Acefylline → 2-(1,3-Dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-purin-7-yl)-n-[4-(1-hydroxy-1-methyl-ethyl)-phenyl]-acetamide

HRID 1942114Notes

Reaction equation

HRID 1942114 reaction equation
[N:1]1([C:12](=[O:13])[C:11]2[N:10]([CH2:14][C:15]([OH:17])=O)[CH:9]=[N:8][C:7]=2[N:5]([CH3:6])[C:3]1=[O:4])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:42][C:43]1[CH:48]=[CH:47][C:46]([C:49]([OH:52])([CH3:51])[CH3:50])=[CH:45][CH:44]=1>CN(C=O)C.CS(C)=O>[CH3:2][N:1]1[C:12](=[O:13])[C:11]2[N:10]([CH2:14][C:15]([NH:42][C:43]3[CH:44]=[CH:45][C:46]([C:49]([OH:52])([CH3:50])[CH3:51])=[CH:47][CH:48]=3)=[O:17])[CH:9]=[N:8][C:7]=2[N:5]([CH3:6])[C:3]1=[O:4]

Participants

5

Reactant 3

HCID 69550AcefyllineHCID 95432612-(4-Aminophenyl)propan-2-olHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 452544812-(1,3-Dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-purin-7-yl)-n-[4-(1-hydroxy-1-methyl-ethyl)-phenyl]-acetamide

Reagents, catalysts & solvents 1

HCID 3013483N,N-dimethylformamide; methylsulfinylmethaneSolvent

Procedure

To a 0° C. solution of acid 101 (0.32 g, 1.34 mmol) in DMF/DMSO (1:1, 20 mL) was added HATU (0.0.76 g, 2.01 mmol). The reaction was then stirred an additional 15 min at room temperature. The solution was cooled to 0° C. and amine 135 (0.30 g, 2.01 mmol) was added. The reaction was then stirred at rt overnight. The DMF was concentrated in vacuo and water was added to the reaction. The aqueous layer was extracted with EtOAc The ethyl acetate layer was then washed again with water and the organic layer was concentrated in vacuo. The product was purified by flash chromatography on silica gel eluting with EtOAc/hexanes and EtOAc/MeOH to yield 402 as a pure light brown semi solid (0.086 g, 17.5%). MS (APCI): m/z 372.2 [M−H]+ Anal. Calcd. For C18H21N5O4.0.35 EtOAc: C, 57.93; H, 5.96; N, 17.41; Found C, 58.36; H, 6.14; N, 16.96.

Workup

  1. temperatureThe solution was cooled to 0° C.
  2. stirringThe reaction was then stirred at rt overnight
  3. concentrationThe DMF was concentrated in vacuo and water
  4. additionwas added to the reaction
  5. extractionThe aqueous layer was extracted with EtOAc The ethyl acetate layer
  6. washwas then washed again with water
  7. concentrationthe organic layer was concentrated in vacuo
  8. customThe product was purified by flash chromatography on silica gel eluting with EtOAc/hexanes and EtOAc/MeOH

Sources & evidence

ORD record
ord-8e9b7bf858ae4e3795730fc6a490c8e4
Source dataset
uspto-grants-2013_03
Patent number
US08389529B2

Reaction notes

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