Water → HCID 67457604, compound

HRID 1852967Notes

Reaction equation

HRID 1852967 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12](Cl)[N:11]3[CH:15]=[CH:16][N:17]=[C:10]3[CH:9]=2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].CC1(C)C(C)(C)OB([C:32]2[CH:33]=[N:34][N:35]([CH2:37][O:38][CH2:39][CH2:40][Si:41]([CH3:44])([CH3:43])[CH3:42])[CH:36]=2)O1.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>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]([C:32]3[CH:33]=[N:34][N:35]([CH2:37][O:38][CH2:39][CH2:40][Si:41]([CH3:44])([CH3:43])[CH3:42])[CH:36]=3)[N:11]3[CH:15]=[CH:16][N:17]=[C:10]3[CH:9]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 574776664-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole2×HCID 86685301HCID 86685301, compound

Product 1

HCID 67457604HCID 67457604, compoundYield 39.8%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
70 °C

Procedure

To a flask charged with 7-(4-bromophenyl)-5-chloroimidazo[1,2-c]pyrimidine (2.68 g, 8.685 mmol), potassium carbonate (3.601 g, 26.06 mmol), and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole (Preparation E; 6.628 g, 17.37 mmol) were combined in a glass bomb and the vessel was evacuated and backfilled with argon. To the reaction was added 100 mL of DME and then water (1.252 mL, 69.48 mmol) and argon was bubbled through the reaction for 20 minutes before tetrakis(triphenylphosphine)palladium (0) (1.004 g, 0.8685 mmol) was added in one portion. The reaction was fitted with a septum and argon was bubbled through for 10 minutes before the reaction was sealed and heated to 70° C. for 4 hours 4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole (Preparation E; 3.3 g, 8.6 mmol) was added. Argon was bubbled through for 10 minutes before the reaction was sealed and heated to 70° C. for 3 hours. The reaction was diluted with 10% methanol in DCM (300 mL), dried with MgSO4, filtered, and then concentration under reduced pressure. The resultant crude was purified by silica gel chromatography eluting with a gradient of 30-75% ethyl acetate in hexanes to afford the title compound (1.625 g, 3.454 mmol, 39.77% yield). MS (apci) m/z=470.1 (M+H).

Workup

  1. customthe vessel was evacuated
  2. additionTo the reaction was added 100 mL of DME
  3. additionwas added in one portion
  4. customThe reaction was fitted with a septum and argon
  5. customwas bubbled through for 10 minutes before the reaction
  6. customwas sealed
  7. additionwas added
  8. customArgon was bubbled through for 10 minutes before the reaction
  9. customwas sealed
  10. additionThe reaction was diluted with 10% methanol in DCM (300 mL)
  11. dry with materialdried with MgSO4
  12. filtrationfiltered
  13. concentrationconcentration under reduced pressure
  14. customThe resultant crude was purified by silica gel chromatography
  15. washeluting with a gradient of 30-75% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-4683d45614b64dd7bf5b80b58d0ed816
Source dataset
uspto-grants-2015_02
Patent number
US08962596B2

Reaction notes

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