m, 1H), 7.03-7.00 (dt, 1H), 4.04 (s, 3H), 3.21 (s, 3H).
  • 45
  • [ 473923-95-4 ]
  • C33H45FN8O2Si [ No CAS ]
  • 46
  • [ 473923-95-4 ]
  • (R)-4-(4-{3-[(dimethylamino)methyl]-5-fluorophenoxy}piperidin-1-yl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanenitrile [ No CAS ]
  • (S)-4-(4-{3-[(dimethylamino)methyl]-5-fluorophenoxy}piperidin-1-yl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanenitrile [ No CAS ]
  • 47
  • [ 473923-95-4 ]
  • [methyl-oxo-[1,2,2,7-tetrafluoro-3-oxo-indan-4-yl]-λ6-sulfanylidene]cyanamide [ No CAS ]
  • [[(1R,3S)-7-(3-cyano-5-fluoro-phenoxy)-1,2,2-trifluoro-3-hydroxy-indan-4-yl]-methyl-oxo-λ6-sulfanylidene]cyanamide [ No CAS ]
  • [[(1S,3S)-7-(3-cyano-5-fluoro-phenoxy)-1,2,2-trifluoro-3-hydroxy-indan-4-yl]-methyl-oxo-λ6-sulfanylidene]cyanamide [ No CAS ]
  • 48
  • [ 473923-95-4 ]
  • (E,Z)-3-((1-(butylimino)-7-((difluoromethyl)sulfonyl)-2,3-dihydro-1H-inden-4-yl)oxy)-5-fluorobenzonitrile [ No CAS ]
  • 49
  • [ 473923-95-4 ]
  • 3-fluoro-5-((2-fluoro-7-(methylsulfonyl)-1-oxo-2,3-dihydro-1H-inden-4-yl)oxy)benzonitrile [ No CAS ]
  • 50
  • [ 473923-95-4 ]
  • 3-fluoro-5-(((1S,2R)-2-fIuoro-1-hydroxy-7-(methylsulfonyl)-2,3-dihydro-1H-inden-4-yl)oxy)benzonitrile [ No CAS ]
  • 51
  • [ 473923-95-4 ]
  • 3-((7-((difluoromethyl)sulfonyl)-2,2-difluoro-1-oxo-2,3-dihydro-1H-inden-4-yl)oxy)-5-fluorobenzonitrile [ No CAS ]
  • 52
  • [ 473923-95-4 ]
  • N-((7-(3-cyano-5-fluorophenoxy)-3-oxo-2,3-dihydro-1H-inden-4-yl)(methyl)(oxo)-λ6-sulfanylidene)cyanamide [ No CAS ]
  • 53
  • [ 473923-95-4 ]
  • (E/Z)-N-((7-(3-cyano-5-fluorophenoxy)-3-((3-methoxypropyl)imino)-2,3-dihydro-1H-inden-4-yl)(methyl)(oxo)-λ6-sulfanylidene)cyanamide [ No CAS ]
  • 54
  • [ 473923-95-4 ]
  • N-((7-(3-cyano-5-fluorophenoxy)-2,2-difluoro-3-oxo-2,3-dihydro-1H-inden-4-yl)(methyl)(oxo)-λ6-sulfanylidene)cyanamide [ No CAS ]
  • 55
  • [ 473923-95-4 ]
  • N-(((S)-7-(3-cyano-5-fluorophenoxy)-2,2-difluoro-3-hydroxy-2,3-dihydro-1H-inden-4-yl)(methyl)(oxo)-λ6-sulfanylidene)cyanamide [ No CAS ]
  • 56
  • [ 473923-95-4 ]
  • (S)-3-((7-((difluoromethyl)sulfonyl)-2,2-difluoro-1-hydroxy-2,3-dihydro-1H-inden-4-yl)oxy)-5-fluorobenzonitrile [ No CAS ]
  • 57
  • [ 473923-95-4 ]
  • 7’-(3-cyano-5-fluoro-phenoxy)spiro[1,3-dioxolane-2,3‘-indane]-4’-sulfonamide [ No CAS ]
  • 58
  • [ 473923-95-4 ]
  • 7-(3-cyano-5-fluoro-phenoxy)-3-oxo-indane-4-sulfonamide [ No CAS ]
  • 59
  • [ 473923-95-4 ]
  • 7-(3-cyano-5-fluoro-phenoxy)-2,2-difluoro-3-oxo-indane-4-sulfonamide [ No CAS ]
  • 60
  • [ 473923-95-4 ]
  • (S)-7-(3-cyano-5-fluorophenoxy)-2,2-difluoro-3-hydroxy-2,3-dihydro-1H-indene-4-sulfonamide [ No CAS ]
  • 61
  • [ 473923-95-4 ]
  • 3-fluoro-5-(1-oxo-7-sulfanyl-indan-4-yl)oxy-benzonitrile [ No CAS ]
  • 62
  • [ 473923-95-4 ]
  • 7-(3-cyano-5-fluoro-phenoxy)-3-oxo-indane-4-sulfonyl chloride [ No CAS ]
  • 63
  • [ 473923-95-4 ]
  • 3-((2-chloro-2-fluoro-7-(methylsulfonyl)-1-oxo-2,3-dihydro-1H-inden-4-yl)oxy)-5-fluorobenzonitrile [ No CAS ]
  • 64
  • [ 473923-95-4 ]
  • [(1S,2R)-4-(3-cyano-5-fluoro-phenoxy)-2-fluoro-7-methylsulfonyl-indan-1-yl] acetate [ No CAS ]
