Bromide ion → Omipalisib

HRID 472091Notes

Reaction equation

HRID 472091 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][CH:6]=[C:5]2[C:12]1[CH:17]=[CH:16][N:15]=[N:14][CH:13]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].[Br-].Br[C:43]1[CH:44]=[C:45]([NH:51][S:52]([C:55]2[CH:60]=[CH:59][C:58]([F:61])=[CH:57][C:56]=2[F:62])(=[O:54])=[O:53])[C:46]([O:49][CH3:50])=[N:47][CH:48]=1>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[F:62][C:56]1[CH:57]=[C:58]([F:61])[CH:59]=[CH:60][C:55]=1[S:52]([NH:51][C:45]1[C:46]([O:49][CH3:50])=[N:47][CH:48]=[C:43]([C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[N:8]=[CH:7][CH:6]=[C:5]3[C:12]2[CH:17]=[CH:16][N:15]=[N:14][CH:13]=2)[CH:44]=1)(=[O:54])=[O:53]

Participants

8

Reactant 5

HCID 259Bromide ionHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 59859951N-(5-bromo-2-methoxypyridin-3-yl)-2,4-difluorobenzenesulfonamideHCID 667823086-Bromo-4-(pyridazin-4-yl)quinoline

Product 1

HCID 25167777OmipalisibYield 76.6%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalyst2×HCID 312751,4-DioxaneSolvent

Procedure

A slurry of 6-bromo-4-(4-pyridazinyl)quinoline (4.8 g, 16.78 mmol), bis(pinacolato)diboron (4.69 g, 18.45 mmol), PdCl2(dppf)-CH2Cl2 (530 mg, 0.649 mmol) and potassium acetate (3.29 g, 33.6 mmol) in anhydrous 1,4-dioxane (120 ml) was heated at 100° C. for 3 h. The complete disappearance of the starting bromide was observed by LCMS. The reaction was then treated with N-[5-bromo-2-(methyloxy)-3-pyridinyl]-2,4-difluorobenzenesulfonamide (6.68 g, 17.61 mmol) and another portion of PdCl2(dppf)-CH2Cl2 (550 mg, 0.673 mmol), then heated at 110° C. for 16 h. The reaction was allowed to cool to room temperature, filtered, and concentrated. Purification of the residue by chromatography (Analogix; 5% MeOH/5% CH2Cl2/90% EtOAC) gave 6.5 g (76%) desired product. MS (ES)+ m/e 505.9 [M+H]+.

Workup

  1. filtrationfiltered
  2. concentrationconcentrated
  3. customPurification of the residue by chromatography (Analogix; 5% MeOH/5% CH2Cl2/90% EtOAC)

Sources & evidence

ORD record
ord-c2e43ffae58c4b42920c7a1bf53cd842
Source dataset
uspto-grants-2014_01
Patent number
US08633187B2

Reaction notes

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