Triethylamine → HCID 58404636, compound

HRID 1253548Notes

Reaction equation

HRID 1253548 reaction equation
I[C:2]1[CH:3]=[N:4][N:5]2[CH:10]=[C:9]([C:11]3[CH:12]=[N:13][N:14]([CH3:16])[CH:15]=3)[CH:8]=[C:7]([O:17][CH2:18][C:19]3[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=3)[C:6]=12.C(N(CC)CC)C.[CH:32]1([C:35]#[CH:36])[CH2:34][CH2:33]1>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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].[Cu]I>[CH:32]1([C:35]#[C:36][C:2]2[CH:3]=[N:4][N:5]3[CH:10]=[C:9]([C:11]4[CH:12]=[N:13][N:14]([CH3:16])[CH:15]=4)[CH:8]=[C:7]([O:17][CH2:18][C:19]4[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=4)[C:6]=23)[CH2:34][CH2:33]1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 138823CyclopropylacetyleneHCID 67374988HCID 67374988, compound

Product 1

HCID 58404636HCID 58404636, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Procedure

3-iodo-6-(1-methyl-1H-pyrazol-4-yl)-4-(pyridin-3-ylmethoxy)pyrazolo[1,5-a]pyridine from Step 2 (11.0 mg, 0.026 mmol), tetrakis(triphenylphosphine)palladium (0) (3.0 mg, 2.6 μmol), and CuI (2.9 mg, 0.02 mmol) were suspended in DMF (1 ml). Triethylamine (11 μl, 0.08 mmol) and cyclopropyl acetylene (5.1 mg, 0.08 mmol) were added and the mixture was sparged with argon for 10 minutes. After stirring at ambient temperature for 1.5 h, the reaction mixture was diluted in ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate and brine then dried over sodium sulfate, filtered and concentrated. The residue was 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 to afford 3-(cyclopropylethynyl)-6-(1-methyl-1H-pyrazol-4-yl)-4-(pyridin-3-ylmethoxy)pyrazolo[1,5-a]pyridine. 1H NMR (500 MHz, DMSO-d6) δ 8.79 (s, 1H); 8.65 (s, 1H); 8.57-8.60 (m, 1H); 8.30 (s, 1H); 8.00-8.05 (m, 2H); 7.98 (s, 1H); 7.49 (dd, 1H); 7.12 (s, 1H); 5.37 (s, 2H); 3.87 (s, 3H), 1.39-1.45 (m, 1H); 0.71-0.76 (m, 2H); 0.42-0.46 (m, 2H). LRMS (ESI) calculated for C22H20N5O [M+H]+, 370.2; found 370.0.

Workup

  1. customthe mixture was sparged with argon for 10 minutes
  2. additionthe reaction mixture was diluted in ethyl acetate
  3. washwashed with saturated aqueous sodium hydrogen carbonate and brine
  4. dry with materialthen dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by preparative HPLC Reverse phase (C-18)
  8. washeluting with Acetonitrile/Water+0.05% TFA
  9. additionThe fractions containing product
  10. additiondiluted in ethyl acetate
  11. washwashed with aqueous sodium bicarbonate
  12. dry with materialdried over sodium sulfate
  13. filtrationThe solution was filtered
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-52adca9af0194547b7321724b40ac4d1
Source dataset
uspto-grants-2013_06
Patent number
US08455477B2

Reaction notes

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