Triphenylphosphine → HCID 10024407, compound

HRID 1765105Notes

Reaction equation

HRID 1765105 reaction equation
[F:1][C:2]1[C:3]2[N:4]([CH:12]=[CH:13][N:14]=2)[CH:5]=[CH:6][C:7]=1[C:8]([OH:11])([CH3:10])[CH3:9].Cl[C:16]1[N:21]=[C:20]([C:22]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:23]=2[C:24]#[N:25])[C:19]([F:31])=[CH:18][CH:17]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C([O-])(=O)C.[K+]>CN(C)C(=O)C.CO.C(O)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:30][C:27]1[CH:28]=[CH:29][C:22]([C:20]2[C:19]([F:31])=[CH:18][CH:17]=[C:16]([C:12]3[N:4]4[CH:5]=[CH:6][C:7]([C:8]([OH:11])([CH3:10])[CH3:9])=[C:2]([F:1])[C:3]4=[N:14][CH:13]=3)[N:21]=2)=[C:23]([CH:26]=1)[C:24]#[N:25]

Participants

9

Reactant 4

HCID 11776TriphenylphosphineHCID 517044Potassium AcetateHCID 17975608HCID 17975608, compoundHCID 444087292-(8-Fluoroimidazo[1,2-a]pyridin-7-yl)propan-2-ol

Product 1

HCID 10024407HCID 10024407, compound

Reagents, catalysts & solvents 4

HCID 176Acetic AcidCatalystHCID 167845palladium(II) acetateCatalystHCID 887MethanolSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
130 °C

Procedure

To 2-(8-fluoroimidazo[1,2-α]pyridin-7-yl)propan-2-ol (0.21 g, 1.10 mmol), 2-(6-chloro-3-fluoropyridin-2-yl)-5-fluorobenzonitrile (0.25 g, 1.00 mmol) and palladium acetate (0.011 g, 0.05 mmol) in N,N-dimethylacetamide (2 ml) was added triphenylphosphine (0.013 g, 0.05 mmol) followed by potassium acetate (0.14 g, 1.51 mmol) and the mixture heated at 130° C. for 2 h. The reaction was cooled to ambient temperature, diluted with methanol (8 ml) and 2 drops of acetic acid were added. The mixture was poured onto a strong cation exchange cartridge and eluted with several column lengths of methanol. Several column lengths of 2N ammonia in methanol were then eluted to recover the product. The pale yellow oil was chromatographed on silica, eluting with 3% methanol in dichloromethane, to give the title material as a white powdery solid. Recrystallised from ethyl acetate/ether to afford the title compound (215 mg): δH (400 MHz, CDCl3) 1.73 (6H, s), 2.07 (1H, s), 7.26 (1H, d, J 14.4), 7.45-7.49 (1H, m), 7.61 (1H, dd, J 2.6, 7.9), 7.67 (1H, t, J 9.0), 7.77-7.80 (1H, m), 7.88 (1H, dd, J 3.3, 8.9), 8.15 (1H, s), 9.59 (1H, d, J 7.3); m/z (ES+) 409.

Workup

  1. temperatureThe reaction was cooled to ambient temperature
  2. additionwere added
  3. additionThe mixture was poured onto a strong cation exchange cartridge
  4. washeluted with several column lengths of methanol
  5. washSeveral column lengths of 2N ammonia in methanol were then eluted
  6. customto recover the product
  7. customThe pale yellow oil was chromatographed on silica
  8. washeluting with 3% methanol in dichloromethane

Sources & evidence

ORD record
ord-9d3be35e0c7e4e3d8cf046733a084700
Source dataset
uspto-grants-2007_06
Patent number
US07226926B2

Reaction notes

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