Acetic Acid → HCID 86586480, compound

HRID 992413Notes

Reaction equation

HRID 992413 reaction equation
[C:1]1([C:7]2[N:8]=[C:9]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([CH2:24][C@H:25]([NH:30][C:31]4[C:34](=[O:35])[C:33](=[O:36])[C:32]=4OC(C)C)[C:26]([O:28]C)=[O:27])=[CH:20][CH:19]=3)[C:10]3[C:15]([CH:16]=2)=[CH:14][CH:13]=[CH:12][CH:11]=3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH:41]1[CH2:46][CH2:45][O:44][CH2:43][CH2:42]1.C(O)(=O)C>CO>[C:1]1([C:7]2[N:8]=[C:9]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([CH2:24][C@H:25]([NH:30][C:31]4[C:34](=[O:35])[C:33](=[O:36])[C:32]=4[N:41]4[CH2:46][CH2:45][O:44][CH2:43][CH2:42]4)[C:26]([OH:28])=[O:27])=[CH:20][CH:19]=3)[C:10]3[C:15]([CH:16]=2)=[CH:14][CH:13]=[CH:12][CH:11]=3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 8083MorpholineHCID 86586481HCID 86586481, compound

Product 1

HCID 86586480HCID 86586480, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of methyl (S)-3-[4-(3-phenyl-1-isoquinolinylamino)phenyl]-2-(2-isopropoxy-3,4-dioxocyclobut-1-enylamino)propanoate (20 mg, 0.08 mmol) [prepared in a similar manner to the compound of Example 1]in MeOH (0.2 ml) was treated with morpholine (0.011 ml, 0.12 mmol) and the resulting mixture heated at 60° for 24 h. The mixture was concentrated to dryness then redissolved in anhydrous THF (1.0 ml) and treated with polystyrene methylisocyanate resin (Argonaut Technologies, 120 mg, 2.0 mmol/g, 0.24 mmol) at room temperature for 24 h. The resulting mixture was filtered, and the resin was washed with MeOH(1.0 ml). The combined filtrate was evaporated to dryness then redissolved in THF (0.2 ml) and treated with an aqueous solution of lithium hydroxide monohydrate (0.2 ml of a solution of 100 mg in 4.0 ml water, 0.12 mmol) at room temperature for 24 h. The reaction mixture was quenched with glacial acetic acid (0.007 ml, 0.12 mmol), then evaporated to dryness to give the crude product which was purified by preparative HPLC to afford the title compound.

Workup

  1. temperaturethe resulting mixture heated at 60° for 24 h
  2. concentrationThe mixture was concentrated to dryness
  3. dissolutionthen redissolved in anhydrous THF (1.0 ml)
  4. filtrationThe resulting mixture was filtered
  5. washthe resin was washed with MeOH(1.0 ml)
  6. customThe combined filtrate was evaporated to dryness
  7. dissolutionthen redissolved in THF (0.2 ml)
  8. additiontreated with an aqueous solution of lithium hydroxide monohydrate (0.2 ml of a solution of 100 mg in 4.0 ml water, 0.12 mmol) at room temperature for 24 h
  9. customevaporated to dryness
  10. customto give the crude product which
  11. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-434e5bec7c624923b92cd39f7947f044
Source dataset
uspto-grants-2002_10
Patent number
US06469025B1

Reaction notes

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