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[ CAS No. 1351185-56-2 ] {[proInfo.proName]}

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3d Animation Molecule Structure of 1351185-56-2
Chemical Structure| 1351185-56-2
Chemical Structure| 1351185-56-2
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Product Details of [ 1351185-56-2 ]

CAS No. :1351185-56-2 MDL No. :MFCD26388774
Formula : C8H7FINO Boiling Point : -
Linear Structure Formula :- InChI Key :QAEJBAGSKXLRKI-UHFFFAOYSA-N
M.W : 279.05 Pubchem ID :86683688
Synonyms :

Calculated chemistry of [ 1351185-56-2 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 12
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.12
Num. rotatable bonds : 2
Num. H-bond acceptors : 2.0
Num. H-bond donors : 1.0
Molar Refractivity : 52.11
TPSA : 29.1 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.62 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.76
Log Po/w (XLOGP3) : 1.95
Log Po/w (WLOGP) : 2.21
Log Po/w (MLOGP) : 2.83
Log Po/w (SILICOS-IT) : 2.76
Consensus Log Po/w : 2.3

Druglikeness

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

Water Solubility

Log S (ESOL) : -3.04
Solubility : 0.256 mg/ml ; 0.000919 mol/l
Class : Soluble
Log S (Ali) : -2.19
Solubility : 1.82 mg/ml ; 0.00652 mol/l
Class : Soluble
Log S (SILICOS-IT) : -4.01
Solubility : 0.0271 mg/ml ; 0.0000973 mol/l
Class : Moderately soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 0.0
Synthetic accessibility : 1.78

Safety of [ 1351185-56-2 ]

Signal Word:Danger Class:6.1
Precautionary Statements:P261-P264-P270-P271-P280-P302+P352-P304+P340-P310-P330-P361-P403+P233-P405-P501 UN#:2811
Hazard Statements:H301-H311-H331 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 1351185-56-2 ]

* 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 [ 1351185-56-2 ]

[ 1351185-56-2 ] Synthesis Path-Downstream   1~39

  • 1
  • [ 1351185-56-2 ]
  • (+)-trans-4-{3-[4-cyano-3-(trifluoromethyl)phenyl]-2-oxo-octahydro-1H-1,3-benzodiazol-1-yl}-2-fluoro-N-methylbenzamide [ No CAS ]
  • 2
  • [ 1351185-56-2 ]
  • (±)-trans-4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-2,6-dioxooctahydro-1H-benzo[d]imidazol-1-yl)-2-fluoro-N-methylbenzamide [ No CAS ]
  • 3
  • [ 1351185-56-2 ]
  • (±)-trans-4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-6-hydroxy-2-oxooctahydro-1H-benzo[d]imidazol-1-yl)-2-fluoro-N-methylbenzamide [ No CAS ]
  • 4
  • [ 1351185-56-2 ]
  • (+)-trans-4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-6-hydroxy-2-oxooctahydro-1H-benzo[d]imidazol-1-yl)-2-fluoro-N-methylbenzamide [ No CAS ]
  • (-)-trans-4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-6-hydroxy-2-oxooctahydro-1H-benzo[d]imidazol-1-yl)-2-fluoro-N-methylbenzamide [ No CAS ]
  • 5
  • [ 1351185-56-2 ]
  • (±)-trans-1-(4-cyano-3-(trifluoromethyl)phenyl)-3-(3-fluoro-4-(methylcarbamoyl)phenyl)-2-oxooctahydro-1H-benzo[d]imidazol-5-yl methanesulfonate [ No CAS ]
  • 6
  • [ 1351185-56-2 ]
  • (±)-trans-4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-2-oxo-2,3,3a,4,7,7a-hexahydro-1H-benzo[d]imidazol-1-yl)-2-fluoro-N-methylbenzamide [ No CAS ]
  • (±)-trans-4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-2-oxo-2,3,3a,4,5,7a-hexahydro-1H-benzo[d]imidazol-1-yl)-2-fluoro-N-methylbenzamide [ No CAS ]
  • 7
  • [ 1351185-56-2 ]
  • (-)-trans-4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-2-oxo-2,3,3a,4,7,7a-hexahydro-1H-benzo[d]imidazol-1-yl)-2-fluoro-N-methylbenzamide [ No CAS ]
  • (+)-trans-4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-2-oxo-2,3,3a,4,7,7a-hexahydro-1H-benzo[d]imidazol-1-yl)-2-fluoro-N-methylbenzamide [ No CAS ]
  • 8
  • [ 1351185-56-2 ]
  • 4-{(3aS,7aS)-3-[4-cyano-3-(trifluoromethyl)phenyl]-2-oxo-octahydro-1H-1,3-benzodiazol-1-yl}-2-fluoro-N-methylbenzothioamide [ No CAS ]
  • 9
  • [ 1351185-56-2 ]
  • [ 1443103-68-1 ]
  • (±)-trans-4-(1-(4-cyano-3-(trifluoromethyl)phenyl)-2-oxohexahydrospiro[benzo[d]imidazole-5,2'-[1,3]dioxolan]-3(2H)-yl)-2-fluoro-N-methylbenzamide [ No CAS ]
  • (±)-cis-4-(1-(4-cyano-3-(trifluoromethyl)phenyl)-2-oxohexahydrospiro[benzo[d]imidazole-5,2'-[1,3]dioxolan]-3(2H)-yl)-2-fluoro-N-methylbenzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