  • 65
  • [ 473923-95-4 ]
  • [(1S,2S,3S)-3-bromo-4-(3-cyano-5-fluoro-phenoxy)-2-fluoro-7-methylsulfonyl-indan-1-yl] acetate [ No CAS ]
  • [(1S,2S,3R)-3-bromo-4-(3-cyano-5-fluoro-phenoxy)-2-fluoro-7-methylsulfonyl-indan-1-yl] acetate [ No CAS ]
  • 66
  • [ 473923-95-4 ]
  • [(1S,2R,3S)-4-(3-cyano-5-fluoro-phenoxy)-2-fluoro-3-hydroxy-7-methylsulfonyl-indan-1-yl] acetate [ No CAS ]
  • 67
  • [ 473923-95-4 ]
  • [(1S,2S,3R)-4-(3-cyano-5-fluoro-phenoxy)-2,3-difluoro-7-methylsulfonyl-indan-1-yl] acetate [ No CAS ]
  • 68
  • [ 473923-95-4 ]
  • 3-((7-((difluoromethyl)thio)-1-oxo-2,3-dihydro-1H-inden-4-yl)oxy)-5-fluorobenzonitrile [ No CAS ]
  • 69
  • [ 473923-95-4 ]
  • N-((7-(3-cyano-5-fluorophenoxy)-3-oxo-2,3-dihydro-1H-inden-4-yl)(difluoromethyl)-λ4-sulfanylidene)cyanamide [ No CAS ]
  • 70
  • [ 473923-95-4 ]
  • N-((7-(3-cyano-5-fluorophenoxy)-3-oxo-2,3-dihydro-1H-inden-4-yl)(difluoromethyl)(oxo)-λ6-sulfanylidene)cyanamide [ No CAS ]
  • 71
  • [ 473923-95-4 ]
  • N-(((R)-7-(3-cyano-5-fluorophenoxy)-2-fluoro-3-oxo2,3-dihydro-1H-inden-4-yl)(difluoromethyl)(oxo)-λ6-sulfanylidene)cyanamide [ No CAS ]
  • 72
  • [ 473923-95-4 ]
  • N-(((2R,3S)-7-(3-cyano-5-fluorophenoxy)-2-fluoro-3-hydroxy-2,3-dihydro-1H-inden-4-yl)(difluoromethyl)(oxo)-λ6-sulfanylidene)cyanamide [ No CAS ]
  • 73
  • [ 473923-95-4 ]
  • 3-fluoro-5-(((1S,2S)-2-fluoro-1-hydroxy-2-methyl-7-(methylsulfonyl)-2,3-dihydro-1H-inden-4-yl)oxy)benzonitrile [ No CAS ]
  • 74
  • [ 473923-95-4 ]
  • 3-fluoro-5-((2-fluoro-2-methyl-7-(methylsulfonyl)-1-oxo-2,3-dihydro-1H-inden-4-yl)oxy)benzonitrile [ No CAS ]
  • 75
  • [ 473923-95-4 ]
  • 3-fluoro-5-((2-methyl-7-(methylsulfonyl)-1-oxo-2,3-dihydro-1H-inden-4-yl)oxy)benzonitrile [ No CAS ]
  • 76
  • [ 473923-95-4 ]
  • 3-fluoro-5-(((1R,2R)-1-hydroxy-2-methyl-7-(methylsulfonyl)-2,3-dihydro-1H-inden-4-yl)oxy)benzonitrile [ No CAS ]
  • 77
  • [ 473923-95-4 ]
  • [[7-(3-cyano-5-fluoro-phenoxy)-2-fluoro-3-oxo-indan-4-yl]methyl-oxo-λ6-sulfanylidene]cyanamide [ No CAS ]
  • 78
  • [ 473923-95-4 ]
  • N-(((2R,3S)-7-(3-cyano-5-fluorophenoxy)-2-fluoro-3-hydroxy-2,3-dihydro-1H-inden-4-yl)(methyl)(oxo)-λ6-sulfanylidene)cyanamide [ No CAS ]
  • 79
  • [ 473923-95-4 ]
  • 1‘-bromo-7’-(3-cyano-5-fluoro-phenoxy)spiro[1,3-dioxolane-2,3'indane]-4’-sulfonamide [ No CAS ]
  • 80
  • [ 473923-95-4 ]
  • 7’-(3-cyano-5-fluoro-phenoxy)-1‘-hydroxy-spiro[1,3-dioxolane-2,3'-indane]-4’-sulfonamide [ No CAS ]
  • 81
  • [ 473923-95-4 ]
  • 7’-(3-cyano-5-fluoro-phenoxy)-1‘-oxo-spiro [1,3-dioxolane-2,3'-indane]-4’-sulfonamide [ No CAS ]
  • 82
  • [ 473923-95-4 ]
  • 7-(3-cyano-5-fluoro-phenoxy)-1,3-dioxo-indane-4-sulfonamide [ No CAS ]
  • 83
  • [ 473923-95-4 ]
  • 7-(3-cyano-5-fluoro-phenoxy)-2,2-difluoro-1,3-dioxo-indane-4-sulfonamide [ No CAS ]
  • 84
  • [ 473923-95-4 ]
  • (1R,3S)-7-(3-cyano-5-fluoro-phenoxy)-2,2-difluoro-1,3-dihydroxy-indane-4-sulfonamide [ No CAS ]
  • 85
  • [ 473923-95-4 ]
  • (1R,3S)-7-(3-cyano-5-fluoro-phenoxy)-1,2,2-trifluoro-3-hydroxy-indane-4-sulfonamide [ No CAS ]
Same Skeleton Products
Historical Records

