Triethylamine → HCID 118353185, compound

HRID 1773996Notes

Reaction equation

HRID 1773996 reaction equation
[F:1][C:2]1[CH:11]=[C:10]([F:12])[C:9](O)=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2.CCN(CC)CC.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.[O-]S(C(F)(F)F)(=O)=O.[CH2:44]([O:46][C:47](=[O:66])[CH2:48][C:49]1[CH:54]=[CH:53][C:52]([O:55][CH3:56])=[C:51](B2OC(C)(C)C(C)(C)O2)[CH:50]=1)[CH3:45].C(=O)([O-])[O-].[Na+].[Na+]>C(Cl)Cl.C1(C)C=CC=CC=1.CCO.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:44]([O:46][C:47](=[O:66])[CH2:48][C:49]1[CH:54]=[CH:53][C:52]([O:55][CH3:56])=[C:51]([C:9]2[C:10]([F:12])=[CH:11][C:2]([F:1])=[C:3]3[C:8]=2[CH:7]=[N:6][CH:5]=[CH:4]3)[CH:50]=1)[CH3:45]

Participants

10

Reactant 6

HCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 67749Trifluoromethanesulfonic anhydrideHCID 2758875TrifluoromethanesulfonateHCID 58120060[4-Methoxy-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-acetic acid ethyl esterHCID 136602106HCID 136602106, compound

Product 1

HCID 118353185HCID 118353185, compound

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6344DichloromethaneSolvent2×HCID 86587398Ethanol toluene waterSolvent

Conditions

Temperature
0 °C

Procedure

To an ice-cooled suspension of 5,7-difluoro-isoquinolin-8-ol (200 mg, 1.10 mmol, 1.00 eq.) in DCM (10 mL), NEt3 (0.46 mL, 3.31 mmol, 3.00 eq.) and trifluoromethanesulfonic anhydride (0.29 mL, 1.66 mmol, 1.50 eq.) were added in sequence. The reaction mixture was stirred at 0° C. for 30 min and further at r.t. for 45 min. The mixture was diluted with DCM (20 mL) and washed with sat. aq. NaHCO3 soln. (2×10 mL). The org. layer was dried over MgSO4 and concentrated in vacuo. To a mixture under N2 of the resulting triflate, [4-methoxy-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-acetic acid ethyl ester (354 mg, 1.10 mmol, 1.00 eq.), and sodium carbonate (468 mg, 4.42 mmol, 4.00 eq.) in toluene/EtOH/water 20:4:1 (10 mL), tetrakis(triphenylphosphine) palladium (0) (64 mg, 0.06 mmol, 0.05 eq.) was added. The mixture was stirred at 100° C. for 18 hours. The mixture was allowed to cool to r.t. and concentrated in vacuo. The residue was taken up in DMF, filtered, and purified by prep. HPLC (column Atlantis, 30×75 mm, 10 um, UV/MS, acidic conditions) and concentrated in vacuo to give the title compound as a brown oil.

Workup

  1. additionwere added in sequence
  2. washwashed with sat. aq. NaHCO3 soln
  3. dry with materiallayer was dried over MgSO4
  4. concentrationconcentrated in vacuo
  5. stirringThe mixture was stirred at 100° C. for 18 hours
  6. temperatureto cool to r.t.
  7. concentrationconcentrated in vacuo
  8. filtrationfiltered
  9. custompurified by prep
  10. concentrationHPLC (column Atlantis, 30×75 mm, 10 um, UV/MS, acidic conditions) and concentrated in vacuo

Sources & evidence

ORD record
ord-e9873ae2a90a45a585c51b3312939c88
Source dataset
uspto-grants-2016_02
Patent number
US09255090B2

Reaction notes

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