Dimethylformamide → HCID 86657058, compound

HRID 1253567Notes

Reaction equation

HRID 1253567 reaction equation
C(O[C:9]1[N:14]2[C:15](I)=[CH:16][N:17]=[C:13]2[CH:12]=[C:11]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:10]=1)C1C=CC=CC=1.C(N(CC)CC)C.[C:32]([C:34]1[CH:35]=[N:36][CH:37]=[CH:38][CH:39]=1)#[CH:33].CN([CH:43]=[O:44])C>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[CH3:43][O:44][C:16]1[N:17]=[C:13]2[CH:12]=[C:11]([C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:10]=[CH:9][N:14]2[C:15]=1[C:33]#[C:32][C:34]1[CH:35]=[N:36][CH:37]=[CH:38][CH:39]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 1860033-EthynylpyridineHCID 58404694HCID 58404694, compound

Product 1

HCID 86657058HCID 86657058, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Procedure

5-(benzyloxy)-3-iodo-7-phenylimidazo[1,2-a]pyridine (32.0 mg, 0.091 mmol), tetrakis(triphenylphosphine)palladium(0) (10.6 mg, 9.14 μmol) and copper(I)iodide (10.44 mg, 0.055 mmol) were suspended in DMF (1 mL). Triethylamine (0.025 mL, 0.183 mmol) and 3-ethynylpyridine (28.3 mg, 0.274 mmol) were added, and the mixture was sparged with argon for 5 minutes. The reaction was stirred at room temperature for 1 hour, diluted with acetonitrile, DMSO and water. The solution was directly purified by preparative HPLC Reverse phase (C-18), eluting with acetonitrile/water+0.05% TFA. The fractions containing product were combined and diluted in ethyl acetate, then washed with aqueous sodium bicarbonate and dried over sodium sulfate. The solution was filtered and concentrated under reduced pressure to afford impure material, which was additionally purified by column chromatography on silica gel (methanol/dichloromethane gradient) to afford -methoxy-7-phenyl-3-(pyridin-3-ylethynyl)imidazo[1,2-a]pyridine. 1H NMR (500 MHz, CDCl3) δ 8.75 (d, 1H), 8.53 (dd, 1H), 7.89 (s, 1H), 7.75-7.79 (m, 1H), 7.62-7.67 (m, 2H), 7.53 (s, 1H), 7.45-7.50 (m, 2H), 7.39-7.43 (m, 1H), 7.27-7.31 (m, 1H), 6.37 (s, 1H), 4.16 (s, 3H). LRMS (ESI) calculated for C21H16N3O [M+H]+, 326.1; found 326.0.

Workup

  1. customthe mixture was sparged with argon for 5 minutes
  2. additiondiluted with acetonitrile, DMSO and water
  3. customThe solution was directly purified by preparative HPLC Reverse phase (C-18)
  4. washeluting with acetonitrile/water+0.05% TFA
  5. additionThe fractions containing product
  6. additiondiluted in ethyl acetate
  7. washwashed with aqueous sodium bicarbonate
  8. dry with materialdried over sodium sulfate
  9. filtrationThe solution was filtered
  10. concentrationconcentrated under reduced pressure
  11. customto afford impure material, which
  12. customwas additionally purified by column chromatography on silica gel (methanol/dichloromethane gradient)

Sources & evidence

ORD record
ord-4922463f07834f1492a324523c91fb00
Source dataset
uspto-grants-2013_06
Patent number
US08455477B2

Reaction notes

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