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

HRID 751300Notes

Reaction equation

HRID 751300 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]2[N:6]([N:8]=[CH:9][CH:10]=2)[CH:7]=1.[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.C(=O)([O-])[O-].[K+].[K+].CS(C)=O>C(OCC)C.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>[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][C:5]3[N:6]([N:8]=[CH:9][CH:10]=3)[CH:7]=2)=[C:19]2[CH2:24][CH2:23][CH2:22][N:20]2[N:21]=1

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 11430Potassium CarbonateHCID 222367016-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 117796786-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-pyrazolo[1,5-a]pyrimidineYield 26.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 3283Diethyl EtherSolvent

Procedure

To a microwave tube, add 6-bromo-pyrazolo[1,5-a]pyrimidine (0.175 g, 0.884 mmol), 2-(pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-3-boronic acid (0.25 g, 1.09 mmol), tetrakis(triphenylphosphine)palladium(0) (31 mg, 0.027 mmol), 2M aqueous potassium carbonate (0.5 mL, 1.0 mmol) and dimethylsulfoxide (1.5 mL). Irradiate the reaction in a microwave reactor set at 110° C., 50 Watts, 10 min with external cooling. Dilute the reaction mixture with diethyl ether (250 mL) and extract the product into 0.1M aqueous hydrochloric acid (450 mL). Make the aqueous solution basic by adding 5M aqueous sodium hydroxide (25 mL) and extract with dichloromethane (300 mL). Filter the organic layer and concentrate under reduced pressure. Recrystallize the resulting solid from ethyl acetate, filter, rinse with ethyl acetate, and dry at 100° C. under vacuum to obtain 70 mg (26%) of the title compound as a tan solid. MS (electrospray, m/z) 302.9 (M+1).

Workup

  1. customIrradiate
  2. customthe reaction in a microwave reactor
  3. customset at 110° C.
  4. custom50 Watts, 10 min
  5. extractionextract the product into 0.1M aqueous hydrochloric acid (450 mL)
  6. additionby adding 5M aqueous sodium hydroxide (25 mL)
  7. extractionextract with dichloromethane (300 mL)
  8. filtrationFilter the organic layer
  9. concentrationconcentrate under reduced pressure
  10. customRecrystallize the resulting solid from ethyl acetate
  11. filtrationfilter
  12. washrinse with ethyl acetate
  13. customdry at 100° C. under vacuum

Sources & evidence

ORD record
ord-caf5fc248e714518a0f5bec0c9faeb8d
Source dataset
uspto-grants-2008_07
Patent number
US07405299B2

Reaction notes

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