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[ 473923-95-4 ]

Fluorinated Building Blocks

Chemical Structure| 439280-18-9

[ 439280-18-9 ]

3-Fluoro-5-methoxybenzonitrile

Similarity: 0.92

Chemical Structure| 186590-04-5

[ 186590-04-5 ]

4-Fluoro-3-hydroxybenzonitrile

Similarity: 0.92

Chemical Structure| 91407-41-9

[ 91407-41-9 ]

5-Fluoro-2-hydroxybenzonitrile

Similarity: 0.90

Chemical Structure| 140675-43-0

[ 140675-43-0 ]

2-Fluoro-6-hydroxybenzonitrile

Similarity: 0.88

Chemical Structure| 104798-53-0

[ 104798-53-0 ]

2-Fluoro-5-hydroxybenzenecarbonitrile

Similarity: 0.88

Aryls

Chemical Structure| 439280-18-9

[ 439280-18-9 ]

3-Fluoro-5-methoxybenzonitrile

Similarity: 0.92

Chemical Structure| 186590-04-5

[ 186590-04-5 ]

4-Fluoro-3-hydroxybenzonitrile

Similarity: 0.92

Chemical Structure| 91407-41-9

[ 91407-41-9 ]

5-Fluoro-2-hydroxybenzonitrile

Similarity: 0.90

Chemical Structure| 140675-43-0

[ 140675-43-0 ]

2-Fluoro-6-hydroxybenzonitrile

Similarity: 0.88

Chemical Structure| 104798-53-0

[ 104798-53-0 ]

2-Fluoro-5-hydroxybenzenecarbonitrile

Similarity: 0.88

Nitriles

Chemical Structure| 439280-18-9

[ 439280-18-9 ]

3-Fluoro-5-methoxybenzonitrile

Similarity: 0.92

Chemical Structure| 186590-04-5

[ 186590-04-5 ]

4-Fluoro-3-hydroxybenzonitrile

Similarity: 0.92

Chemical Structure| 91407-41-9

[ 91407-41-9 ]

5-Fluoro-2-hydroxybenzonitrile

Similarity: 0.90

Chemical Structure| 140675-43-0

[ 140675-43-0 ]

2-Fluoro-6-hydroxybenzonitrile

Similarity: 0.88

Chemical Structure| 104798-53-0

[ 104798-53-0 ]

2-Fluoro-5-hydroxybenzenecarbonitrile

Similarity: 0.88