Potassium Carbonate → HCID 59452210, compound

HRID 2381153Notes

Reaction equation

HRID 2381153 reaction equation
[CH3:1][C:2]1([CH3:30])[O:6][C@@H:5]([CH2:7][O:8][NH:9][C:10]([C:12]2[N:20]([CH2:21][C:22]3[CH:27]=[CH:26][C:25](I)=[CH:24][C:23]=3[F:29])[C:15]3=[CH:16][N:17]=[CH:18][CH:19]=[C:14]3[CH:13]=2)=[O:11])[CH2:4][O:3]1.C[Si]([C:35]#[CH:36])(C)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+]>N1CCCCC1.C(OCC)(=O)C.CO.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:1][C:2]1([CH3:30])[O:6][C@@H:5]([CH2:7][O:8][NH:9][C:10]([C:12]2[N:20]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([C:35]#[CH:36])=[CH:24][C:23]=3[F:29])[C:15]3=[CH:16][N:17]=[CH:18][CH:19]=[C:14]3[CH:13]=2)=[O:11])[CH2:4][O:3]1

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 66111TrimethylsilylacetyleneHCID 59452214HCID 59452214, compound

Product 1

HCID 59452210HCID 59452210, compoundYield 68%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 887MethanolSolventHCID 8082PiperidineSolventHCID 8857Ethyl AcetateSolvent

Procedure

Palladium (II) acetate (1.5 mg, 5 μmol) was added to a mixture of 1-(2-fluoro-4-iodo-benzyl)-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid ((R)-2,2-dimethyl-[1,3]-dioxolan-4-ylmethoxy)-amide (55 mg, 0.11 mmol), trimethylsilylacetylene (138 μl, 1.0 mmol) and triphenylphosphine (3 mg, 10 μmol) in piperidine (0.5 ml). The resultant mixture was heated at 150° C. under microwave irradiation for 10 seconds. The reaction mixture was diluted with ethyl acetate (35 ml) and washed sequentially with water (10 ml), then brine (10 ml). The organic layer was isolated, dried over magnesium sulphate and concentrated in vacuo to provide a residue. The residue was dissolved in methanol (5 ml) to which potassium carbonate (29 mg, 0.21 mmol) was added, and the resultant suspension was stirred at room temperature for 2 hours. The reaction mixture was filtered, concentrated in vacuo, and then partitioned between ethyl acetate (25 ml) and water (20 ml). The organic layer was isolated, dried over magnesium sulphate and concentrated in vacuo to provide a residue. Purification by flash chromatography (Si-SPE, dichloromethane:ethyl acetate, 100:0 to 70:30 to 40:60 to 0:100) afforded the title compound as a yellow solid (30 mg, 68%). LCMS (method B): RT=2.21 min, (M−H)−=422, (M+H)+=424.

Workup

  1. washwashed sequentially with water (10 ml)
  2. customThe organic layer was isolated
  3. dry with materialdried over magnesium sulphate
  4. concentrationconcentrated in vacuo
  5. customto provide a residue
  6. additionwas added
  7. filtrationThe reaction mixture was filtered
  8. concentrationconcentrated in vacuo
  9. custompartitioned between ethyl acetate (25 ml) and water (20 ml)
  10. customThe organic layer was isolated
  11. dry with materialdried over magnesium sulphate
  12. concentrationconcentrated in vacuo
  13. customto provide a residue
  14. customPurification by flash chromatography (Si-SPE, dichloromethane:ethyl acetate, 100:0 to 70:30 to 40:60 to 0:100)

Sources & evidence

ORD record
ord-3afc997807bc4bb79d4463f6f71c163e
Source dataset
uspto-grants-2012_09
Patent number
US08258152B2

Reaction notes

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