1,2-Dimethoxyethane → HCID 178434538, compound

HRID 1853032Notes

Reaction equation

HRID 1853032 reaction equation
Cl[C:2]1[N:7]2[CH:8]=[CH:9][N:10]=[C:6]2[CH:5]=[C:4]([C:11]2[CH:12]=[N:13][N:14]([CH3:16])[CH:15]=2)[N:3]=1.[CH3:17][C:18]1[C:22](B2OC(C)(C)C(C)(C)O2)=[CH:21][NH:20][N:19]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].COCCOC>CCOC(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.CO>[CH3:16][N:14]1[CH:15]=[C:11]([C:4]2[N:3]=[C:2]([C:22]3[C:18]([CH3:17])=[N:19][NH:20][CH:21]=3)[N:7]3[CH:8]=[CH:9][N:10]=[C:6]3[CH:5]=2)[CH:12]=[N:13]1

Participants

8

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 62657Potassium Phosphate, TribasicHCID 86685297HCID 86685297, compoundHCID 178434487HCID 178434487, compound

Product 1

HCID 178434538HCID 178434538, compoundYield 27.7%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a flask charged with 5-chloro-7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine (Preparation J; 0.650 g, 2.78 mmol), 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.868 g, 4.17 mmol), and 2 M K3PO4 (4.17 mL, 8.35 mmol) was added 20 mL of DME and argon was bubbled through for 15 minutes before tetrakis(triphenylphosphine)palladium (0) (0.321 g, 0.278 mmol) was added. The flask was sealed and the reaction was heated to 100° C. for 4 hours, then allowed to cool to ambient temperature and stirred overnight. The reaction mixture was diluted with EtOAc (300 mL) and washed with aqueous saturated sodium bicarbonate (50 mL). The organic layer was washed with brine (50 mL), dried over MgSO4, filtered, and concentrated under reduced pressure. The crude material was taken up in DCM in preparation for chromatography when a precipitate began to form and continued to thicken over time. The addition of minimal MeOH (0.5 mL) did not dissolve the precipitate. The solid was collected by vacuum filtration and retained. The rinse was purified by means of silica gel chromatography eluting with a gradient of 5-10% MeOH in EtOAc containing 1% NH4OH. This was successful at generating material that was combined with the solid above to afford 7-(1-methyl-1H-pyrazol-4-yl)-5-(3-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine (0.215 g, 0.770 mmol, 27.7% yield). MS (apci) m/z=280.1 (M+H).

Workup

  1. additionwas added
  2. customThe flask was sealed
  3. temperatureto cool to ambient temperature
  4. washwashed with aqueous saturated sodium bicarbonate (50 mL)
  5. washThe organic layer was washed with brine (50 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude material was taken up in DCM in preparation for chromatography when a precipitate
  10. customto form
  11. dissolutiondid not dissolve the precipitate
  12. filtrationThe solid was collected by vacuum filtration
  13. customThe rinse was purified by means of silica gel chromatography
  14. washeluting with a gradient of 5-10% MeOH in EtOAc containing 1% NH4OH

Sources & evidence

ORD record
ord-4bd699350cac4bb0bd347f9519695102
Source dataset
uspto-grants-2015_02
Patent number
US08962596B2

Reaction notes

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