Lawesson's reagent → HCID 68157800, compound

HRID 243393Notes

Reaction equation

HRID 243393 reaction equation
COC1C=CC(P2(=S)SP(C3C=CC(OC)=CC=3)(=S)S2)=CC=1.[F:23][C:24]1[CH:29]=[CH:28][C:27]([NH:30][C:31](=O)[C@@H:32]([NH:34][C:35]2[N:43]=[CH:42][N:41]=[C:40]3[C:36]=2[N:37]=[CH:38][N:39]3C2CCCCO2)[CH3:33])=[C:26]([NH:51][C:52]2[N:57]=[CH:56][CH:55]=[CH:54][N:53]=2)[CH:25]=1>O1CCCC1>[F:23][C:24]1[CH:29]=[CH:28][C:27]2[N:30]=[C:31]([C@@H:32]([NH:34][C:35]3[N:43]=[CH:42][N:41]=[C:40]4[C:36]=3[NH:37][CH:38]=[N:39]4)[CH3:33])[N:51]([C:52]3[N:57]=[CH:56][CH:55]=[CH:54][N:53]=3)[C:26]=2[CH:25]=1

Participants

4

Reactant 2

HCID 87949Lawesson's reagentHCID 68157785HCID 68157785, compound

Product 1

HCID 68157800HCID 68157800, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

2,4-Bis(4-methoxyphenyl)-2,4-dithioxo-1,3,2,4-dithiadiphosphetane (369 mg, 0.91 mmol) was added to (S)—N-[4-fluoro-2-(pyrimidin-2-ylamino)phenyl]-2-[9-(tetrahydropyran-2-yl)-9H-purin-6-ylamino]propionamide (109 mg, 0.23 mmol) in tetrahydrofuran (5.0 ml) and heated to 80° C. overnight. The reaction mixture was cooled and concentrated in vacuo. The residue was taken up in EtOAc/1M hydrochloric acid (aqueous), and the aqueous layer extracted with EtOAc three times. The aqueous layer was neutralised with sodium hydroxide (1M aqueous) and extracted with EtOAc (×3). The neutral organic fractions were washed with brine, dried (Na2SO4) and concentrated in vacuo. The product was purified by chromatography (SiO2, 0-20% methanol in DCM) to yield 261 (35 mg, 41%). LCMS: RT 3.08 min [M+H]+ 376.0. 1H NMR (CDCl3, 400 MHz): δ 8.90 (2H, d, J=4.9 Hz), 8.02 (2H, s), 7.97 (1H, dd, J=9.8, 2.7 Hz), 7.60 (1H, dd, J=8.7, 5.0 Hz), 7.42 (1H, t, J=4.8 Hz), 7.08 (1H, td, J 9.0, 2.6 Hz), 6.52 (1H, br s), 1.83 (3H, d, J=6.8 Hz)

Workup

  1. temperatureThe reaction mixture was cooled
  2. concentrationconcentrated in vacuo
  3. extractionthe aqueous layer extracted with EtOAc three times
  4. extractionextracted with EtOAc (×3)
  5. washThe neutral organic fractions were washed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customThe product was purified by chromatography (SiO2, 0-20% methanol in DCM)

Sources & evidence

ORD record
ord-25512335058241f581a31a495559c7e6
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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