Methanol → HCID 66766276, compound

HRID 341298Notes

Reaction equation

HRID 341298 reaction equation
Br[CH2:2][C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9]1[N:14]=[C:15](Cl)[CH:16]=[CH:17][C:8]2=1)=O.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH3:27][OH:28]>CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:27][O:28][C:8]1[CH:17]=[CH:16][C:3]([C:5]2[CH:6]=[C:7]3[C:11](=[CH:12][CH:13]=2)[NH:10][C:9]2[N:14]=[CH:15][C:16]([CH:2]=[CH:3][C:5]4[CH:13]=[CH:12][CH:11]=[CH:7][CH:6]=4)=[CH:17][C:8]3=2)=[CH:2][CH:9]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 62657Potassium Phosphate, TribasicHCID 46185151HCID 46185151, compound

Product 1

HCID 66766276HCID 66766276, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

In sealed pressure tube and stir bar was charged Pd(OAc)2 (5 mg, 0.08 equiv.), 2-dicyclohexylphosphino-2′,6′-dimethoxyphenyl 1 (18 mg, 0.16 equiv.), a-carbolines (83 mg, 0.267 mmol), trans vinyl phenyl boronic acid (119 mg, 3.0 equiv.) and K3PO4 (142 mg, 2.5 equiv.). The tube was evacuated and back-filled with argon (this was repeated three additional times). 700 μl of anhydrous 1,4-dioxane was added (when degassed solvent was used) and the reaction mixture was allowed to stir at 100° C. overnight. After cooling to room temperature, the products were extracted from the water layer with ethyl acetate, dried over MgSO4, filtered through celite and solvents were removed under reduced pressure. The crude product was purified by flash chromatography (CH2Cl2/EtOAc 9:1) to afford R315 in 65% yield as a white solid; mp>220° C. (MeOH); IR: 3060, 2994, 2833, 1606, 1517, 1485, 1460, 1232, 957, 813, 740, 692 cm−1; 1H-NMR (300 MHz, DMSO-d6): δ 11.86 (bs, 1H), 8.95 (d, 1H, J=2.1 Hz), 8.61 (d, 1H, J=2.1 Hz), 8.47 (d, 1H, J=1.3 Hz), 7.74 (dd, 1H, J=1.9, 8.5 Hz), 7.71 (d, 214, J=8.9 Hz), 7.63 (d, 2H, J=7.1 Hz), 7.54 (d, 1H, J=8.5 Hz), 7.46 (d, 1H, J=16.4 Hz), 7.43-7.39 (m, 2H), 7.37 (d, 1H, J=16.4 Hz), 7.27 (t, 1H, J=7.4 Hz), 7.07 (d, 2H, J=8.9 Hz), 3.82 (s, 3H); 13C-NMR (75 MHz, DMSO-d6): δ 158.4 (C), 152.0 (C), 146.5 (CH), 138.5 (C), 137.4 (C), 133.4 (C), 131.9 (C), 128.8 (2 CH), 127.7 (2 CH), 127.4 (CH), 126.8 (CH), 126.3 (CH), 126.2 (2 CH), 125.6 (CH), 124.9 (CH), 127.8 (C), 121.1 (C), 118.9 (CH), 115.8 (C), 114.4 (2 CH), 111.7 (CH), 55.2 (CH3); MS (ESI) m/z 377.3 [M+H+]; HRMS (ESI): Calcd for C26H20N2O: 377.1654. Found: 377.1653.

Workup

  1. customThe tube was evacuated
  2. additionback-filled with argon (
  3. addition700 μl of anhydrous 1,4-dioxane was added
  4. custom(when degassed solvent was used)
  5. stirringto stir at 100° C. overnight
  6. extractionthe products were extracted from the water layer with ethyl acetate
  7. dry with materialdried over MgSO4
  8. filtrationfiltered through celite and solvents
  9. customwere removed under reduced pressure
  10. customThe crude product was purified by flash chromatography (CH2Cl2/EtOAc 9:1)
  11. customto afford R315 in 65% yield as a white solid

Sources & evidence

ORD record
ord-c8e81c752d304783bcf46c32dc099243
Source dataset
uspto-grants-2014_11
Patent number
US08895744B2

Reaction notes

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