L-Pyroglutamic Acid → HCID 10300009, compound

HRID 989676Notes

Reaction equation

HRID 989676 reaction equation
[NH:1]1[C:5](=[O:6])[CH2:4][CH2:3][C@H:2]1[C:7]([OH:9])=O.S(Cl)(Cl)=O.Cl.NC(CS)C[N:18]1[C:24]2[CH:25]=[CH:26][C:27]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[CH:28][C:23]=2[CH2:22][N:21]([C:35]([C:37]2[C:46]3[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=3)[CH:40]=[CH:39][CH:38]=2)=[O:36])[CH2:20][CH2:19]1.C(N(C(C)C)CC)(C)C>C(Cl)Cl.N1C=CC=CC=1>[C:37]1([C:35]([N:21]2[CH2:22][C:23]3[CH:28]=[C:27]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)[CH:26]=[CH:25][C:24]=3[N:18]([C:7]([CH:2]3[CH2:3][CH2:4][C:5](=[O:6])[NH:1]3)=[O:9])[CH2:19][CH2:20]2)=[O:36])[C:46]2[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=2)[CH:40]=[CH:39][CH:38]=1

Participants

7

Reactant 4

HCID 7405L-Pyroglutamic AcidHCID 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 131723531HCID 131723531, compound

Product 1

HCID 10300009HCID 10300009, compoundYield 28.9%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of pyroglutamic acid (400 mg, 3.1 mmol) in methylene chloride (6 mL), was added thionyl chloride (4 mL) along with a drop of pyridine at room temperature. The reaction mixture was allowed to stir for 2 h and concentrated. The residue was dissolved in 2 mL methylene chloride. To this stirred solution, was added the compound E of Example 2 (40 mg, 0.106 mmol) and diisopropylethylamine (0.5 mL, 3 mmol) in methylene chloride (5 mL). The mixture was allowed to stir for 16 h, and concentrated. The residue was dissolved in ethyl acetate (50 mL). The resultant solution was washed successively with 1N aqueous potassium bisulfate, saturated aqueous sodium bicarbonate and brine. The organic layer was dried (MgSO4), filtered and concentrated. The residue was purified by preparative HPLC (aqueous methanol with 0.1% TFA) to give 15 mg of the title compound as a white solid. MS (M+NH4): 507.

Workup

  1. concentrationconcentrated
  2. dissolutionThe residue was dissolved in 2 mL methylene chloride
  3. stirringto stir for 16 h
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in ethyl acetate (50 mL)
  6. washThe resultant solution was washed successively with 1N aqueous potassium bisulfate, saturated aqueous sodium bicarbonate and brine
  7. dry with materialThe organic layer was dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by preparative HPLC (aqueous methanol with 0.1% TFA)

Sources & evidence

ORD record
ord-2a1b512b73a54264961839897bfb9edb
Source dataset
uspto-grants-2002_10
Patent number
US06458783B1

Reaction notes

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