Water → HCID 117840702, compound

HRID 714803Notes

Reaction equation

HRID 714803 reaction equation
[CH2:1]([C:3]1([CH2:22][C:23](O)=O)[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]([NH:14][C:15]3[CH:16]=[N:17][N:18]([CH3:20])[CH:19]=3)[N:9]=2)[C:4]1=[O:21])[CH3:2].[NH4+].O[N:28]1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.O>CN(C)C=O>[CH2:1]([C:3]1([CH2:22][C:23]#[N:28])[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]([NH:14][C:15]3[CH:16]=[N:17][N:18]([CH3:20])[CH:19]=3)[N:9]=2)[C:4]1=[O:21])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 220338091-Hydroxybenzotriazole, ammonium saltHCID 117840271HCID 117840271, compound

Product 1

HCID 117840702HCID 117840702, compoundYield 18%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (3-ethyl-1-(2-((1-methyl-H-pyrazol-4-yl)amino)pyrimidin-4-yl)-2-oxopyrrolidin-3-yl)acetic acid (100 mg) obtained in Example 30 and 1-hydroxybenzotriazole ammonium salt (88 mg) in N,N-dimethylformamide (5 mL) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (110 mg), and the mixture was stirred overnight at room temperature. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. To a solution of the residue and pyridine (70 mg) in tetrahydrofuran (5 mL) was added trifluoroacetic anhydride (0.12 mL), and the mixture was stirred at 70° C. for 30 min. The reaction mixture was neutralized with saturated aqueous sodium hydrogen carbonate solution, and extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate), and recrystallized (hexane/ethyl acetate) to give the title compound (17 mg).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe obtained organic layer was washed with water and saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. additionTo a solution of the residue and pyridine (70 mg) in tetrahydrofuran (5 mL) was added trifluoroacetic anhydride (0.12 mL)
  6. stirringthe mixture was stirred at 70° C. for 30 min
  7. extractionextracted with ethyl acetate
  8. washThe obtained organic layer was washed with saturated brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. customthe solvent was evaporated under reduced pressure
  11. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)
  12. customrecrystallized (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-fb3acba354d94070a9bc349396b7b1ee
Source dataset
uspto-grants-2015_11
Patent number
US09187453B2

Reaction notes

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