Hydrochloric Acid → (8-chloro-2,6-dioxo-3-propyl-2,3,6,7-tetrahydro-1H-purin-1-yl)acetonitrile

HRID 2386638

Reaction equation

HRID 2386638 reaction equation
[Cl:1][C:2]1[N:10](CC=C)[C:9]2[C:8](=[O:14])[NH:7][C:6](=[O:15])[N:5]([CH2:16][CH2:17][CH3:18])[C:4]=2[N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:26][C:27]#[N:28].N1CCOCC1.Cl>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>[Cl:1][C:2]1[NH:10][C:9]2[C:8](=[O:14])[N:7]([CH2:26][C:27]#[N:28])[C:6](=[O:15])[N:5]([CH2:16][CH2:17][CH3:18])[C:4]=2[N:3]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8083MorpholineHCID 10796Cesium carbonateHCID 11534BromoacetonitrileHCID 592995678-chloro-7-(2-propen-1-yl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione

Product 1

HCID 59299547(8-chloro-2,6-dioxo-3-propyl-2,3,6,7-tetrahydro-1H-purin-1-yl)acetonitrileYield 33%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 8-chloro-7-(2-propen-1-yl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione (0.067 g, 0.25 mmol) in DMF (2 ml) was treated with caesium carbonate (0.082 g, 0.25 mmol) and bromoacetonitrile (0.044 g, 0.37 mmol). The mixture was heated at 80° C. for 4 hours then cooled to ambient temperature. The DMF was removed in vacuo and the residue treated with THF (2 ml). The solvent was degassed by the successive application of vacuum and nitrogen pressure to the reaction mixture. The mixture was then treated with morpholine (0.035 ml, 0.4 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.03 g, 0.026 mmol). After 2 hours the mixture was treated with 2M aqueous hydrochloric acid (2 ml) and the product extracted with chloroform (3×5 ml). The organic fractions were combined and evaporated. The residue was subjected to purification by mass-directed HPLC to afford the title compound as a white solid (0.022 g, 33%). NMR; δH (400 MHz, d6-DMSO), 0.88 (t, 3H, J=7.5 Hz), 1.63-1.74 (m, 2H), 3.91 (t, 2H, J=7.5 Hz), 4.87 (s, 2H), NH not observed to δH 14; m/z 268 [MH+].

Workup

  1. temperaturethen cooled to ambient temperature
  2. customThe DMF was removed in vacuo
  3. additionthe residue treated with THF (2 ml)
  4. customThe solvent was degassed by the successive application of vacuum and nitrogen pressure to the reaction mixture
  5. extractionthe product extracted with chloroform (3×5 ml)
  6. customevaporated
  7. customThe residue was subjected to purification by mass-directed HPLC

Sources & evidence

ORD record
ord-0b346510caca4033910ae1ac01478cd6
Source dataset
uspto-grants-2012_09
Patent number
US08268839B2

Linked notes

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