17.8%; 17.8% With potassium phosphate; copper(l) iodide; trans-1,2-Diaminocyclohexane; In toluene; for 12h;Sealed tube; A suspension of c/'s- and frans-4-(2-oxohexahydrospiro[benzo[d]imidazole-5,2'- [1 ,3]dioxolan]-1 (6H)-yl)-2-(trifluoromethyl)benzonitrile (±) (0.020 g, 0.054 mmol), 2-fluoro- 4-iodo-A/-methylbenzamide (0.015 g, 0.054 mmol), frans-1 ,2-diaminocyclohexane (±) (0.0012 g, 0.0109 mmol) and tripotassium phosphate (0.034 g, 0.163 mmol) in toluene (4 ml_) was degassed for 30 min in a microwave vial. Cul (0.001 g, 0.054 mmol) was added and the vial was sealed with an aluminum cap. The sealed vial was kept in a preheated oil bath at 1 10 C and stirred for 12 h. The reaction mixture was cooled to RT, filtered through a pad of celite, and the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by column chromatography on silica gel (ethyl acetate/hexane = 8/2) to give a mixture of title the compounds (0.020 g, 71 .4%) as light yellow solids. The above mixture was separated by preparative TLC (hexanes/ethyl acetate = 6/4). The nonpolar isomer (frans-4-(1-(4-cyano-3-(trifluoromethyl)phenyl)-2- oxohexahydrospiro[benzo[ ]imidazole-5,2'-[1 ,3]dioxolan]-3(2/-/)-yl)-2-fluoro-//- methylbenzamide) [racemic (±)] was obtained (0.005 g, 17.8%) as an off white solid. LCMS: m/z 519.5 [M+H]+; H NMR (400 MHz, CDCI3) δ 8.20 (t, 1 H), 7.85 (d, 1 H), 7.75 (s, 1 H), 7.55 (d, 1 H), 7.15 (d, 1 H), 7.05 (d, 1 H), 6.70 (s, 1 H), 4.05 (m, 1 H), 4.00 (m, 4H), 3.80 (m, 1 H), 3.05 (d, 3H), 2.45 (d, 1 H), 2.35 (d, 1 H), 2.05 (d, 1 H), 1 .60-1 .90 (m, 3H). The polar isomer (c;'s-4-(1-(4-cyano-3-(trifluoromethyl)phenyl)-2- oxohexahydrospiro[benzo[ ]imidazole-5,2'-[1 ,3]dioxolan]-3(2/-/)-yl)-2-fluoro-//- methylbenzamide) [racemic (±)] was obtained (0.005 g, 17.8%) as an off white solid. LCMS: m/z 519.5 [M+H]+; H NMR (400 MHz, CDCI3) δ 8.15 (t, 1 H), 7.95 (s, 1 H), 7.85 (d, 1 H), 7.7 (d, 1 H), 7.65 (d, 1 H), 7.18 (d, 1 H), 6.74 (s, 1 H) , 4.65 (q, 1 H), 4.50 (q, 1 H), 3.95 (m, 3H), 3.75 (m, 1 H), 3.05 (d, 3H), 2.20 (m, 2H), 2.05 (m, 1 H), 1 .80 (q, 1 H), 1.70 (m, 2H).
17.8%; 17.8% 0494] A suspension of cis- and trans-4-(2-oxohexahydrospiro[benzo[d]imidazole-5,2′-[1,3]dioxolan]-1(6H)-yl)-2-(trifluoromethyl)benzonitrile (±) (0.020 g, 0.054 mmol), <strong>[1351185-56-2]2-fluoro-4-iodo-N-methylbenzamide</strong> (0.015 g, 0.054 mmol), trans-1,2-diaminocyclohexane (±) (0.0012 g, 0.0109 mmol) and tripotassium phosphate (0.034 g, 0.163 mmol) in toluene (4 mL) was degassed for 30 min in a microwave vial. CuI (0.001 g, 0.054 mmol) was added and the vial was sealed with an aluminum cap. The sealed vial was kept in a preheated oil bath at 110 C. and stirred for 12 h. The reaction mixture was cooled to RT, filtered through a pad of celite, and the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by column chromatography on silica gel (ethyl acetate/hexane=82) to give a mixture of title the compounds (0.020 g, 71.4%) as light yellow solids. The above mixture was separated by preparative TLC (hexanes/ethyl acetate=64). The nonpolar isomer (trans-4-(1-(4-cyano-3-(trifluoromethyl)phenyl)-2-oxohexahydrospiro[benzo[d]imidazole-5,2′-[1,3]dioxolan]-3(2H)-yl)-2-fluoro-N-methylbenzamide) [racemic (±)] was obtained (0.005 g, 17.8%) as an off white solid. LCMS: m/z 519.5 [M+H]+; 1H NMR (400 MHz, CDCl3) δ 8.20 (t, 1H), 7.85 (d, 1H), 7.75 (s, 1H), 7.55 (d, 1H), 7.15 (d, 1H), 7.05 (d, 1H), 6.70 (s, 1H), 4.05 (m, 1H), 4.00 (m, 4H), 3.80 (m, 1H), 3.05 (d, 3H), 2.45 (d, 1H), 2.35 (d, 1H), 2.05 (d, 1H), 1.60-1.90 (m, 3H). The polar isomer (cis-4-(1-(4-cyano-3-(trifluoromethyl)phenyl)-2-oxohexahydrospiro[benzo[d]imidazole-5,2′-[1,3]dioxolan]-3(2H)-yl)-2-fluoro-N-methylbenzamide) [racemic (±)] was obtained (0.005 g, 17.8%) as an off white solid. LCMS: m/z 519.5 [M+H]+; 1H NMR (400 MHz, CDCl3) δ 8.15 (t, 1H), 7.95 (s, 1H), 7.85 (d, 1H), 7.7 (d, 1H), 7.65 (d, 1H), 7.18 (d, 1H), 6.74 (s, 1H), 4.65 (q, 1H), 4.50 (q, 1H), 3.95 (m, 3H), 3.75 (m, 1H), 3.05 (d, 3H), 2.20 (m, 2H), 2.05 (m, 1H), 1.80 (q, 1H), 1.70 (m, 2H).
