Diisopropylethylamine → 8-(8-Oxa-bicyclo[3.2.1]oct-6-en-3-yl)-1,3-dipropyl-3,7-dihydro-purine-2,6-dione

HRID 395889Notes

Reaction equation

HRID 395889 reaction equation
[CH:1]12[O:8][CH:5]([CH:6]=[CH:7]1)[CH2:4][CH:3]([C:9](O)=O)[CH2:2]2.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[NH2:37][C:38]1[C:39](=[O:52])[N:40]([CH2:49][CH2:50][CH3:51])[C:41](=[O:48])[N:42]([CH2:45][CH2:46][CH3:47])[C:43]=1[NH2:44].CCN(C(C)C)C(C)C>CN(C=O)C>[CH:5]12[O:8][CH:1]([CH:7]=[CH:6]1)[CH2:2][CH:3]([C:9]1[NH:37][C:38]3[C:39](=[O:52])[N:40]([CH2:49][CH2:50][CH3:51])[C:41](=[O:48])[N:42]([CH2:45][CH2:46][CH3:47])[C:43]=3[N:44]=1)[CH2:4]2

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 181730508-Oxabicyclo[3.2.1]oct-6-ene-3-carboxylic acidHCID 187676182,4(1H,3H)-Pyrimidinedione, 5,6-diamino-1,3-dipropyl-, hydrochloride (1:1)

Product 1

HCID 102911968-(8-Oxa-bicyclo[3.2.1]oct-6-en-3-yl)-1,3-dipropyl-3,7-dihydro-purine-2,6-dioneYield 77.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 8-oxa-bicyclo[3.2.1]oct-6-ene-3-carboxylic acid (0.25 mmol, 0.0386 g), HATU (0.25 mmol, 0.0952 g), and 5,6-diamino-1,3-dipropyl-1H-pyrimidine-2,4-dione hydrochloride (Daly, J. W. et al., J. Med. Chem., 1985, 28 (4), 487) (0.25 mmol, 0.0658 g) in DMF (2.5 ml) was added iPr2NEt (0.75 mmol, 0.13 ml). The reaction was stirred overnight at room temperature. It was concentrated at the pump to remove DMF. The residue was dissolved in EtOAc and washed with 1N HCl, 5% NaHCO3, and brine and dried (MgSO4). Filtration and evaporation followed by flash column chromatography, eluting with a THF/CH2Cl2 gradient provided the desired product (0.067 g, 74%) as an oil that solidified on standing. 1H NMR (300 MHz, CDCl3): 0.90 (t, 3H, J=7.4 Hz), 0.97 (t, 3H, J=7.3 Hz), 1.53-1.72 (m, 6H), 1.95-2.03 (m, 2H), 3.0 (br m, 1H), 3.82-3.91 (m, 4H), 4.79 (br s, 2H), 6.18 (s, 2H).

Workup

  1. concentrationIt was concentrated at the pump
  2. customto remove DMF
  3. dissolutionThe residue was dissolved in EtOAc
  4. washwashed with 1N HCl, 5% NaHCO3, and brine
  5. dry with materialdried (MgSO4)
  6. filtrationFiltration and evaporation
  7. washeluting with a THF/CH2Cl2 gradient

Sources & evidence

ORD record
ord-0f747ec8738b470ca2c5c395c090b9a9
Source dataset
uspto-grants-2003_08
Patent number
US06605600B1

Reaction notes

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