Trifluoroacetic acid → HCID 131717765, compound

HRID 2082221Notes

Reaction equation

HRID 2082221 reaction equation
N(C(OC(C)(C)C)=O)[C@H](C(N(CC1C=CC=CC=1)CC)=O)[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[C:29]1(OC)[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.[C:37](O)([C:39](F)(F)F)=[O:38].[NH:44]([C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])[C@@H:45]([C:58](O)=[O:59])[CH2:46][C:47]1[C:55]2[C:50](=[CH:51][CH:52]=[CH:53][CH:54]=2)[N:49]([CH:56]=[O:57])[CH:48]=1.C1C=CC2N(O)N=[N:74]C=2C=1.[CH3:78][CH2:79][N:80]=[C:81]=NCCCN(C)C.Cl>C(Cl)Cl>[NH:44]([C:61]([O:63][C:64]([CH3:67])([CH3:65])[CH3:66])=[O:62])[C@@H:45]([C:58]([NH:74][C@H:39]([C:37]([N:80]([CH2:81][C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)[CH2:79][CH3:78])=[O:38])[CH2:3][C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1)=[O:59])[CH2:46][C:47]1[C:55]2[C:50](=[CH:51][CH:52]=[CH:53][CH:54]=2)[N:49]([CH:56]=[O:57])[CH:48]=1

Participants

8

Reactant 6

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 7021874Boc-D-Trp(For)-OHHCID 131717766HCID 131717766, compound

Product 1

HCID 131717765HCID 131717765, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To an ice-cooled solution of Boc-Phe-NEtBzl (3.95 g) and anisole (4 ml) in methylene chloride (16 ml) was added TFA (16 ml). The solution was stirred for an hour at room temperature. After evaporation, addition and re-evaporation of 4N-HCl/DOX (5 ml) were repeated twice. The residue was dissolved in DMF (40 ml), and the solution was ice-cooled and neutralized with triethylamine (1.39 ml). To the solution containing H-Phe-NEtBzl obtained was added Boc-D-Trp(CHO)-OH (3.32 g), HOBT (1.35 g) and WSC.HCl (1.92 g). The solution was stirred for one and half an hour at room temperature. After evaporation and extraction with ethyl acetate. The organic layer was washed successively with water, 2% hydrochloric acid, water, 2% sodium hydrogencarbonate, water and saturated sodium chloride and dried over magnesium sulfate. The evaporated residue was subjected to column chromatography on silica gel (200 g) and eluted with a mixture of chloroform and methanol (50:1 to 20:1, gradient elution). The fractions containing the object compound were combined and evaporated. The residue were pulverized with n-hexane, collected by filtration, washed with n-hexane and dried to give Boc-D-Trp(CHO)-Phe-NEtBzl (4.47 g).

Workup

  1. customAfter evaporation, addition and re-evaporation of 4N-HCl/
  2. dissolutionThe residue was dissolved in DMF (40 ml)
  3. temperaturecooled
  4. additionTo the solution containing H-Phe-NEtBzl
  5. customobtained
  6. stirringThe solution was stirred for one and half an hour at room temperature
  7. customAfter evaporation and extraction with ethyl acetate
  8. washThe organic layer was washed successively with water, 2% hydrochloric acid, water, 2% sodium hydrogencarbonate, water and saturated sodium chloride
  9. dry with materialdried over magnesium sulfate
  10. washeluted with a mixture of chloroform and methanol (50:1 to 20:1, gradient elution)
  11. additionThe fractions containing the object compound
  12. customevaporated
  13. filtrationcollected by filtration
  14. washwashed with n-hexane
  15. customdried

Sources & evidence

ORD record
ord-1d097c52f8114f71b3b0bf284333c5e9
Source dataset
uspto-grants-1993_02
Patent number
US05187156

Reaction notes

Loading…