  • 10
  • [ 1351185-56-2 ]
  • (±)-trans-4-(2-oxooctahydro-1H-benzo[d]imidazol-1-yl)-2-(trifluoromethyl)benzonitrile [ No CAS ]
  • (±)-trans-4-{3-[4-cyano-3-(trifluoromethyl)phenyl]-2-oxo-octahydro-1H-1,3-benzodiazol-1-yl}-2-fluoro-N-methylbenzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
30.3% With potassium phosphate; copper(l) iodide; trans-1,2-Diaminocyclohexane; In toluene; for 12h;Sealed tube; A suspension of frans-4-(2-oxooctahydro-1 /-/-benzo[ ]imidazol-1 -yl)-2-(trifluoromethyl)- benzonitrile [racemic(±)] (0.20 g, 0.65 mmol), 2-fluoro-4-iodo-A/-methylbenzamide (0.18 g, 0.65 mmol), frans-1 ,2-diaminocyclohexane (±) (0.022 g, 0.03 mmol) and tripotassium phosphate (0.866 g, 1.94 mmol) in toluene (10 ml_) was degassed for 30 min in a microwave vial. Cul (0.006 g, 0.03 mmol) was added and the vial was sealed with an aluminum cap. The sealed vial was kept in a preheated oil bath at 1 10 C and stirred for 12 h. The reaction mixture was cooled to RT, filtered through a pad of celite, and the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by column chromatography on silica gel (dichloromethane/methanol = 98/2) to give the title compound (0.090 g, 30.3%) as a white solid. HPLC: 95.2%; LCMS: m/z 461 [M+H]+; H NMR (400 MHz, CDCI3) δ 8.19 (t, 1 H), 7.86 (d, 1 H), 7.76 (d, 1 H), 7.56 (dd, 1 H), 7.18 (dd, 1 H), 7.09 (dd, 1 H) 6.74-6.68 (m, 1 H), 3.76-3.73 (m, 2H), 3.06 (d, 3H), 2.44-2.39 (m, 2H), 2.06 (d, 2H), 1.66-1 .52 (m, 4H). The enantiomeric mixture was separated by preparative Chiral HPLC to give example 1 a 7rans-4-{3-[4-cyano-3- (trifluoromethyl)phenyl]-2-oxo-octahydro-1 H-1 ,3-benzodiazol-1 -yl}-2-fluoro-W- Methylbenzamide (+) [0.037 g, retention time: 4.183 min, [a]D25 = + 86 (c = 0.105, MeOH), HPLC: 95.47%] and example 1 b 7rans-4-{3-[4-cyano-3- (trifluoromethyl)phenyl]-2-oxo-octahydro-1 H-1 ,3-benzodiazol-1 -yl}-2-fluoro-W- Methylbenzamide (-) [0.045 g, retention time: 5.536 min, [a]D25 = - 86 (c = 0.106, MeOH), HPLC: 99.32%] as white solids. Method: Column: LUXAMYLOSE; Mobile phase: Heptane (A)/Ethanol (B); Isocratic: 50:50: A: B; Flow: 20 imL/min.
30.3% [0272] A suspension oftrans-4-(2-oxooctahydro-1H-benzo[d]imidazol-1-yl)-2-(trifluoromethyl)-benzonitrile[racemic(±)] (0.20 g, 0.65 mmol),<strong>[1351185-56-2]2-fluoro-4-iodo-N-methylbenzamide</strong> (0.18 g, 0.65 mmol),trans-1,2-diaminocyclohexane (±) (0.022 g, 0.03 mmol) and tripotassium phosphate (0.866 g, 1.94 mmol)in toluene (10 mL) was degassed for 30min in a microwave vial. CuI (0.006 g,0.03 mmol) was added and the vial was sealed with an aluminum cap. The sealedvial was kept in a preheated oil bath at 110 C. and stirred for 12 h. Thereaction mixture was cooled to RT, filtered through a pad of celite, and thefiltrate was concentrated under reduced pressure to give a residue. The residuewas purified by column chromatography on silica gel (dichloromethane/methanol=982)to give the title compound (0.090 g,30.3%) as a white solid. HPLC: 95.2%; LCMS: m/z 461 [M+H]+; 1H NMR (400 MHz,CDCl3) δ 8.19 (t, 1H), 7.86 (d, 1H), 7.76 (d, 1H), 7.56 (dd, 1H), 7.18 (dd,1H), 7.09 (dd, 1H) 6.74-6.68 (m, 1H), 3.76-3.73 (m, 2H), 3.06 (d, 3H),2.44-2.39 (m, 2H), 2.06 (d, 2H), 1.66-1.52 (m, 4H).
  • 11
  • [ 1351185-56-2 ]
  • (±)-trans-4-(2-oxooctahydro-1H-benzo[d]imidazol-1-yl)-2-(trifluoromethyl)benzonitrile [ No CAS ]
  • (+)-trans-4-{3-[4-cyano-3-(trifluoromethyl)phenyl]-2-oxo-octahydro-1H-1,3-benzodiazol-1-yl}-2-fluoro-N-methylbenzamide [ No CAS ]
  • (-)-trans-4-{3-[4-cyano-3-(trifluoromethyl)phenyl]-2-oxo-octahydro-1H-1,3-benzodiazol-1-yl}-2-fluoro-N-methylbenzamide [ No CAS ]
  • 12
  • [ 915087-25-1 ]
  • [ 1351185-56-2 ]
YieldReaction ConditionsOperation in experiment
83% The mixture of 4-amino-2-fluoro-Nmethylbenzamide(22) (1.68 g, 10 mmol) [35], H2SO4 (0.68 mL) andwater (13 mL) was gently heated until all the components werecompletely dissolved. The mixture was cooled to 0e5 understirring, then the solution of NaNO2 (0.7 g,10 mmol) inwater (2 mL)was added dropwise. The resulting mixture was stirred at 0e5for 0.5 h and then slowly poured into the solution of KI (5 g) in coldwater (20 mL). The solutionwas then heated up to 80 and stirredfor 0.5 h. After cooling it was treated with 30 mL of chloroform andfiltered. The organic layer was washed with 5% Na2SO3 solution,dried over Na2SO4 and rotovapped. Column chromatography onsilica gel (hexane/EtOAc 6:1) afforded 2.33 g (83%) of 2-fluoro-4-iodo-N-methylbenzamide (37). MS (ESI) [MH] 280. 