3-Cyclobutene-1,2-dione, 3,4-dimethoxy- → HCID 86647567, compound

HRID 2382490Notes

Reaction equation

HRID 2382490 reaction equation
FC(F)(F)C(O)=O.[CH2:8]([NH:10][C:11]([C@@H:13]1[C@@H:17]([OH:18])[C@@H:16]([OH:19])[C@H:15]([N:20]2[CH:28]=[N:27][C:26]3[C:21]2=[N:22][C:23]([N:44]2[CH2:48][CH2:47][C@@H:46]([NH2:49])[CH2:45]2)=[N:24][C:25]=3[NH:29][CH2:30][CH:31]([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[O:14]1)=[O:12])[CH3:9].[CH3:50][O:51][C:52]1[C:53](=O)[C:54](=[O:58])[C:55]=1[O:56]C>CCO.CN(C1C=CN=CC=1)C>[CH2:8]([NH:10][C:11]([C@@H:13]1[C@@H:17]([OH:18])[C@@H:16]([OH:19])[C@H:15]([N:20]2[CH:28]=[N:27][C:26]3[C:21]2=[N:22][C:23]([N:44]2[CH2:48][CH2:47][C@@H:46]([NH:49][C:53]4[C:54](=[O:58])[C:55](=[O:56])[C:52]=4[O:51][CH3:50])[CH2:45]2)=[N:24][C:25]=3[NH:29][CH2:30][CH:31]([C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[O:14]1)=[O:12])[CH3:9]

Participants

5

Reactant 2

HCID 1232273-Cyclobutene-1,2-dione, 3,4-dimethoxy-HCID 66630764HCID 66630764, compound2×

Product 1

HCID 86647567HCID 86647567, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 702EthanolSolvent

Procedure

A mixture comprising (2S,3S,4R,5R)-5-[2-((R)-3-Amino-pyrrolidin-1-yl)-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-3,4-dihydroxy-tetrahydro-furan-2-carboxylic acid ethylamide trifluoroacetate (Intermediate E) and 3,4-dimethoxy-3-cyclobutene-1,2-dione in absolute EtOH and cat.DMAP is heated using microwave radiation in a Personal Chemistry Emrys™ Optimizer microwave reactor at 120° C. for 1 hour. The solvent is removed in vacuo and the resulting crude product partitioned between ethyl acetate and water. The organic portion is separated, dried (Na2SO4) and concentrated in vacuo. Purification by column chromatography on silica gel eluting with EtOAc/iso-hexane (30-100% EtOAc) affords the titled compound.

Workup

  1. customat 120° C.
  2. customfor 1 hour
  3. customThe solvent is removed in vacuo
  4. customthe resulting crude product partitioned between ethyl acetate and water
  5. customThe organic portion is separated
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customPurification by column chromatography on silica gel eluting with EtOAc/iso-hexane (30-100% EtOAc)

Sources & evidence

ORD record
ord-0cec7c62712a4e4183792629600759f0
Source dataset
uspto-grants-2012_09
Patent number
US08258141B2

Reaction notes

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