Potassium Carbonate → 2-(benzyloxy)-5-(6-cyclopropylpyridin-2-yl)-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one

HRID 1396508Notes

Reaction equation

HRID 1396508 reaction equation
[CH2:1]([O:8][C:9]1[CH:25]=[C:12]2[C:13](=[O:24])[N:14]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19](Br)[N:18]=3)[CH2:15][CH2:16][N:11]2[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:26]1(B(O)O)[CH2:28][CH2:27]1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.CN(C=O)C.O.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>[CH2:1]([O:8][C:9]1[CH:25]=[C:12]2[C:13](=[O:24])[N:14]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([CH:26]4[CH2:28][CH2:27]4)[N:18]=3)[CH2:15][CH2:16][N:11]2[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 2760897Cyclopropylboronic acidHCID 867065172-(benzyloxy)-5-(6-bromopyridin-2-yl)-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one

Product 1

HCID 727147852-(benzyloxy)-5-(6-cyclopropylpyridin-2-yl)-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-oneYield 45.5%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

Tetrakis(triphenylphosphine)palladium (0) (14.5 mg, 0.013 mmol) was added to a stirred suspension of 2-(benzyloxy)-5-(6-bromopyridin-2-yl)-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one (0.1 g, 0.25 mmol), cyclopropylboronic acid (0.043 g, 0.5 mmol) and K2CO3 (0.104 g, 0.013 mmol) in a mixture of 1,4-dioxane (1 mL) and DMF (1 mL). The mixture was stirred at 150° C. for 15 minutes under microwave irradiation. The mixture was diluted with water and extracted with AcOEt. The organic layer was separated, washed with a saturated solution of NaCl, dried (Na2SO4), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 20/80). The desired fractions were collected, the solvents evaporated in vacuo and the residue triturated with DIPE to yield 2-(benzyloxy)-5-(6-cyclopropylpyridin-2-yl)-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one (41 mg, 45% yield) as a pale yellow solid. C21H20N4O2. 1H NMR (500 MHz, CDCl3) δ ppm 0.92-1.03 (m, 4H), 1.97-2.05 (m, 1H), 4.31 (dd, J=6.6, 5.2 Hz, 2H), 4.50 (dd, J=6.9, 5.2 Hz, 2H), 5.23 (s, 2H), 6.37 (s, 1H), 6.99 (d, J=6.9 Hz, 1H), 7.31-7.36 (m, 1H), 7.36-7.42 (m, 2H), 7.46 (d, J=7.2 Hz, 2H), 7.57 (t, J=7.9 Hz, 1H), 7.76 (dd, J=8.4, 0.6 Hz, 1H).

Workup

  1. extractionextracted with AcOEt
  2. customThe organic layer was separated
  3. washwashed with a saturated solution of NaCl
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customthe solvents evaporated in vacuo
  7. customThe crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 20/80)
  8. customThe desired fractions were collected
  9. customthe solvents evaporated in vacuo
  10. customthe residue triturated with DIPE

Sources & evidence

ORD record
ord-6cd5dbfb4a0146efbaa2baa223b8aa3d
Source dataset
uspto-grants-2014_12
Patent number
US08901125B2

Reaction notes

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