1H NMR(400 MHz, DMSO-d6) d 8.25 (m, 1H), 7.73 (d, J 10.0 Hz, 1H), 7.65 (d,J 7.8 Hz, 1H), 7.37 (t, J 7.8 Hz, 1H), 2.75 (d, J 4.4 Hz, 3H). Thesolution of compound 37 (9 g, 32 mmol) in DMF (25 mL) was addedto the ice cooled suspension of NaH (1.48 g, 36.8 mmol, 60% in oil,washed with hexane) in DMF (50 mL). The resulting mixture wasvigorously stirred for 0.5 h in an ice bath, then SEM-chloride (6.46 g,39 mmol) was added and the mixture was continuously stirredovernight at the ambient temperature. After the reaction wascompleted, the mixture was poured into water (400 mL) and theobtained product was extracted with benzene (2 200 mL),washed with water, dried over Na2SO4 and then filtered through3 cm layer of silica gel washing with 5:1 hexane/EtOAc. The solventwas evaporated in vacuo providing 11 g (84%) of 2-fluoro-4-iodo-Nmethyl-N-[2-(trimethylsilyl)ethoxymethyl]benzamide (40). MS(ESI) [MH] 520. 1H NMR (400 MHz, CDCl3) d 7.58 (m,1H), 7.52 (m,1H), 7.12 (m, 1H), 5.01 (s, 0.8H), 4.58 (s, 1.2H), 3.63 (t, J 8.2 Hz,0.8H), 3.31 (t, J 8.2 Hz, 1.2H), 3.14 (s, 1.8H), 2.92 (d, J 0.8 Hz,1.2H), 0.99 (t, J 8.2 Hz, 0.8H), 0.82 (t, J 8.2 Hz, 1.2H), 0.04 (s,3.6), 0.01 (s, 5.4). The mixture of 6.69 g (51 mmol) of aminoacid(R)-36a or 9.55 g of (R)-36b, 17.4 g (42.5 mmol) of 40, 1.62 g(8.5 mmol) of CuI, 23.5 g (0.17 mol) of K2CO3, 36mL of water,145mLof DMF and 3e5 drops of Et3N was stirred for 10 min, then 6.56 g (46.8 mmol) of 2-acetylcyclohexanone was added and stirringcontinued at 100 for 24 h. After cooling the mixture was rotovapped,the residue was treated with 200mL of water and acidifiedwith hydrochloric acid to 2e3 (~30 mL). Then 200 mL of etherwas added, the mixture was stirred for 0.5 h and the formed precipitatewas filtered off, washed with 50 mL of ether and dried invacuo to give 10.7 g (65%) of (R)-3-(3-fluoro-4-{methyl[2-(trimethylsilyl)ethoxymethyl]carbamoyl}phenylamino)-tetrahydrofuran-3-carboxylic acid ((R)-41) (55% from ester (R)-36b). MS (ESI)[MH] 413. 1H NMR (400 MHz, DMSO-d6) d 12.97 (brs, 1H), 7.07(m, 2H), 6.31 (brs, 1H), 6.17 (brs, 1H), 4.85 (brs, 0.67H), 4.60 (brs,1.33H), 4.10 (brs, 1H), 3.87 (brs, 3H), 3.51 (brs, 0.67H), 3.24 (brs,1.33H), 2.93 (s, 2H), 2.86 (brs, 1H), 2.56 (brs, 1H), 2.16 (brs, 1H), 0.89(brs, 0.67H), 0.73 (brs, 1.33H), 0.03 (m, 9H). The mixture of 10.7 g(26 mmol) of (R)-41 and 8.9 g (39 mmol) of 4-isothiocyanato-2-(trifluoromethyl)benzonitrile (42) [34] in pyridine (100 mL) wasstirred at 80 for 48 h. The residue formed after cooling androtovapping was then treated with ethyl acetate and filteredthrough 2 cm layer of silica gel. The solvent was removed underreduced pressure and the desired product was crystallized fromethanol to obtain 4.85 g (30%) of 4-{(R)-3-[4-cyano-3-(trifluoromethyl)phenyl]-4-oxo-2-thioxo-7-oxa-1,3-diazaspiro[4.4]non-1-yl}-2-fluoro-N-methyl-N-[2-(trimethylsilyl)ethoxymethyl]benzamide ((R)-43). MS (ESI) [MH] 623. 1H NMR (400 MHz,CDCl3) d 8.01 (d, J 8.0 Hz, 1), 7.98 (s, 1), 7.85 (d, J 8.0 Hz, 1),7.57 (m, 1), 7.28 (m, 1), 7.21 (m, 1), 5.06 (s, 0.8), 4.63 (s, 1.2),4.41 (d, J 10.4 Hz, 1), 4.16 (d, J 10.4 Hz, 1), 3.97 (q, J 7.6 Hz,1), 3.78 (m, 1), 3.66 (t, J 8.2 Hz, 0.8), 3.66 (t, J 8.2 Hz, 1.2),3.20 (s, 1.8), 2.99 (s, 0.8), 2.72 (m, 1), 2.47 (m, 1), 1.01 (t,J 8.2 Hz, 0.8), 0.83 (t, J 8.2 Hz, 1.2), 0.06 (s, 3.6), 0.01 (s,5.4). TFA (15 mL) was added to the solution of compound (R)-43(4.8 g, 7.7 mmol) in DCM (30 mL), then the resulting mixture wasstirred for 3 h. The solvent was removed under reduced pressureand the formed residue was subjected to column chromatographyon silica gel (CHCl3/MeOH 60:1) to give 2.96 g (78%) of desiredproduct (R)-6.
81.8% To a suspension of 4-amino-2-fluoro-A/-methylbenzamide (20.0 g, 1 18.9 mmol) in 5N HCI (200 mL) was added a solution of NaN02 (12.3 g, 178.4 mmol) in water (80 mL) at 0 C. The reaction mixture was stirred for 30 min at the same temperature. A solution of Kl (43.4 g, 261.5 mmol) in water (80 mL) was added slowly to the above reaction mixture over a period of 20 min at 0 C. The resulting reaction mixture was allowed to warm to RT and stirred for 1 h. The reaction mixture was neutralized with 5N NaOH and extracted with ethyl acetate (150 mL x 3). The combined organic layer was washed with water (100 mL x 2), dried over Na2S04, and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography on silica gel (hexanes/ethyl acetate = 3/1 ) to give the title compound (27.0 g, 81.8%) as a white solid. H NMR (400 MHz, CDCI3) delta 7.82 (t, 1 H), 7.62 (d, 1 H), 7.51 (d, 1 H), 6.74-6.62 (bs, 1 H), 3.02 (d, 3H).
