Potassium Carbonate → 3-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo [1,2-b]pyrazol-3-yl)-pyrazolo[1,5-a]pyrimidine

HRID 751316Notes

Reaction equation

HRID 751316 reaction equation
Br[C:2]1[CH:3]=[N:4][N:5]2[CH:10]=[CH:9][CH:8]=[N:7][C:6]=12.[N:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[C:17]1[C:18](B(O)O)=[C:19]2[CH2:24][CH2:23][CH2:22][N:20]2[N:21]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+]>C(OCC)(=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].O1CCOCC1>[N:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[C:17]1[C:18]([C:2]2[CH:3]=[N:4][N:5]3[CH:10]=[CH:9][CH:8]=[N:7][C:6]=23)=[C:19]2[CH2:24][CH2:23][CH2:22][N:20]2[N:21]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 122032083-Bromopyrazolo(1,5-a)pyrimidineHCID 59710031(2-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-3-boronic acid

Product 1

HCID 104249963-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo [1,2-b]pyrazol-3-yl)-pyrazolo[1,5-a]pyrimidineYield 4.5%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

Weigh into a round bottom flask 3-bromopyrazolo[1,5-a]pyrimidine (Lynch et al. Can. J. Chem. 1975, 53, 119-122; 0.095 g, 0.48 mmol), 2-(pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-3-boronic acid (Preparation 5; 0.10 g, 0.44 mmol), triphenylphosphine (Aldrich; 0.007 g, 0.027 mmol) and tris(dibenzylideneacetone)dipalladium(0) (Aldrich; 0.015 g, 0.016 mmol). Add p-dioxane (6 ml) and 2.0M aqueous potassium carbonate (2 mL). Stir and reflux under nitrogen for 6 h. Dilute with ethyl acetate, separate the organic layer, concentrate under reduced pressure, and chromatograph on flash silica using neat acetonitrile. Purify on a preparative reverse phase C-18 high-performance chromatography column using a gradient from 5% to 100% acetonitrile in 0.03% aqueous hydrochloric acid. Concentrate the pure fractions under reduced pressure, dissolve the residue in distilled water, and make basic by adding 1.0M aqueous sodium hydroxide. Extract with dichloromethane, dry the organic layer over anhydrous sodium sulfate, filter, and concentrate under reduced pressure to obtain 6 mg (4.5%) of the title compound as a yellow solid. TOF MS ES+ exact mass calculated for C17H15N6 (M+1): m/z=303.1358; Found: 303.1371. 1H NMR (400 MHz, CDCl3) δ 8.66 (d, J=2 Hz, 1H), 8.64 (d, J=2 Hz, 1H), 8.41 (dd, J=4, 2 Hz, 1H), 8.31 (s, 1H), 7.70 (m, 2H), 7.21 (m, 1H), 6.79 (dd, J=7, 4 Hz, 1H), 4.30 (t, J=7 Hz, 2H), 3.10 (t, J=8 Hz, 2H), 2.68 (m, 2H).

Workup

  1. temperaturereflux under nitrogen for 6 h
  2. customseparate the organic layer
  3. concentrationconcentrate under reduced pressure, and chromatograph on flash silica using neat acetonitrile
  4. customPurify on a preparative reverse phase C-18 high-performance chromatography column
  5. concentrationConcentrate the pure fractions under reduced pressure
  6. dissolutiondissolve the residue in distilled water
  7. additionby adding 1.0M aqueous sodium hydroxide
  8. extractionExtract with dichloromethane
  9. dry with materialdry the organic layer over anhydrous sodium sulfate
  10. filtrationfilter
  11. concentrationconcentrate under reduced pressure

Sources & evidence

ORD record
ord-45d6634ef4cc47fd98a59d7dd60d893b
Source dataset
uspto-grants-2008_07
Patent number
US07405299B2

Reaction notes

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