Hydrochloric Acid → HCID 86705122, compound

HRID 541549Notes

Reaction equation

HRID 541549 reaction equation
[C:1]([O:6][CH2:7]Cl)(=[O:5])[CH2:2][CH2:3][CH3:4].[Na+].[I-].[Cl:11][C:12]1[CH:13]=[CH:14][C:15]([F:59])=[C:16]([C:18]2[CH:23]=[CH:22][C:21]([CH2:24][N:25]([CH2:53][C@@H:54]([OH:58])[C:55]([OH:57])=[O:56])[NH:26][C:27]([C:29]3[N:30]=[N:31][N:32](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[N:33]=3)=[O:28])=[CH:20][CH:19]=2)[CH:17]=1.CCN(C(C)C)C(C)C.Cl.O1CCOCC1.CC#N>CC(C)=O>[Cl:11][C:12]1[CH:13]=[CH:14][C:15]([F:59])=[C:16]([C:18]2[CH:23]=[CH:22][C:21]([CH2:24][N:25]([CH2:53][C@@H:54]([OH:58])[C:55]([O:57][CH2:7][O:6][C:1](=[O:5])[CH2:2][CH2:3][CH3:4])=[O:56])[NH:26][C:27]([C:29]3[N:30]=[N:31][NH:32][N:33]=3)=[O:28])=[CH:20][CH:19]=2)[CH:17]=1

Participants

9

Reactant 7

HCID 313Hydrochloric AcidHCID 5238Sodium IodideHCID 6342AcetonitrileHCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 2725008Chloromethyl butanoateHCID 86705123HCID 86705123, compound

Product 1

HCID 86705122HCID 86705122, compoundYield 13.4%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent2×

Conditions

Temperature
60 °C

Procedure

A mixture of chloromethyl butyrate (6.8 μL, 54.5 μmol) and NaI (8.2 mg, 54.5 μmol) in acetone (0.5 mL, 7 mmol) was stirred at 60° C. for 1 hour, then it was added to a mixture of (R)-3-[N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-(2-trityl-2H-tetrazole-5-carbonyl)hydrazino]-2-hydroxypropionic acid (12.3 mg, 18.2 μmol) and DIPEA (4.8 μL, 27.2 μmol) in acetone (0.5 mL). The resulting mixture was stirred at 40° C. for 2 hours, concentrated and partitioned between EtOAc (10 mL) and water (2 mL). The organic layer was dried over MgSO4, filtered, and concentrated. 4.0 M HCl in 1,4-dioxane (40.0 μL, 160 μmol) in MeCN (0.2 mL, 4 mmol) was added and the resulting mixture was stirred at room temperature for 20 minutes. The mixture was concentrated and the residue was dissolved in AcOH (1.5 mL), filtered, and purified by reverse phase preparative HPLC to yield the title compound (1.3 mg). MS m/z [M+H]+ calc'd for C23H24ClFN6O6, 535.14. found 535.1.

Workup

  1. stirringThe resulting mixture was stirred at 40° C. for 2 hours
  2. concentrationconcentrated
  3. custompartitioned between EtOAc (10 mL) and water (2 mL)
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. stirringthe resulting mixture was stirred at room temperature for 20 minutes
  8. concentrationThe mixture was concentrated
  9. dissolutionthe residue was dissolved in AcOH (1.5 mL)
  10. filtrationfiltered
  11. custompurified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-633ccb30587f46ff86990a9ad60decfe
Source dataset
uspto-grants-2014_10
Patent number
US08871792B2

Reaction notes

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