1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 16739183, compound

HRID 1436144Notes

Reaction equation

HRID 1436144 reaction equation
CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.Cl.Cl[CH2:33][C@@H:34]([CH3:54])[CH2:35]/[C:36](=[CH:40]\[C:41]1[CH:46]=[CH:45][C:44]([N:47]2[CH:51]=[C:50]([CH3:52])[N:49]=[CH:48]2)=[C:43]([F:53])[CH:42]=1)/[C:37]([OH:39])=O.Cl.[NH2:56][C@H:57]([C:61]1[CH:66]=[C:65]([F:67])[C:64]([F:68])=[C:63]([F:69])[CH:62]=1)[C@H:58]([OH:60])[CH3:59]>CN(C=O)C.C(OCC)(=O)C>[F:53][C:43]1[CH:42]=[C:41](/[CH:40]=[C:36]2/[C:37](=[O:39])[N:56]([C@H:57]([C:61]3[CH:62]=[C:63]([F:69])[C:64]([F:68])=[C:65]([F:67])[CH:66]=3)[C@H:58]([OH:60])[CH3:59])[CH2:33][C@@H:34]([CH3:54])[CH2:35]/2)[CH:46]=[CH:45][C:44]=1[N:47]1[CH:51]=[C:50]([CH3:52])[N:49]=[CH:48]1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 68718335(1R,2R)-1-amino-1-(3,4,5-trifluorophenyl)propan-2-ol hydrochlorideHCID 69004927HCID 69004927, compound

Product 1

HCID 16739183HCID 16739183, compoundYield 53.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

DIEA (0.47 mL), WSC (257 mg), and HOBT (181 mg) were added to a suspension of (E)-(S)-5-chloro-2-{1-[3-fluoro-4-(4-methyl-1H-imidazol-1-yl)phenyl]methylidene}-4-methylvaleric acid hydrochloride (250 mg) and (1R,2R)-1-amino-1-(3,4,5-trifluorophenyl)propan-2-ol hydrochloride (243 mg) in DMF (5 mL) at room temperature, and the reaction solution was stirred at room temperature for one hour. Ethyl acetate was added to the reaction solution, which was then sequentially washed with saturated sodium bicarbonate water, water, a saturated ammonium chloride solution, and brine. The resulting organic layer was dried over magnesium sulfate and then concentrated under reduced pressure. The residue was dissolved DMF (8 mL). 60% sodium hydride (32 mg) was added at 0° C., and the reaction solution was stirred at 0° C. for one hour. Ethyl acetate was added to the reaction solution, which was then sequentially washed with saturated sodium bicarbonate water, water, a saturated ammonium chloride solution, and brine. The resulting organic layer was dried over magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (carrier: Chromatorex NH; elution solvent: heptane-ethyl acetate system->ethyl acetate-methanol system) to obtain 176 mg of the title compound. The property values of the compound are as follows.

Workup

  1. washwas then sequentially washed with saturated sodium bicarbonate water, water
  2. dry with materialThe resulting organic layer was dried over magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe residue was dissolved DMF (8 mL)
  5. addition60% sodium hydride (32 mg) was added at 0° C.
  6. stirringthe reaction solution was stirred at 0° C. for one hour
  7. additionEthyl acetate was added to the reaction solution, which
  8. washwas then sequentially washed with saturated sodium bicarbonate water, water
  9. dry with materialThe resulting organic layer was dried over magnesium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by silica gel column chromatography (carrier: Chromatorex NH; elution solvent: heptane-ethyl acetate system->ethyl acetate-methanol system)

Sources & evidence

ORD record
ord-bd12aad82abd4ee48afcb9f6741cd2a0
Source dataset
uspto-grants-2009_11
Patent number
US07618960B2

Reaction notes

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