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

HRID 2359775Notes

Reaction equation

HRID 2359775 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.[CH2:25]([Mg]Br)[CH3:26]>C1COCC1.CN1C(=O)CCC1>[CH2:25]([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)[CH3:26]

Participants

5

Reactant 2

HCID 867055934-(4'-Chloro-2'-(methylthio)-4,5'-bipyrimidin-2-ylamino)benzonitrileHCID 178418443HCID 178418443, compound

Product 1

HCID 679838474-(4'-Ethyl-2'-(methylthio)-4,5'-bipyrimidin-2-ylamino)benzonitrileYield 26.7%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

4-(4′-Chloro-2′-(methylthio)-4,5′-bipyrimidin-2-ylamino)benzonitrile (35) (205 mg, 0.526 mmol) and ferric acetylacetonate (18.57 mg, 0.053 mmol) were dissolved in THF (3305 μl) and NMP (248 μl), then ethylmagnesium bromide (789 μl, 0.789 mmol) was added dropwise under nitrogen. 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 and purified by Biotage™ silica gel chromatography [25 g SNAP column, 30% EtOAc/heptane to 100% EtOAc] to obtain 49 mg of the desired product (21%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.19 (t, J=7.58 Hz, 3H) 2.59 (s, 3H) 2.95 (q, J=7.58 Hz, 2H) 7.25 (d, J=5.05 Hz, 1H) 7.68-7.78 (m, 2H) 7.95-8.03 (m, 2H) 8.67-8.75 (m, 2H) 10.33 (s, 1H). MS (ES+): m/z=349.5 [M+1] (100). HPLC: tR=1.57 minutes over 3 minutes. Purity: 93% [HPLC (LC/MS) at 220 nm].

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. custompurified by Biotage™ silica gel chromatography [25 g SNAP column, 30% EtOAc/heptane to 100% EtOAc]

Sources & evidence

ORD record
ord-1af525d078a548368cbef43b381f2c45
Source dataset
uspto-grants-2014_04
Patent number
US08685993B2

Reaction notes

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