81.8% 0269] To a suspension of <strong>[915087-25-1]4-amino-2-fluoro-N-methylbenzamide</strong> (20.0 g, 118.9 mmol) in 5N HCl (200 mL) was added a solution of NaNO2 (12.3 g, 178.4 mmol) in water (80 mL) at 0 C. The reaction mixture was stirred for 30 min at the same temperature. A solution of Kl (43.4 g, 261.5 mmol) in water (80 mL) was added slowly to the above reaction mixture over a period of 20 min at 0 C. The resulting reaction mixture was allowed to warm to RT and stirred for 1 h. The reaction mixture was neutralized with 5N NaOH and extracted with ethyl acetate (150 mL×3). The combined organic layer was washed with water (100 mL×2), dried over Na2SO4, and concentrated under reduced pressure to give a residue. [0270] The residue was purified by column chromatography on silica gel (hexanes/ethyl acetate=31) to give the title compound (27.0 g, 81.8%) as a white solid. 1H NMR (400 MHz, CDCl3) delta 7.82 (t, 1H), 7.62 (d, 1H), 7.51 (d, 1H), 6.74-6.62 (bs, 1H), 3.02 (d, 3H).
  • 13
  • [ 1351185-56-2 ]
  • [ 56-40-6 ]
  • [ 1351185-57-3 ]
YieldReaction ConditionsOperation in experiment
50% With copper(l) iodide; potassium carbonate; In N,N-dimethyl-formamide; at 140℃;Microwave irradiation; Themixture of compound 37 (279 mg, 1 mmol), glycine (80 mg,1.07 mmol), 2CO3 (207 mg, 1.5 mmol) and CuI (19 mg, 0.1 mmol)dissolved in DMF (3 mL) was kept in microwave reactor for 20 minat 140 C. After cooling the mixture was diluted with 10 mL of ethylacetate and 10 mL of water, neutralized with hydrochloric acid topH 2e3 and the product was extracted with 5 20 mL of ethylacetate. The extracts were washed with brine, dried over Na2SO4and the solvent was evaporated in vacuo. The product was thensubjected to HPLC providing 113 mg (50%) of [3-fluoro-4-(methylcarbamoyl)phenylamino]acetic acid (67). MS (ESI) [MH] 227.The mixture of compound 67 (113 mg, 0.5 mmol) and 42 (174 mg,1.0 mmol) dissolved in DMF (2 mL) was stirred for 12 h at 90 C. Thecooled solutionwas then rotovapped and subjected to HPLC to give86 mg (39%) of compound 12. MS (ESI) [MH] 437. 1H NMR(400 MHz, DMSO-d6) d 8.39 (d, J 8.4 Hz, 1H), 8.32 (m, 1H), 8.17 (s,1H), 7.99 (dd, J1 8.0 Hz, J2 1.4 Hz, 1H), 7.86 (dd, J1 12.0 Hz,J2 1.4 Hz, 1H), 7.75 (m, 2H), 4.95 (s, 2H), 2.79 (d, J 4.4 Hz, 3H).ESIHRMS m/z calcd for C19H13F4N4O2S [MH] 437.0690; found437.0686.
With potassium carbonate; In N,N-dimethyl-formamide; at 140℃; for 0.3h;Microwave irradiation; EXAMPLE 1 Synthesis of N-methyl-4-{4-oxo-2-thioxo-3-[3-(trifluoromethyl)-4-cyanophenyl]imidazolidin-1-yl}-2-fluorobenzamide 1.2(1). Glycine (80 mg, 1.07 mmol) and K2CO3 (207 mg, 1.5 mmol) were added to solution of 4-iodo-N-methyl-2-fluorobenzamide (279 mg, 1 mmol) in DMF (3 ml). The reaction mixture was stirred at 140 C. for 18 min. in microwave oven, cooled, diluted with AcOEt (10 ml) and water (10 ml), neutralized with HCl to pH 2-3, organic layer was separated, water layer was extracted with AcOEt (5*20 ml). The combined extracts were washed with brine, dried over Na2SO4 and evaporated in vacuo. The product was isolated by colomn chromatography on SiO2. It gave N-(4-methylcarbamoyl-2-fluorophenyl)glycine 4.2(1) (R1=CH3, R4=R5=H,). A solution of N-(4-methylcarbamoyl-2-fluorophenyl)glycine 4.2(1) (113 mg, 0.5 mmol) and 4-isothiocyanato-2-(trifluoromethyl)benzonirile 3.2 (174 mg, 1.0 mmol) in DMF (2 ml) was stirred at 90 C. for 12 h. The reaction mixture was evaporated in vacuo, and N-methyl-4-{4-oxo-2-thioxo-3-[3-(trifluoromethyl)-4-cyanophenyl]-imidazolidin-1-yl}-2-fluorobenzamide 1.2(1), was isolated by HPLC method, LCMS (M+H)| 437.
