5-Chloro-2-furaldehyde → (8R)-10-(5-chlorofuran-2-yl)-5-(3-fluorophenyl)-8-(hydroxymethyl)-1,3-dimethyl-7,8-dihydro-1H-pyrimido[4',5':3,4]pyrrolo[2,1-c][1,4]oxazine-2,4(3H,10H)-dione

HRID 624559Notes

Reaction equation

HRID 624559 reaction equation
[OH:1][C@@H:2]([CH2:24][OH:25])[CH2:3][N:4]1[C:12]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[CH:14]=2)=[C:11]2[C:6]([N:7]([CH3:23])[C:8](=[O:22])[N:9]([CH3:21])[C:10]2=[O:20])=[CH:5]1.[O-]S(C(F)(F)F)(=O)=O.[Bi+3].[O-]S(C(F)(F)F)(=O)=O.[O-]S(C(F)(F)F)(=O)=O.[Cl:51][C:52]1[O:56][C:55]([CH:57]=O)=[CH:54][CH:53]=1>C(O)C>[Cl:51][C:52]1[O:56][C:55]([CH:57]2[C:5]3=[C:6]4[N:7]([CH3:23])[C:8](=[O:22])[N:9]([CH3:21])[C:10](=[O:20])[C:11]4=[C:12]([C:13]4[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[CH:14]=4)[N:4]3[CH2:3][C@H:2]([CH2:24][OH:25])[O:1]2)=[CH:54][CH:53]=1

Participants

5

Reactant 3

HCID 27696305-Chloro-2-furaldehydeHCID 9917655Bi(OTf)3HCID 86722881(R)-6-(2,3-Dihydroxypropyl)-5-(3-fluorophenyl)-1,3-dimethyl-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione

Product 1

HCID 86722883(8R)-10-(5-chlorofuran-2-yl)-5-(3-fluorophenyl)-8-(hydroxymethyl)-1,3-dimethyl-7,8-dihydro-1H-pyrimido[4',5':3,4]pyrrolo[2,1-c][1,4]oxazine-2,4(3H,10H)-dione

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (R)-6-(2,3-dihydroxypropyl)-5-(3-fluorophenyl)-1,3-dimethyl-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione (step 2) (806 mg, 2.320 mmol), bismuth triflate (305 mg, 0.464 mmol) and 5-chlorofuran-2-carbaldehyde (commercial) (333 mg, 2.55 mmol) in ethanol (13.6 mL) was heated under microwave irradiation at 100° C. for 25 mins. The mixture was evaporated under vacuum. The residue was partitioned between 0.1 M HCl (50 mL) and DCM (100 mL) and extracted with DCM (3×100 mL). The combined organic extracts were dried over magnesium sulfate and evaporated under vacuum. Purification by chromatography on silica, eluting with 0-60% EtOAc/hexane afforded the title compound as a mixture of diastereomers.

Workup

  1. customThe mixture was evaporated under vacuum
  2. customThe residue was partitioned between 0.1 M HCl (50 mL) and DCM (100 mL)
  3. extractionextracted with DCM (3×100 mL)
  4. dry with materialThe combined organic extracts were dried over magnesium sulfate
  5. customevaporated under vacuum
  6. customPurification by chromatography on silica
  7. washeluting with 0-60% EtOAc/hexane

Sources & evidence

ORD record
ord-9b62974f7daf4c65bcc38420fc179238
Source dataset
uspto-grants-2016_04
Patent number
US09303035B2

Reaction notes

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