Trifluoromethanesulfonic anhydride → HCID 90341039, compound

HRID 595772Notes

Reaction equation

HRID 595772 reaction equation
[F:1][C:2]1[C:3]2[CH:4]=[C:5]3[C:14]4[N:13]=[C:12]([C:15]5[C:16]([N:35]([CH3:40])[S:36]([CH3:39])(=[O:38])=[O:37])=[CH:17][C:18]6[O:22][C:21]([C:23]7[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=7)=[C:20]([C:30]([NH:32][CH3:33])=[O:31])[C:19]=6[CH:34]=5)[CH:11]=[CH:10][C:9]=4[CH2:8][CH:7]([CH2:41]O)[N:6]3[C:43]=2[CH:44]=[CH:45][CH:46]=1.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.C(N(CC)C(C)C)(C)C.Cl.[F:72][CH:73]1[CH2:76][NH:75][CH2:74]1>C(Cl)Cl.O>[F:1][C:2]1[C:3]2[CH:4]=[C:5]3[C:14]4[N:13]=[C:12]([C:15]5[C:16]([N:35]([CH3:40])[S:36]([CH3:39])(=[O:37])=[O:38])=[CH:17][C:18]6[O:22][C:21]([C:23]7[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=7)=[C:20]([C:30]([NH:32][CH3:33])=[O:31])[C:19]=6[CH:34]=5)[CH:11]=[CH:10][C:9]=4[CH2:8][CH:7]([CH2:41][N:75]4[CH2:76][CH:73]([F:72])[CH2:74]4)[N:6]3[C:43]=2[CH:44]=[CH:45][CH:46]=1

Participants

7

Reactant 4

HCID 67749Trifluoromethanesulfonic anhydrideHCID 81531DiisopropylethylamineHCID 101250543-fluoroazetidine HydrochlorideHCID 90341018HCID 90341018, compound

Product 1

HCID 90341039HCID 90341039, compoundYield 21.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 5-(11-fluoro-6-(hydroxymethyl)-5,6-dihydroindolo[1,2-h][1,7]naphthyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (180 mg, 0.280 mmol) in DCM (8 mL) at 0° C. was added trifluoromethanesulfonic anhydride in DCM (0.560 mL, 0.560 mmol). The mixture was stirred at 0° C. for 2 h, then at RT for 1 h. The mixture was evaporated in vacuo to remove the volatiles, redissolved in DMF (8 mL), followed by addition of N,N-diisopropyl ethylamine (362 mg, 2.80 mmol) and 3-fluoroazetidine hydrochloride (125 mg, 1.120 mmol). The mixture was heated to 60° C. and stirred for 3 h. 20 ml H2O was added and the mixture stirred for 10 min. Filtration collected the yellow solid. After washing with additional H2O, the yellow solid was purified by chromatography, and eluted with 0-70% ethyl acetate in hexane to gave 5-(11-fluoro-6-((3-fluoroazetidin-1-yl)methyl)-5,6-dihydroindolo[1,2-h][1,7]naphthyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (42 mg, yield: 21%). MS (M+H)+: 700.

Workup

  1. waitat RT for 1 h
  2. customThe mixture was evaporated in vacuo
  3. customto remove the volatiles
  4. dissolutionredissolved in DMF (8 mL)
  5. temperatureThe mixture was heated to 60° C.
  6. stirringstirred for 3 h
  7. stirringthe mixture stirred for 10 min
  8. filtrationFiltration
  9. customcollected the yellow solid
  10. washAfter washing with additional H2O
  11. customthe yellow solid was purified by chromatography
  12. washeluted with 0-70% ethyl acetate in hexane

Sources & evidence

ORD record
ord-065c86ee525d4791935a9ed9c232a815
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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