  • 15
  • [ 1351185-56-2 ]
  • 4-((3aS,7aS)-3-(4-cyano-3-(trifluoromethyl)phenyl)-2-oxooctahydro-1H-benzo[d]imidazol-1-yl)-2-fluoro-N-methylbenzothioamide [ No CAS ]
  • 16
  • [ 1351185-56-2 ]
  • trans-1-(4-cyano-3-(trifluoromethyl)phenyl)-3-(3-fluoro-4-(methylcarbamoyl)phenyl)-2-oxooctahydro-1H-benzo[d]imidazol-5-yl methanesulfonate [ No CAS ]
  • 17
  • [ 1351185-56-2 ]
  • (-)-trans-4-{3-[4-cyano-3-(trifluoromethyl)phenyl]-2-oxo-octahydro-1H-1,3-benzodiazol-1-yl}-2-fluoro-N-methylbenzamide [ No CAS ]
  • 19
  • [ 1351185-56-2 ]
  • (R)-3-(3-fluoro-4-{methyl[2-(trimethylsilyl)ethoxymethyl]carbamoyl}phenylamino)-tetrahydrofuran-3-carboxylic acid [ No CAS ]
  • 20
  • [ 1351185-56-2 ]
  • C23H37FN2O5Si [ No CAS ]
  • 21
  • [ 1351185-56-2 ]
  • 4-{(R)-3-[4-cyano-3-(trifluoromethyl)phenyl]-4-oxo-2-thioxo-7-oxa-1,3-diazaspiro[4.4]non-1-yl}-2-fluoro-N-methyl-N-[2-(trimethylsilyl)ethoxymethyl]benzamide [ No CAS ]
  • 22
  • [ 1351185-56-2 ]
  • (R)-3-(4-methylcarbamoyl-3-fluorophenylamino)tetrahydrofuran-3-enoic acid methyl ester [ No CAS ]
  • 23
  • [ 1351185-56-2 ]
  • 3-(3-fluoro-4-{methyl-[2-(trimethylsilyl)ethoxymethyl]carbamoyl}phenylamino)oxetane-3-carboxylic acid [ No CAS ]
  • 24
  • [ 1351185-56-2 ]
  • 3-[3-fluoro-4-(methylcarbamoyl)phenylamino]oxetane-3-carboxylic acid [ No CAS ]
  • 25
  • [ 1351185-56-2 ]
  • methyl 3-(3-fluoro-4-{methyl-[2-(trimethylsilyl)ethoxymethyl]carbamoyl}phenylamino)oxetane-3-carboxylate [ No CAS ]
  • 26
  • [ 1351185-56-2 ]
  • methyl 3-[3-fluoro-4-(methylcarbamoyl)phenylamino]oxetane-3-carboxylate [ No CAS ]
  • 27
  • [ 1351185-56-2 ]
  • N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[3-fluoro-4-(methylcarbamoyl)phenylamino]oxetane-3-carboxamide [ No CAS ]
  • 28
  • [ 1351185-56-2 ]
  • [ 1351185-33-5 ]
  • 29
  • [ 1351185-56-2 ]
  • [ 1351185-35-7 ]
  • 30
  • [ 1351185-56-2 ]
  • [ 1351185-34-6 ]
  • 31
  • [ 1351185-56-2 ]
  • 4-{3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-bis(methoxymethyl)-4-oxo-2-thioxoimidazolidin-1-yl}-2-fluoro-N-methylbenzamide [ No CAS ]
  • 32
  • [ 1351185-56-2 ]
  • 2-(3-fluoro-4-{methyl[2-(trimethylsilyl)ethoxymethyl]carbamoyl}phenylamino)-3-methoxy-2-(methoxymethyl)propanoic acid [ No CAS ]
  • 33
  • [ 1351185-56-2 ]
  • 4-{3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-bis(methoxymethyl)-4-oxo-2-thioxoimidazolidin-1-yl}-2-fluoro-N-methyl-N-[2-(trimethylsilyl)ethoxymethyl]benzamide [ No CAS ]
  • 34
  • [ 1351185-56-2 ]
  • [ 76513-69-4 ]
  • 2-fluoro-4-iodo-N-methyl-N-[2-(trimethylsilyl)ethoxymethyl]benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
84% The mixture of 4-amino-2-fluoro-Nmethylbenzamide(22) (1.68 g, 10 mmol) [35], H2SO4 (0.68 mL) andwater (13 mL) was gently heated until all the components werecompletely dissolved. The mixture was cooled to 0e5 understirring, then the solution of NaNO2 (0.7 g,10 mmol) inwater (2 mL)was added dropwise. The resulting mixture was stirred at 0e5for 0.5 h and then slowly poured into the solution of KI (5 g) in coldwater (20 mL). The solutionwas then heated up to 80 and stirredfor 0.5 h. After cooling it was treated with 30 mL of chloroform andfiltered. The organic layer was washed with 5% Na2SO3 solution,dried over Na2SO4 and rotovapped. Column chromatography onsilica gel (hexane/EtOAc 6:1) afforded 2.33 g (83%) of <strong>[1351185-56-2]2-fluoro-4-iodo-N-methylbenzamide</strong> (37). MS (ESI) [MH] 280. 1H NMR(400 MHz, DMSO-d6) d 8.25 (m, 1H), 7.73 (d, J 10.0 Hz, 1H), 7.65 (d,J 7.8 Hz, 1H), 7.37 (t, J 7.8 Hz, 1H), 2.75 (d, J 4.4 Hz, 3H). Thesolution of compound 37 (9 g, 32 mmol) in DMF (25 mL) was addedto the ice cooled suspension of NaH (1.48 g, 36.8 mmol, 60% in oil,washed with hexane) in DMF (50 mL). The resulting mixture wasvigorously stirred for 0.5 h in an ice bath, then SEM-chloride (6.46 g,39 mmol) was added and the mixture was continuously stirredovernight at the ambient temperature. After the reaction wascompleted, the mixture was poured into water (400 mL) and theobtained product was extracted with benzene (2 200 mL),washed with water, dried over Na2SO4 and then filtered through3 cm layer of silica gel washing with 5:1 hexane/EtOAc. The solventwas evaporated in vacuo providing 11 g (84%) of 2-fluoro-4-iodo-Nmethyl-N-[2-(trimethylsilyl)ethoxymethyl]benzamide (40). MS(ESI) [MH] 520. 