Cesium carbonate → HCID 68795331, compound

HRID 1632059Notes

Reaction equation

HRID 1632059 reaction equation
[N:1]1([CH2:10][C:11]2[CH:12]=[CH:13][C:14]([O:26][CH3:27])=[C:15]([C:17]3[CH:18]=[CH:19][C:20]4[C:21]([CH:25]=3)=[N:22][O:23]N=4)[CH:16]=2)[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.BrC1C=C(C=CC=1[O:45]C)CN1C2C=CC=CC=2N=C1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O1C2C=CC(B(O)O)=CC=2OC1>CN(C=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].C(OCC)(=O)C>[CH3:27][O:26][C:14]1[C:15]([C:17]2[CH:18]=[CH:19][CH:20]=[C:21]([N+:22]([O-:23])=[O:45])[CH:25]=2)=[CH:16][C:11]([CH2:10][N:1]2[C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[N:3]=[CH:2]2)=[CH:12][CH:13]=1

Participants

9

Reactant 5

HCID 10796Cesium carbonateHCID 11776TriphenylphosphineHCID 2734371(2H-1,3-benzodioxol-5-yl)boronic acidHCID 60673465HCID 60673465, compoundHCID 68796110HCID 68796110, compound

Product 1

HCID 68795331HCID 68795331, compound

Reagents, catalysts & solvents 3

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Synthesis 5-(5-Benzoimidazol-1-ylmethyl-2-methoxy-phenyl)-benzo[1,2,5]oxadiazole (P-014). A suspension of 1-(3-Bromo-4-methoxy-benzyl)-1H-benzoimidazole (I-107, X═N) (250 mg, 0.778 mmol), 1 N aqueous cesium carbonate (2.4 mL), and triphenylphosphine (20.7 mg, 0.0788 mmol) in DMF (5 mL) was stirred. To the suspension was added benzo[1,3]dioxol-5-yl-boronic acid (155 mg, 0.946 mmol), the reaction purged with nitrogen, and bis(dibenzylideneacetone)palladium(0) (22.7 mg, 0.0394 mmol) was added under nitrogen. The reaction was stirred at 100° C. overnight. After cooling to room temperature, ethyl acetate (50 mL) was added. The organic suspension was washed with saturated aqueous ammonium chloride (2×50 mL), 1 N aqueous sodium hydroxide (3×50 mL), water (50 mL), and brine (50 mL), decolorized over activated carbon, dried over sodium sulfate, and removed under vacuum to give crude product. The product was purified by flash silica gel column chromatography eluting with 1% methanol in dichloromethane to give P-014 (102.1 mg, 36% yield) as an off white powder. 1H NMR (400 MHz, d6-DMSO) d: 8.446 (s, 1H), 8.054-8.020 (m, 2H), 7.715 (dd, J=9.60 Hz, 1.60 Hz, 1H), 7.651-7.649 (m, 2H), 7.605 (d, J=2.40 Hz, 1H), 7.440 (dd, J=8.60 Hz, 2.20 Hz, 1H), 7.244-7.147 (m, 3H), 5.485 (s, 2H), 3.787 (s, 3H).

Workup

  1. additionwas added under nitrogen
  2. stirringThe reaction was stirred at 100° C. overnight
  3. washThe organic suspension was washed with saturated aqueous ammonium chloride (2×50 mL), 1 N aqueous sodium hydroxide (3×50 mL), water (50 mL), and brine (50 mL)
  4. dry with materialdried over sodium sulfate
  5. customremoved under vacuum
  6. customto give crude product
  7. customThe product was purified by flash silica gel column chromatography
  8. washeluting with 1% methanol in dichloromethane
  9. customto give P-014 (102.1 mg, 36% yield) as an off white powder

Sources & evidence

ORD record
ord-ee59ba9df9d8426d9db4f86c8d63e50d
Source dataset
uspto-grants-2014_07
Patent number
US08791267B2

Reaction notes

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