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

HRID 1882636Notes

Reaction equation

HRID 1882636 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-75def54603b74b9d90f31c68701e6b76
Source dataset
uspto-grants-2012_11
Patent number
US08318750B2

Reaction notes

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