Oxalyl chloride → 5-(1,1-Dimethylethyl) 1-ethyl 4,6-dihydro-3-[[2-(2-naphthalenyl)-1-oxopropyl]amino]pyrrolo[3,4-c]pyrazole-1,5-dicarboxylate

HRID 1982756Notes

Reaction equation

HRID 1982756 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH:11]([CH3:15])[C:12]([OH:14])=O.C(Cl)(C(Cl)=O)=O.[CH2:22]([O:24][C:25]([N:27]1[C:31]2[CH2:32][N:33]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:34][C:30]=2[C:29]([NH2:42])=[N:28]1)=[O:26])[CH3:23].CCN(C(C)C)C(C)C>C(Cl)Cl.CN(C=O)C.C1COCC1.C(OCC)(=O)C.C1CCCCC1>[CH2:22]([O:24][C:25]([N:27]1[C:31]2[CH2:32][N:33]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:34][C:30]=2[C:29]([NH:42][C:12](=[O:14])[CH:11]([C:2]2[CH:3]=[CH:4][C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[CH:1]=2)[CH3:15])=[N:28]1)=[O:26])[CH3:23]

Participants

9

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 69190455-tert-Butyl 1-ethyl 3-amino-4,6-dihydropyrrolo[3,4-c]pyrazole-1,5-dicarboxylateHCID 1314784613350-60-2

Product 1

HCID 684415245-(1,1-Dimethylethyl) 1-ethyl 4,6-dihydro-3-[[2-(2-naphthalenyl)-1-oxopropyl]amino]pyrrolo[3,4-c]pyrazole-1,5-dicarboxylateYield 93%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent2×HCID 21867204Cyclohexane ethylacetateSolvent

Procedure

To a solution of 2-naphthalen-2-yl-propionic acid (1.48 g. 7.4 mmol) in DCM (40 ml) and DMF cat., (COCl)2 (0.83 ml, 9.65 mmol) in DCM (10 ml) was added dropwise. The mixture was stirred at r.t. for 30 min. The reaction mixture was concentrated under vacuum, reconstituted twice with toluene and concentrated. A solution of the obtained acyl-chloride in THF (40 ml) was added slowly to a mixture of 3-amino-4,6-dihydro-pyrrolo[3,4-c]pyrazole-1,5-dicarboxylic acid 5-tert-butyl ester 1-ethyl ester (2.0 g, 6.75 mmol) and DIEA (5.8 ml, 33.3 mmol) in THF (40 ml) at 0-5° C. The reaction was allowed to reach r.t. and stirred overnight. The mixture was filtered and the solution evaporated to dryness under vacuum. The resulting residue was dissolved in DCM and the obtained solution was washed with brine, dried over sodium sulfate, filtered and evaporated to dryness. The crude product was purified by flash-chromatography (eluent:ethyl acetate/cyclohexane 3/7 then 4/6) to give 3.0 g (93% yield) of the title compound as a white solid.

Workup

  1. concentrationThe reaction mixture was concentrated under vacuum
  2. concentrationconcentrated
  3. customto reach r.t.
  4. stirringstirred overnight
  5. filtrationThe mixture was filtered
  6. customthe solution evaporated to dryness under vacuum
  7. dissolutionThe resulting residue was dissolved in DCM
  8. washthe obtained solution was washed with brine
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. customevaporated to dryness
  12. customThe crude product was purified by flash-chromatography (eluent

Sources & evidence

ORD record
ord-03c59ebf47294017877d142b189c3983
Source dataset
uspto-grants-2009_06
Patent number
US07541354B2

Reaction notes

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