4-Bromopyridinium chloride → HCID 71611179, compound

HRID 1484689Notes

Reaction equation

HRID 1484689 reaction equation
[CH2:1]([O:3][C:4]1[CH:27]=[C:26]([F:28])[C:7]([CH2:8][N:9]2[C:13]([O:14][CH3:15])=[C:12]([CH3:16])[C:11]([C:17]3[N:22]=[C:21]([NH2:23])[C:20]([O:24][CH3:25])=[CH:19][N:18]=3)=[N:10]2)=[C:6]([F:29])[CH:5]=1)[CH3:2].Cl.Br[C:32]1[CH:37]=[CH:36][N:35]=[CH:34][CH:33]=1.C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>CN(C=O)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:3][C:4]1[CH:5]=[C:6]([F:29])[C:7]([CH2:8][N:9]2[C:13]([O:14][CH3:15])=[C:12]([CH3:16])[C:11]([C:17]3[N:22]=[C:21]([NH:23][C:32]4[CH:37]=[CH:36][N:35]=[CH:34][CH:33]=4)[C:20]([O:24][CH3:25])=[CH:19][N:18]=3)=[N:10]2)=[C:26]([F:28])[CH:27]=1)[CH3:2]

Participants

6

Reactant 3

HCID 881004-Bromopyridinium chlorideHCID 634876Binap, (A+-)-HCID 89648403HCID 89648403, compound

Product 1

HCID 71611179HCID 71611179, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

619 mg of 2-[1-(4-ethoxy-2,6-difluorobenzyl)-5-methoxy-4-methyl-1H-pyrazol-3-yl]-5-methoxypyrimidin-4-amine 1-5-1 (1.53 mmol, 1.0 eq.), 445-38 mg of 4-bromopyridine hydrochloride (1:1) (2.29 mmol, 1.5 eq.), 190.15 mg of (R)-(+)-2,2′-bis(diphenylphosphino)-1,1′-binaphtyl (305 mmol, 0.2 eq.), 587 mg of sodium-tert-buylat (6.12 mmol, 4.0 eq.) and 419 mg of tris-(dibenzylideneacetone)dipalladium(0) (0.458 mmol, 0.3 eq.) were suspended in 10 mL of dry DMF and stirred under nitrogen atmosphere at 110° C. bath temperature for 24 hours. The reaction mixture was partitioned between half saturated aqueous ammonium chloride solution and DCM. The separated aqueous layer was extracted twice with DCM. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography (hexane (0-100%)/ethyl acetate). The column was washed with methanol to receive a 50% pure target compound. This was stirred with acetone and the suspension was filtered off.

Workup

  1. customThe reaction mixture was partitioned between half saturated aqueous ammonium chloride solution and DCM
  2. extractionThe separated aqueous layer was extracted twice with DCM
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography (hexane (0-100%)/ethyl acetate)
  7. washThe column was washed with methanol
  8. stirringThis was stirred with acetone
  9. filtrationthe suspension was filtered off

Sources & evidence

ORD record
ord-cd415296a6624fe3bee669bf8efef5f5
Source dataset
uspto-grants-2016_08
Patent number
US09422268B2

Reaction notes

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