1H NMR (400 MHz, CDCl3) d 7.58 (m,1H), 7.52 (m,1H), 7.12 (m, 1H), 5.01 (s, 0.8H), 4.58 (s, 1.2H), 3.63 (t, J 8.2 Hz,0.8H), 3.31 (t, J 8.2 Hz, 1.2H), 3.14 (s, 1.8H), 2.92 (d, J 0.8 Hz,1.2H), 0.99 (t, J 8.2 Hz, 0.8H), 0.82 (t, J 8.2 Hz, 1.2H), 0.04 (s,3.6), 0.01 (s, 5.4). The mixture of 6.69 g (51 mmol) of aminoacid(R)-36a or 9.55 g of (R)-36b, 17.4 g (42.5 mmol) of 40, 1.62 g(8.5 mmol) of CuI, 23.5 g (0.17 mol) of K2CO3, 36mL of water,145mLof DMF and 3e5 drops of Et3N was stirred for 10 min, then 6.56 g (46.8 mmol) of 2-acetylcyclohexanone was added and stirringcontinued at 100 for 24 h. After cooling the mixture was rotovapped,the residue was treated with 200mL of water and acidifiedwith hydrochloric acid to 2e3 (~30 mL). Then 200 mL of etherwas added, the mixture was stirred for 0.5 h and the formed precipitatewas filtered off, washed with 50 mL of ether and dried invacuo to give 10.7 g (65%) of (R)-3-(3-fluoro-4-{methyl[2-(trimethylsilyl)ethoxymethyl]carbamoyl}phenylamino)-tetrahydrofuran-3-carboxylic acid ((R)-41) (55% from ester (R)-36b). MS (ESI)[MH] 413. 1H NMR (400 MHz, DMSO-d6) d 12.97 (brs, 1H), 7.07(m, 2H), 6.31 (brs, 1H), 6.17 (brs, 1H), 4.85 (brs, 0.67H), 4.60 (brs,1.33H), 4.10 (brs, 1H), 3.87 (brs, 3H), 3.51 (brs, 0.67H), 3.24 (brs,1.33H), 2.93 (s, 2H), 2.86 (brs, 1H), 2.56 (brs, 1H), 2.16 (brs, 1H), 0.89(brs, 0.67H), 0.73 (brs, 1.33H), 0.03 (m, 9H). The mixture of 10.7 g(26 mmol) of (R)-41 and 8.9 g (39 mmol) of 4-isothiocyanato-2-(trifluoromethyl)benzonitrile (42) [34] in pyridine (100 mL) wasstirred at 80 for 48 h. The residue formed after cooling androtovapping was then treated with ethyl acetate and filteredthrough 2 cm layer of silica gel. The solvent was removed underreduced pressure and the desired product was crystallized fromethanol to obtain 4.85 g (30%) of 4-{(R)-3-[4-cyano-3-(trifluoromethyl)phenyl]-4-oxo-2-thioxo-7-oxa-1,3-diazaspiro[4.4]non-1-yl}-2-fluoro-N-methyl-N-[2-(trimethylsilyl)ethoxymethyl]benzamide ((R)-43). MS (ESI) [MH] 623. 1H NMR (400 MHz,CDCl3) d 8.01 (d, J 8.0 Hz, 1), 7.98 (s, 1), 7.85 (d, J 8.0 Hz, 1),7.57 (m, 1), 7.28 (m, 1), 7.21 (m, 1), 5.06 (s, 0.8), 4.63 (s, 1.2),4.41 (d, J 10.4 Hz, 1), 4.16 (d, J 10.4 Hz, 1), 3.97 (q, J 7.6 Hz,1), 3.78 (m, 1), 3.66 (t, J 8.2 Hz, 0.8), 3.66 (t, J 8.2 Hz, 1.2),3.20 (s, 1.8), 2.99 (s, 0.8), 2.72 (m, 1), 2.47 (m, 1), 1.01 (t,J 8.2 Hz, 0.8), 0.83 (t, J 8.2 Hz, 1.2), 0.06 (s, 3.6), 0.01 (s,5.4). TFA (15 mL) was added to the solution of compound (R)-43(4.8 g, 7.7 mmol) in DCM (30 mL), then the resulting mixture wasstirred for 3 h. The solvent was removed under reduced pressureand the formed residue was subjected to column chromatographyon silica gel (CHCl3/MeOH 60:1) to give 2.96 g (78%) of desiredproduct (R)-6.
  • 35
  • [ 1351185-56-2 ]
  • butyl (R)-3-aminotetrahydrofuran-3-carboxylate [ No CAS ]
  • (R)-3-[3-fluoro-4-(methylcarbamoyl)phenylamino]tetrahydrofuran-3-carboxylic acid [ No CAS ]
  • C21H21F2N3O5 [ No CAS ]
  • 36
  • [ 1351185-56-2 ]
  • [ 302-72-7 ]
  • [ 1351185-58-4 ]
YieldReaction ConditionsOperation in experiment
With copper(l) iodide; dimethylaminoacetic acid; caesium carbonate; In dimethyl sulfoxide; at 90℃; for 20h; General procedure: D,L-, D- or L-alanine (69) (638 mg, 7.16 mmol),Cs2CO3 (2.337 g, 7.17 mmol), CuI (68 mg, 0.358 mmol) and N,Ndimethylglycine(74 mg, 0.717 mmol) were added to the solution ofcompound 37 (1 g, 3.58 mmol) in DMSO (2.5 mL). The resultingmixture was stirred for 20 h at 90. After cooling the mixture wasfreeze-dried, the residue was extracted with ethanol and theextract was subjected to HPLC to obtain 413e450 mg (24e26%) of2-[3-fluoro-4-(methylcarbamoyl)phenylamino]propionic acid((R,S)-69, (R)-69, (S)-69). (R,S)-69: MS (ESI) [MH] 241. 1H NMR(400 MHz, DMSO-d6) d 12.66 (brs, 1H), 7.62 (m, 1H), 7.45 (t,J 8.8 Hz, 1H), 6.67 (d, J 7.2 Hz, 1H), 6.42 (dd, J1 8.4 Hz,J2 2.0 Hz, 1H), 6.29 (dd, J1 14.8 Hz, J2 2.0 Hz, 1H), 4.03 (m, 1H),2.73 (d, J 4.4 Hz, 3H), 1.37 (d, J 7.2 Hz, 3H). Compound 42(104 mg, 0.456 mmol) was added to the solution of (R,S)-69, (R)-69or (S)-69 (100 mg, 0.416 mmol) in DMF (1 mL). The resultingmixture was stirred for 18 h at 80, then the solvent was removedunder reduced pressure and the product was subjected to HPLC toafford 28e37 mg (15e20%) of (R,S)-13, (R)-13 or (S)-13. (R,S)-13: MS(ESI) [MH] 451. 1H NMR (400 MHz, CDCl3) d 8.28 (t, J 8.6 Hz,1H), 8.01 (d, J 8.0 Hz, 1H), 7.94 (d, J 1.2 Hz, 1H), 7.81 (dd,J1 8.0 Hz, J2 1.2 Hz, 1H), 7.48 (dd, J1 12.4 Hz, J2 1.6 Hz, 1H),7.36 (dd, J1 8.4 Hz, J2 1.6 Hz, 1H), 6.72 (m, 1H), 4.83 (q, J 7.2 Hz,1H), 3.08 (d, J 4.8 Hz, 3H), 1.60 (d, J 7.2 Hz, 3H). ESIHRMS m/zcalcd for C20H15F4N4O2S [MH] 451.0846; found 451.0844.
