Hydrochloric Acid → HCID 59299574, compound

HRID 1943828Notes

Reaction equation

HRID 1943828 reaction equation
[Cl:1][C:2]1[N:10](CC=C)[C:9]2[C:8](=[O:14])[N:7]([CH3:15])[C:6](=[O:16])[NH:5][C:4]=2[N:3]=1.C([O-])([O-])=O.[Na+].[Na+].Br[CH2:24][CH2:25][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.O.C(OCC)(=O)C>[Cl:1][C:2]1[NH:10][C:9]2[C:8](=[O:14])[N:7]([CH3:15])[C:6](=[O:16])[N:5]([CH2:24][CH2:25][CH2:26][C:27]#[N:28])[C:4]=2[N:3]=1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 8083MorpholineHCID 10340Sodium CarbonateHCID 214124-BromobutyronitrileHCID 59299531HCID 59299531, compound

Product 1

HCID 59299574HCID 59299574, compoundYield 51%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 8-chloro-1-methyl-7-(2-propen-1-yl)-3,7-dihydro-1H-purine-2,6-dione (70 mg, 0.292 mmol) and Na2CO3 (37 mg, 0.35 mmol) in DMF (3 ml) was added 4-bromobutyronitrile (0.035 ml, 0.35 mmol). The mixture was stirred at room temperature overnight, before degassing under a gentle vacuum and introducing nitrogen. Pd(PPh3)4 (50 mg, 0.044 mmol) and morpholine (0.254 ml, 2.92 mmol) was then added sequentially. After two hours stirring at room temperature further fresh Pd(PPh3)4 (50 mg, 0.044 mmol) was added and stirring continued overnight. The reaction mixture was partioned between ethyl acetate (20 ml) and water (20 ml) adding a small amount of 2M HCl to aid separation. 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 3-5% AcOH/MeOH. The product fraction was concentrated to afford the title compound 39.7 mg (51%); NMR; δH (400 MHz, d6-DMSO) 1.91-2.00 (m, 2H), 2.55 (t, 2H, J=7 Hz), 3.22 (s, 3H), 4.03 (t, 2H, J=7 Hz), 14.49 (br.s, 1H); m/z 268.1 [MH+].

Workup

  1. custombefore degassing under a gentle vacuum
  2. additionintroducing nitrogen
  3. additionwas added
  4. stirringstirring continued overnight
  5. customseparation
  6. customThe organic layer was separated
  7. washwashed with brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated
  10. washeluting with MeOH
  11. concentrationThe product fraction was concentrated

Sources & evidence

ORD record
ord-2290dae5a676460699f5f5f42c00a43d
Source dataset
uspto-grants-2013_03
Patent number
US08394808B2

Reaction notes

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