Diisopropylethylamine → HCID 67067242, compound

HRID 1009449Notes

Reaction equation

HRID 1009449 reaction equation
C(N(C(C)C)CC)(C)C.[CH3:10][O:11][C:12]1[CH:13]=[C:14](/[CH:24]=[CH:25]/[C:26]([OH:28])=O)[CH:15]=[CH:16][C:17]=1[N:18]1[CH:22]=[C:21]([CH3:23])[N:20]=[CH:19]1.C1N(P(Cl)(N2C(=O)OCC2)=O)C(=O)OC1.Cl.[Cl:45][CH2:46][CH2:47][CH2:48][CH2:49][CH:50]([C:55]1[CH:60]=[C:59]([F:61])[C:58]([F:62])=[C:57]([F:63])[CH:56]=1)[C:51]([NH:53][NH2:54])=O>C(Cl)Cl.O>[Cl:45][CH2:46][CH2:47][CH2:48][CH2:49][CH:50]([C:51]1[O:28][C:26](/[CH:25]=[CH:24]/[C:14]2[CH:15]=[CH:16][C:17]([N:18]3[CH:22]=[C:21]([CH3:23])[N:20]=[CH:19]3)=[C:12]([O:11][CH3:10])[CH:13]=2)=[N:54][N:53]=1)[C:55]1[CH:56]=[C:57]([F:63])[C:58]([F:62])=[C:59]([F:61])[CH:60]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 59528030(E)-3-[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]acrylic acidHCID 67067443HCID 67067443, compound

Product 1

HCID 67067242HCID 67067242, compoundYield 47.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 4 N hydrogen chloride in ethyl acetate (30 mL) was added to tert-butyl N′-[6-chloro-2-(3,4,5-trifluorophenyl)hexanoyl]hydrazinecarboxylate synthesized according to the method described in Examples 112 and 113 (ESI-MS; m/z 417 [M++Na], 2.08 g). The reaction solution was stirred at room temperature for one hour and then concentrated under reduced pressure to obtain 6-chloro-2-(3,4,5-trifluorophenyl)hexanoic acid hydrazide hydrochloride (1.81 g). IPEA (1.5 mL), (E)-3-[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]acrylic acid (450 mg) and BOPCl (0.53 g) were added to a solution of 6-chloro-2-(3,4,5-trifluorophenyl)hexanoic acid hydrazide hydrochloride (612 mg) in methylene chloride (15 mL) at room temperature, and the reaction solution was stirred at room temperature for three hours. Water was added to the reaction solution, followed by extraction with chloroform. The resulting extract was washed with a saturated sodium chloride solution, dried over magnesium sulfate and then concentrated under reduced pressure. A solution of the resulting residue in phosphorus oxychloride (8 mL) was heated under reflux for three hours. The reaction solution was left to cool to room temperature and concentrated under reduced pressure. A saturated sodium bicarbonate solution was added to the resulting residue, followed by extraction with ethyl acetate. The resulting extract was dried over magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (elution solvent: heptane-ethyl acetate system) to obtain 430 mg of the title compound. The property value of the compound is as follows.

Workup

  1. extractionfollowed by extraction with chloroform
  2. extractionThe resulting extract
  3. washwas washed with a saturated sodium chloride solution
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. temperatureA solution of the resulting residue in phosphorus oxychloride (8 mL) was heated
  7. temperatureunder reflux for three hours
  8. waitThe reaction solution was left
  9. temperatureto cool to room temperature
  10. concentrationconcentrated under reduced pressure
  11. additionA saturated sodium bicarbonate solution was added to the resulting residue
  12. extractionfollowed by extraction with ethyl acetate
  13. extractionThe resulting extract
  14. dry with materialwas dried over magnesium sulfate
  15. concentrationconcentrated under reduced pressure
  16. customThe residue was purified by silica gel column chromatography (elution solvent: heptane-ethyl acetate system)

Sources & evidence

ORD record
ord-8260e71be4ca46589e27a4b86d1477df
Source dataset
uspto-grants-2011_07
Patent number
US07973033B2

Reaction notes

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