4-(4'-Chloro-2'-(methylthio)-4,5'-bipyrimidin-2-ylamino)benzonitrile → 4-(4'-Isopropyl-2'-(methylthio)-4,5'-bipyrimidin-2-ylamino)benzonitrile

HRID 2359776Notes

Reaction equation

HRID 2359776 reaction equation
Cl[C:2]1[C:7]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]([NH:14][C:15]3[CH:22]=[CH:21][C:18]([C:19]#[N:20])=[CH:17][CH:16]=3)[N:9]=2)=[CH:6][N:5]=[C:4]([S:23][CH3:24])[N:3]=1.[CH:25]([Mg]Br)([CH3:27])[CH3:26]>C1COCC1.CN1C(=O)CCC1>[CH:25]([C:2]1[C:7]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]([NH:14][C:15]3[CH:22]=[CH:21][C:18]([C:19]#[N:20])=[CH:17][CH:16]=3)[N:9]=2)=[CH:6][N:5]=[C:4]([S:23][CH3:24])[N:3]=1)([CH3:27])[CH3:26]

Participants

5

Reactant 2

HCID 867055934-(4'-Chloro-2'-(methylthio)-4,5'-bipyrimidin-2-ylamino)benzonitrileHCID 178418365HCID 178418365, compound2×

Product 1

HCID 679837074-(4'-Isopropyl-2'-(methylthio)-4,5'-bipyrimidin-2-ylamino)benzonitrileYield 40.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

4-(4′-Chloro-2′-(methylthio)-4,5′-bipyrimidin-2-ylamino)benzonitrile (35) (125 mg, 0.352 mmol) and ferric acetylacetonate (12.44 mg, 0.035 mmol) were dissolved in THF (1791 μl) and NMP (134 μl), then isopropylmagnesium bromide (528 μl, 0.528 mmol) was added dropwise. According to LC/MS, approximately 40% conversion was observed. Additional isopropylmagnesium bromide (528 μl, 0.528 mmol) was added, and the reaction was stirred at rt for an additional 1 hour. The reaction was quenched with 1N HCl, then was extract with EtOAc. The organic extracts were combined, washed with brine, dried over sodium sulfate, then concentrated in vacuo. The crude product was dry-loaded onto silica gel, then was purified by Biotage™ silica gel chromatgraphy [25 g SNAP column, 30% EtOAc/heptane to 100% EtOAc] to obtain the desired product (51.1 mg, 40%). MS (ES+): m/z=363.3 [M+1] (100). HPLC: tR=1.70 minutes over 3 minutes.

Workup

  1. customThe reaction was quenched with 1N HCl
  2. extractionwas extract with EtOAc
  3. washwashed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customwas purified by Biotage™ silica gel chromatgraphy [25 g SNAP column, 30% EtOAc/heptane to 100% EtOAc]

Sources & evidence

ORD record
ord-8aeb04bc050444a48bc2ed92fbeb102f
Source dataset
uspto-grants-2014_04
Patent number
US08685993B2

Reaction notes

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