  • 37
  • [ 338-69-2 ]
  • [ 1351185-56-2 ]
  • 2-[3-fluoro-4-(methylcarbamoyl)phenylamino]propionic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
With copper(l) iodide; dimethylaminoacetic acid; caesium carbonate; In dimethyl sulfoxide; at 90℃; for 20h; General procedure: D,L-, D- or L-alanine (69) (638 mg, 7.16 mmol),Cs2CO3 (2.337 g, 7.17 mmol), CuI (68 mg, 0.358 mmol) and N,Ndimethylglycine(74 mg, 0.717 mmol) were added to the solution ofcompound 37 (1 g, 3.58 mmol) in DMSO (2.5 mL). The resultingmixture was stirred for 20 h at 90. After cooling the mixture wasfreeze-dried, the residue was extracted with ethanol and theextract was subjected to HPLC to obtain 413e450 mg (24e26%) of2-[3-fluoro-4-(methylcarbamoyl)phenylamino]propionic acid((R,S)-69, (R)-69, (S)-69). (R,S)-69: MS (ESI) [MH] 241. 1H NMR(400 MHz, DMSO-d6) d 12.66 (brs, 1H), 7.62 (m, 1H), 7.45 (t,J 8.8 Hz, 1H), 6.67 (d, J 7.2 Hz, 1H), 6.42 (dd, J1 8.4 Hz,J2 2.0 Hz, 1H), 6.29 (dd, J1 14.8 Hz, J2 2.0 Hz, 1H), 4.03 (m, 1H),2.73 (d, J 4.4 Hz, 3H), 1.37 (d, J 7.2 Hz, 3H). Compound 42(104 mg, 0.456 mmol) was added to the solution of (R,S)-69, (R)-69or (S)-69 (100 mg, 0.416 mmol) in DMF (1 mL). The resultingmixture was stirred for 18 h at 80, then the solvent was removedunder reduced pressure and the product was subjected to HPLC toafford 28e37 mg (15e20%) of (R,S)-13, (R)-13 or (S)-13. (R,S)-13: MS(ESI) [MH] 451. 1H NMR (400 MHz, CDCl3) d 8.28 (t, J 8.6 Hz,1H), 8.01 (d, J 8.0 Hz, 1H), 7.94 (d, J 1.2 Hz, 1H), 7.81 (dd,J1 8.0 Hz, J2 1.2 Hz, 1H), 7.48 (dd, J1 12.4 Hz, J2 1.6 Hz, 1H),7.36 (dd, J1 8.4 Hz, J2 1.6 Hz, 1H), 6.72 (m, 1H), 4.83 (q, J 7.2 Hz,1H), 3.08 (d, J 4.8 Hz, 3H), 1.60 (d, J 7.2 Hz, 3H). ESIHRMS m/zcalcd for C20H15F4N4O2S [MH] 451.0846; found 451.0844.
  • 38
  • [ 56-41-7 ]
  • [ 1351185-56-2 ]
  • 2-[3-fluoro-4-(methylcarbamoyl)phenylamino]propionic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
With copper(l) iodide; dimethylaminoacetic acid; caesium carbonate; In dimethyl sulfoxide; at 90℃; for 20h; General procedure: D,L-, D- or L-alanine (69) (638 mg, 7.16 mmol),Cs2CO3 (2.337 g, 7.17 mmol), CuI (68 mg, 0.358 mmol) and N,Ndimethylglycine(74 mg, 0.717 mmol) were added to the solution ofcompound 37 (1 g, 3.58 mmol) in DMSO (2.5 mL). The resultingmixture was stirred for 20 h at 90. After cooling the mixture wasfreeze-dried, the residue was extracted with ethanol and theextract was subjected to HPLC to obtain 413e450 mg (24e26%) of2-[3-fluoro-4-(methylcarbamoyl)phenylamino]propionic acid((R,S)-69, (R)-69, (S)-69). (R,S)-69: MS (ESI) [MH] 241. 1H NMR(400 MHz, DMSO-d6) d 12.66 (brs, 1H), 7.62 (m, 1H), 7.45 (t,J 8.8 Hz, 1H), 6.67 (d, J 7.2 Hz, 1H), 6.42 (dd, J1 8.4 Hz,J2 2.0 Hz, 1H), 6.29 (dd, J1 14.8 Hz, J2 2.0 Hz, 1H), 4.03 (m, 1H),2.73 (d, J 4.4 Hz, 3H), 1.37 (d, J 7.2 Hz, 3H). Compound 42(104 mg, 0.456 mmol) was added to the solution of (R,S)-69, (R)-69or (S)-69 (100 mg, 0.416 mmol) in DMF (1 mL). The resultingmixture was stirred for 18 h at 80, then the solvent was removedunder reduced pressure and the product was subjected to HPLC toafford 28e37 mg (15e20%) of (R,S)-13, (R)-13 or (S)-13. (R,S)-13: MS(ESI) [MH] 451. 1H NMR (400 MHz, CDCl3) d 8.28 (t, J 8.6 Hz,1H), 8.01 (d, J 8.0 Hz, 1H), 7.94 (d, J 1.2 Hz, 1H), 7.81 (dd,J1 8.0 Hz, J2 1.2 Hz, 1H), 7.48 (dd, J1 12.4 Hz, J2 1.6 Hz, 1H),7.36 (dd, J1 8.4 Hz, J2 1.6 Hz, 1H), 6.72 (m, 1H), 4.83 (q, J 7.2 Hz,1H), 3.08 (d, J 4.8 Hz, 3H), 1.60 (d, J 7.2 Hz, 3H). ESIHRMS m/zcalcd for C20H15F4N4O2S [MH] 451.0846; found 451.0844.
  • 39
  • [ 1351185-56-2 ]
  • [ 1315053-78-1 ]
  • (R)-3-[3-fluoro-4-(methylcarbamoyl)phenylamino]tetrahydrofuran-3-carboxylic acid [ No CAS ]
  • C21H21F2N3O5 [ No CAS ]
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