Triethylamine → HCID 73058034, compound

HRID 2207336Notes

Reaction equation

HRID 2207336 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:9][C:10](=[O:19])[C:11]3[C:16]([CH:17]=2)=[CH:15][CH:14]=[C:13]([F:18])[CH:12]=3)=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH2:49]([OH:54])[CH2:50][CH2:51][CH:52]=[CH2:53].C([NH2+]C(C)C)(C)C.F[B-](F)(F)F.C(N(CC)CC)C.F[B-](F)(F)F.[H+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CCCCCCC.O1CCOCC1>[F:18][C:13]1[CH:12]=[C:11]2[C:16]([CH:17]=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([C:52]4([CH3:53])[CH2:51][CH2:50][CH2:49][O:54]4)=[CH:3][CH:4]=3)[NH:9][C:10]2=[O:19])=[CH:15][CH:14]=1

Participants

10

Reactant 6

HCID 8471Triethylamine2×HCID 131814-Penten-1-OLHCID 28118Tetrafluoroboric acidHCID 812191,3-Bis(diphenylphosphino)propaneHCID 24873878HCID 24873878, compoundHCID 90039988HCID 90039988, compound

Product 1

HCID 73058034HCID 73058034, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 8900HeptaneSolventHCID 312751,4-DioxaneSolvent

Procedure

3-(4-Bromo-phenyl)-7-fluoro-2H-isoquinolin-1-one (159 mg, 0.50 mmol), palladium(II)acetate (5.6 mg, 0.03 mmol), 1,3-bis-(diphenylphosphino)-propane (21.3 mg, 0.05 mmol), 4-pentene-1-ol (51.7 mg, 0.60 mmol) and diisopropylammonium-tetrafluoroborate (142 mg, 0.75 mmol) are weighed into a reaction vial. 1,4-Dioxane (1 ml) is added and the reaction vial is flushed with nitrogen. The resulting suspension is stirred for 1 minute, triethylamine (208 μl, 1.50 mmol) is added and the reaction vial is flushed with nitrogen and closed. The reaction mixture is stirred overnight at 110° C. The reaction mixture is allowed to cool to room temperature. n-Heptane (1.5 ml) and tetrafluoroboric acid (0.21 ml, 54% solution in diethylether, 1.5 mmol) are added and the resulting biphasic mixture is stirred vigorously at room temperature for 3 hours. Triethylamine (69 μl, 0.5 mmol) is added and the reaction mixture is then partitioned between water and dichloromethane. The organic phase is dried over sodium sulfate and evaporated. The residue is chromatographed on a silica gel column with cyclohexane/ethyl acetate as eluent to afford 7-fluoro-3-[4-(2-methyl-tetrahydro-furan-2-yl)-phenyl]-2H-isoquinolin-1-one as white powder; HPLC/MS 2.78 min. (B), [M+H] 324; 1H NMR (500 MHz, DMSO-d6) δ [ppm] 11.58 (s, 1H), 7.85 (dd, J=9.5, 2.8 Hz, 1H), 7.80 (dd, J=8.8, 5.3 Hz, 1H), 7.77-7.71 (m, 2H), 7.62 (td, J=8.7, 2.8 Hz, 1H), 7.53-7.46 (m, 2H), 6.95 (s, 1H), 3.94 (td, J=7.8, 6.4 Hz, 1H), 3.83 (td, J=8.0, 5.7 Hz, 1H), 2.11 (ddd, J=12.0, 8.0, 5.7 Hz, 1H), 2.04 (dt, J=11.9, 7.4 Hz, 1H), 1.97 (dtt, J=15.4, 7.7, 5.6 Hz, 1H), 1.74 (dqd, J=12.0, 7.6, 6.4 Hz, 1H), 1.46 (s, 3H).

Workup

  1. customthe reaction
  2. customvial is flushed with nitrogen
  3. customthe reaction
  4. customvial is flushed with nitrogen
  5. customclosed
  6. stirringThe reaction mixture is stirred overnight at 110° C
  7. stirringthe resulting biphasic mixture is stirred vigorously at room temperature for 3 hours
  8. customthe reaction mixture is then partitioned between water and dichloromethane
  9. dry with materialThe organic phase is dried over sodium sulfate
  10. customevaporated
  11. customThe residue is chromatographed on a silica gel column with cyclohexane/ethyl acetate as eluent

Sources & evidence

ORD record
ord-32c4373d3da54c04ab8ae7dcffc6b4fa
Source dataset
uspto-grants-2016_06
Patent number
US09376433B2

Reaction notes

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