Acetonitrile → HCID 57837456, compound

HRID 731742Notes

Reaction equation

HRID 731742 reaction equation
I[C:2]1[C:3]([CH:11]([CH3:13])[CH3:12])=[N:4][N:5]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=12.CC1(C)C(C)(C)OB([C:22]2[CH:23]=[N:24][N:25](C(OC(C)(C)C)=O)[CH:26]=2)O1.C(#N)C.C([O-])(O)=O.[Na+]>FC(F)(F)C(O)=O.ClCCl>[CH:11]([C:3]1[C:2]([C:22]2[CH:23]=[N:24][NH:25][CH:26]=2)=[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][N:5]2[N:4]=1)([CH3:13])[CH3:12]

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 516892Sodium BicarbonateHCID 16217654tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylateHCID 57837525HCID 57837525, compound

Product 1

HCID 57837456HCID 57837456, compoundYield 61.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 6422Trifluoroacetic acidSolvent

Procedure

To two 20 ml microwave reaction vials were each added 3-iodo-2-isopropyl-pyrazolo[1,5-a]pyridine (486 mg, 1.69 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-pyrazolecarboxylate (500 mg, 1.69 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (139 mg, 0.17 mmol), acetonitrile (8 ml), and 1 M aqueous NaHCO3 solution (5 ml). The mixture was placed in a microwave reactor for 2 hours at 140° C. The reaction mixture from the two vials were combined and concentrated in vacuo, and the crude material was partitioned between dichloromethane and water. The organic layer was separated, dried over sodium sulfate, filtered, and concentrated in vacuo. The crude material was purified by silica gel flash chromatography (0 to 50% ethyl acetate in hexanes) to give the protected-analog. The protected analog was dissolved in 20% trifluoroacetic acid in dichloromethane (50 ml) and stirred at room temperature. The reaction was monitored by HPLC for completion (2 hours). The mixture was concentrated in vacuo, and the concentrated material was dissolved in 4N hydrochloric acid in dioxane. Ether was added to the acidic solution to precipitate out the desired material. The material was filtered and dried in vacuo under high vacuum to give 235 mg (31%) of 2-isopropyl-3-(1H-pyrazol-4-yl)-pyrazolo[1,5-a]pyridine as the hydrochloric acid salt. 1H-NMR (250 MHz, DMSO-d6) δ 8.70 (broad s, 1H), 8.64 (d, J=7.0 Hz, 2H), 8.07 (s, 1H), 7.61 (d, J=9.0 Hz, 1H), 7.19 (dd, J=7.8, 6.8 Hz, 1H), 6.85 (t, J=6.8 Hz, 1H), 3.30 (sept, J=7.0 Hz, 1H), 1.29 (d, J=6.8 Hz, 6H); LC/MS 227.1 m/z (M+H+). Compound 1104.

Workup

  1. concentrationconcentrated in vacuo
  2. customthe crude material was partitioned between dichloromethane and water
  3. customThe organic layer was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified by silica gel flash chromatography (0 to 50% ethyl acetate in hexanes)
  8. customto give the protected-analog
  9. customwas monitored by HPLC for completion (2 hours)
  10. concentrationThe mixture was concentrated in vacuo
  11. dissolutionthe concentrated material was dissolved in 4N hydrochloric acid in dioxane
  12. additionEther was added to the acidic solution
  13. customto precipitate out the desired material
  14. filtrationThe material was filtered
  15. customdried in vacuo under high vacuum

Sources & evidence

ORD record
ord-a1c72aa487e64298aec6d3b45a23a554
Source dataset
uspto-grants-2009_09
Patent number
US07585875B2

Reaction notes

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