Chloroacetonitrile → HCID 59299563, compound

HRID 2386636Notes

Reaction equation

HRID 2386636 reaction equation
[CH2:1]([N:5]1[C:13]2[N:12]=[C:11]([Cl:14])[N:10](CC=C)[C:9]=2[C:8](=[O:18])[NH:7][C:6]1=[O:19])[CH2:2][CH2:3][CH3:4].C([O-])([O-])=O.[Cs+].[Cs+].Cl[CH2:27][C:28]#[N:29].N1CCOCC1>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([N:5]1[C:13]2[N:12]=[C:11]([Cl:14])[NH:10][C:9]=2[C:8](=[O:18])[N:7]([CH2:27][C:28]#[N:29])[C:6]1=[O:19])[CH2:2][CH2:3][CH3:4]

Participants

7

Reactant 4

HCID 7856ChloroacetonitrileHCID 8083MorpholineHCID 10796Cesium carbonateHCID 592995823-butyl-8-chloro-7-(2-propen-1-yl)-3,7-dihydro-1H-purine-2,6-dione

Product 1

HCID 59299563HCID 59299563, compoundYield 26.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a mixture of 3-butyl-8-chloro-7-(2-propen-1-yl)-3,7-dihydro-1H-purine-2,6-dione (200 mg, 0.707 mmol) and Cs2CO3 (254 mg, 0.778 mmol) in anhydrous DMF (5 ml) was added chloroacetonitrile (0.054 ml, 0.85 mmol). The mixture was heated at 50° C. for 18 hours then allowed to cool to rt and degassed under a gentle vacuum then nitrogen introduced. This was repeated twice. Pd(PPh3)4 (82 mg, 0.071 mmol) was added and the mixture degassed once more, before morpholine (0.617 ml, 7.07 mmol) was added and the mixture left to stir for 3 hours at rt. The mixture was partitioned between 2M HCl(aq) and EtOAc. The organic layer was separated, washed with brine, dried (MgSO4) and concentrated. The residue was taken up in MeOH and passed down an amino-propyl SPE (5 g), eluting with MeOH followed by 5-10% AcOH/MeOH. The product fraction was concentrated giving the title compound 52 mg (26%); NMR; δH (400 MHz, d6-DMSO) 0.90 (t, 3H, J=7.5 Hz), 1.26-1.37 (m, 2H), 1.60-1.69 (m, 2H), 3.94 (t, 2H, J=7.5 Hz), 4.87 (s, 2H), 14.72 (br s, 1H); m/z 299.2 [MNH4+].

Workup

  1. temperatureto cool to rt
  2. customdegassed under a gentle vacuum
  3. additionnitrogen introduced
  4. additionwas added
  5. waitthe mixture left
  6. customThe mixture was partitioned between 2M HCl(aq) and EtOAc
  7. customThe organic layer was separated
  8. washwashed with brine
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated
  11. washeluting with MeOH
  12. concentrationThe product fraction was concentrated

Sources & evidence

ORD record
ord-a36f95b6ac9143a984bddc69d5585dff
Source dataset
uspto-grants-2012_09
Patent number
US08268839B2

Reaction notes

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