Triethylamine → HCID 59375392, compound

HRID 2192982Notes

Reaction equation

HRID 2192982 reaction equation
[Br:1][C:2]1[CH:24]=[CH:23][C:5]2[C:6]([NH:16][CH:17]([CH3:22])[C:18]([CH3:21])([CH3:20])[CH3:19])=[N:7][C:8]3[C:9](I)=[CH:10][NH:11][C:12](=[O:14])[C:13]=3[C:4]=2[CH:3]=1.CC1(C)C2C=[CH:37][CH:36]=[C:35](P(C3C=CC=CC=3)C3C=CC=CC=3)[C:34]=2[O:33]C2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C(N(CC)CC)C>[Pd](Cl)Cl.C(O)CCC>[Br:1][C:2]1[CH:24]=[CH:23][C:5]2[C:6]([NH:16][CH:17]([CH3:22])[C:18]([CH3:21])([CH3:20])[CH3:19])=[N:7][C:8]3[C:9]([CH:34]([CH:35]4[CH2:37][CH2:36]4)[OH:33])=[CH:10][NH:11][C:12](=[O:14])[C:13]=3[C:4]=2[CH:3]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 59375664HCID 59375664, compound

Product 1

HCID 59375392HCID 59375392, compound

Reagents, catalysts & solvents 2

HCID 24290Palladium ChlorideCatalystHCID 2631-ButanolSolvent

Conditions

Temperature
100 °C

Procedure

9-bromo-4-iodo-6-[(1,2,2-trimethylpropyl)amino]benzo[c]-1,6-naphthyridin-1(2H)-one (50 mg, 0.100 mmol), palladium(II) chloride (0.355 mg, 1.999 μmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (1.157 mg, 1.999 μmol), triethylamine (18.11 μl, 0.130 mmol) and 1-butanol (1000 μl) were combined in a 40 mL vial and sparged with nitrogen for 5 minutes. The cap on the vial was removed and the atmosphere changed to carbon monoxide by pressurizing to 30 psi and releasing the pressure 3 times inside a stainless steel pressure vessel. Then, the pressure of CO was adjusted to 100 psi and heated to 100° C. for 5 h. Then, the reaction was cooled to room temperature, the reaction was then poured into ethyl acetate, washed with saturated NaHCO3, brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by preparative HPLC Reverse phase (C-18), eluting with Acetonitrile/Water+0.05% TFA, to afford the title compound as a white solid. 1H NMR (500 MHz, C2D6SO) δ 11.68 (d, 1H, J=6.0 Hz), 10.04 (d, 1H, J=2.0 Hz), 8.50 (d, 1H, J=9.0 Hz), 7.83 (d, 1H, J=7.0 Hz), 7.78 (d, 1H, J=7.5 Hz), 7.68 (d, 1H, J=8.5 Hz), 4.81 (m, 1H), 4.22 (m, 2H), 1.68 (m, 2H), 1.37 (m, 2H), 1.17 (m, 6H), 0.93 (s, 9H). LRMS (ESI) calc'd for (C23H29BrN3O3) [M+H]+ 476.1; found 476.1.

Workup

  1. customsparged with nitrogen for 5 minutes
  2. customThe cap on the vial
  3. customwas removed
  4. temperatureThen, the reaction was cooled to room temperature
  5. additionthe reaction was then poured into ethyl acetate
  6. washwashed with saturated NaHCO3, brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by preparative HPLC Reverse phase (C-18)
  11. washeluting with Acetonitrile/Water+0.05% TFA

Sources & evidence

ORD record
ord-f1a57dc54b2849cc801974a221930241
Source dataset
uspto-grants-2012_12
Patent number
US08329722B2

Reaction notes

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