HCID 131721924, compound → HCID 131721925, compound

HRID 2269604Notes

Reaction equation

HRID 2269604 reaction equation
[NH:1](C(OC(C)(C)C)=O)[CH2:2][C:3]([N:5]1[CH2:20][CH2:19][CH2:18][C@H:6]1[C:7]([NH:9][C@H:10]([C:15]([NH2:17])=[O:16])[CH2:11][CH2:12][CH2:13][CH3:14])=[O:8])=[O:4]>C(O)(C(F)(F)F)=O.C(Cl)Cl>[NH2:1][CH2:2][C:3]([N:5]1[CH2:20][CH2:19][CH2:18][C@H:6]1[C:7]([NH:9][C@H:10]([C:15]([NH2:17])=[O:16])[CH2:11][CH2:12][CH2:13][CH3:14])=[O:8])=[O:4]

Participants

4

Reactant 1

HCID 131721924HCID 131721924, compound

Product 1

HCID 131721925HCID 131721925, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
0 °C

Procedure

Boc-Gly-Pro-Nleu-NH2 (3.5 g, 0.0089 mol.) was dissolved in a solution of 30% TFA in DCM (50 ml). The solution was stirred for 40 minutes. The DCM and TFA were removed under reduced pressure, and 3×50 ml benzene were added and distilled under reduced pressure to remove trace TFA. The resulting mixture was dissolved in 30 ml methanol and the solution was chilled to 0° C. HCl/dioxane (4N, 10 ml) was added to the solution to transfer the product from TFA salt to HCl salt. Ethyl ether (200 ml) was added to the solution and a precipitation formed. The ether was removed by filtration and a white solid product was obtained (2.9 g, 87%). Analytical RP-HPLC chromatogram, single peak, RT=15.7 min. (5-15% B in 30 min.). FAB-MS, observed (M+H)+=285. 1H-NMR (500 MHz, DMSO-d6, 25° C., assignment by TOCSY) δ8.03 (m, 3H, Gly-NH3), 7.65 (s, C-terminal NH2), 7.46 (s, C-terminal NH2), 7.34 (s, C-terminal NH2), 7.24 (d, C-terminal NH2), 7.08 (s, C-terminal NH2), 6.92 (s, C-terminal NH2), 4.94 (d, Pro-α), 4.76 (m, Pro-α), 4.59 (m, Pro-α), 4.25-3.52 (sets of bands, Nleu-α, Gly-α), 3.52-3.44 (m, Pro-δ), 3.42-2.70 (sets of bands, Gly-α, Nleu-β), 2.36-1.65 (sets of bands, Pro-β, Pro-γ, Nleu-γ), 0.90 (m, Nleu-δ), 0.79 (m, Nleu-δ).

Workup

  1. customThe DCM and TFA were removed under reduced pressure, and 3×50 ml benzene
  2. additionwere added
  3. distillationdistilled under reduced pressure
  4. customto remove trace TFA
  5. dissolutionThe resulting mixture was dissolved in 30 ml methanol
  6. additionHCl/dioxane (4N, 10 ml) was added to the solution
  7. additionEthyl ether (200 ml) was added to the solution
  8. customa precipitation
  9. customformed
  10. customThe ether was removed by filtration
  11. customa white solid product was obtained (2.9 g, 87%)
  12. customAnalytical RP-HPLC chromatogram, single peak, RT=15.7 min. (5-15% B in 30 min.)

Sources & evidence

ORD record
ord-2788b8772cb7430cba11a8b05a3b7d58
Source dataset
uspto-grants-2001_12
Patent number
US06329506B1

Reaction notes

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