Cesium fluoride → HCID 68865418, compound

HRID 494149Notes

Reaction equation

HRID 494149 reaction equation
[CH2:1]([O:8][C:9]1[C:17]2[C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)[N:14]=[C:13](Br)[C:12]=2[N:11]2[CH2:28][CH2:29][N:30]([CH3:33])[C:31](=[O:32])[C:10]=12)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N:34]1[CH:39]=[C:38](B(O)O)[CH:37]=[N:36][CH:35]=1.[F-].[Cs+]>O1CCOCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)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]>[CH2:1]([O:8][C:9]1[C:17]2[C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)[N:14]=[C:13]([C:38]3[CH:39]=[N:34][CH:35]=[N:36][CH:37]=3)[C:12]=2[N:11]2[CH2:28][CH2:29][N:30]([CH3:33])[C:31](=[O:32])[C:10]=12)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 25953Cesium fluorideHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 68866000HCID 68866000, compound

Product 1

HCID 68865418HCID 68865418, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 178418851HCID 178418851, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 10-(benzyloxy)-4-bromo-2-(4-fluorobenzyl)-8-methyl-7,8-dihydropyrazino[1′,2′:1,5]pyrrolo[2,3-d]pyridazine-1,9(2H,6H)-dione (0.10 g, 0.19 mmol; Example 160, step 1), pyrimidine-5-boronic acid (73 mg, 0.59 mmol), cesium fluoride (0.12 g, 0.78 mmol), bis(tri-t-butylphosphine)palladium(0) (10 mg, 0.02 mmol), and tris(dibenzylideneacetone)dipalladium (18 mg, 0.02 mmol) in dioxane (3 mL) was purged with nitrogen for 2 minutes and heated in a sealed tube at 80° C. overnight. The reaction mixture was filtered through a pad of Celite, and the filtrate was concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with 0 to 20% methanol in chloroform gradient. Collection and concentration of appropriate fractions afforded the title material.

Workup

  1. customwas purged with nitrogen for 2 minutes
  2. filtrationThe reaction mixture was filtered through a pad of Celite
  3. concentrationthe filtrate was concentrated under vacuum
  4. customCollection and concentration of appropriate fractions

Sources & evidence

ORD record
ord-5e9bc5f02a8945fc9240b156f7029b7c
Source dataset
uspto-grants-2009_05
Patent number
US07538112B2

Reaction notes

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