Triethylamine → HCID 58404807, compound

HRID 1253549Notes

Reaction equation

HRID 1253549 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[C:9]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=3)[C:10]3[N:11]([N:13]=[CH:14][CH:15]=3)[CH:12]=2)[CH:4]=[N:3]1.IN1C(=O)CCC1=O.[I-].C(N(CC)CC)C.[CH:40]1([C:43]#[CH:44])[CH2:42][CH2:41]1>CN(C=O)C.[Cu]I.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]>[CH:40]1([C:43]#[C:44][C:15]2[CH:14]=[N:13][N:11]3[CH:12]=[C:7]([C:5]4[CH:4]=[N:3][N:2]([CH3:1])[CH:6]=4)[CH:8]=[C:9]([O:16][CH2:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=4)[C:10]=23)[CH2:42][CH2:41]1

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 30165Iodide IonHCID 120273N-IodosuccinimideHCID 138823CyclopropylacetyleneHCID 58404918HCID 58404918, compound

Product 1

HCID 58404807HCID 58404807, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent2×

Procedure

6-(1-methyl-1H-pyrazol-4-yl)-4-(pyridin-2-ylmethoxy)pyrazolo[1,5-a]pyridine (10.0 mg, 0.033 mmol) and N-iodosuccinimide (8.8 mg, 0.04 mmol) were dissolved in DMF (1 ml). After 20 minutes, LCMS analysis indicated complete conversion to the iodide. At this time, copper (I) iodide (3.7 mg, 0.02 mmol), tetrakis(triphenylphosphine)palladium (0) (3.8 mg, 3.2 μmol), triethylamine (0.014 ml, 0.098 mmol), and cyclopropylacetylene (6.5 mg, 0.10 mmol) was added, followed by 0.5 mL of DMF to wash down the sides of the flask. The mixture was sparged with argon for 10 minutes then allowed to stir at ambient temperature overnight. 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-2-ylmethoxy)pyrazolo[1,5-a]pyridine. 1H NMR (500 MHz, DMSO-d6) δ 8.66 (s, 1H); 8.61 (d, 1H); 8.33 (s, 1H); 8.05 (s, 1H); 8.01 (s, 1H); 7.88-7.95 (m, 2H); 7.36-7.40 (m, 1H); 7.15 (s, 1H); 5.38 (s, 2H); 3.86 (s, 3H), 1.51-1.58 (m, 1H); 0.81-0.88 (m, 2H); 0.56-0.60 (m, 2H). LRMS (ESI) calculated for C22H20N5O [M+H]+, 370.2; found 370.1.

Workup

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

Sources & evidence

ORD record
ord-6efb42b584fe4b7a9a96747cd73e9ffc
Source dataset
uspto-grants-2013_06
Patent number
US08455477B2

Reaction notes

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