Methanol → HCID 59395726, compound

HRID 1097642Notes

Reaction equation

HRID 1097642 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])[N:7]([CH2:19][CH2:20][CH2:21][N:22]2[CH:26]=[N:25][C:24]([CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[N:23]2)[C:6]1=[O:34])[CH2:2][CH2:3][CH3:4].N1CCOCC1.CO>C1COCC1.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]([CH2:19][CH2:20][CH2:21][N:22]2[CH:26]=[N:25][C:24]([CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[N:23]2)[C:6]1=[O:34])[CH2:2][CH2:3][CH3:4]

Participants

6

Reactant 3

HCID 887MethanolHCID 8083MorpholineHCID 59395853HCID 59395853, compound

Product 1

HCID 59395726HCID 59395726, compoundYield 61.9%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 3-butyl-8-chloro-1-{3-[3-(phenylmethyl)-1H-1,2,4-triazol-1-yl]propyl}-7-(2-propen-1-yl)-3,7-dihydro-1H-purine-2,6-dione (669 mg, 1.39 mmol) in THF (7 ml) was degassed by applying a vacuum and then nitrogen was introduced. Pd(PPh3)4 (160 mg, 0.14 mmol) was added and the mixture degassed once more. Morpholine (1.2 ml, 13.9 mmol) was added and the mixture was stirred under nitrogen for 18 h, then partitioned between 2M HCl (aq) and EtOAc. The organic layer was separated and the aqueous layer extracted again with EtOAc. The combined extracts were washed with brine, dried (MgSO4) and concentrated, giving a yellow residue. MeOH was added and then passed down an aminopropyl SPE with the product eluting with 2-3% AcOH/MeOH. The product fractions were combined and concentrated giving a pale yellow solid (380 mg). Approximately a quarter of the material was purified by autoprep HPLC and rest was crystallised from MeOH:DMSO (1:1) giving the title compound as a white solid (125 mg, 31%).

Workup

  1. additionnitrogen was introduced
  2. customthe mixture degassed once more
  3. custompartitioned between 2M HCl (aq) and EtOAc
  4. customThe organic layer was separated
  5. extractionthe aqueous layer extracted again with EtOAc
  6. washThe combined extracts were washed with brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated
  9. customgiving a yellow residue
  10. washeluting with 2-3% AcOH/MeOH
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-ae91d3bf2c3142c7b69e9bd574583aa3
Source dataset
uspto-grants-2012_03
Patent number
US08143264B2

Reaction notes

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