Dichloromethane → HCID 131724422, compound

HRID 2087123Notes

Reaction equation

HRID 2087123 reaction equation
N[C@H](C(N1CCC[C@H]1C(OCC1C=CC=CC=1)=O)=O)C(C)C.N(C(OC(C)(C)C)=O)[C@H](C(O)=O)C(C)C.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.C1CCC(N=C=NC2CCCCC2)CC1.N(C(OCC1C=CC=CC=1)=O)[C@H](C([NH:83][C@H:84]([C:88]([NH:90][C@H:91]([C:95]([N:97]1[CH2:111][CH2:110][CH2:109][C@H:98]1[C:99]([O:101][CH2:102][C:103]1[CH:108]=[CH:107][CH:106]=[CH:105][CH:104]=1)=[O:100])=[O:96])[CH:92]([CH3:94])[CH3:93])=[O:89])[CH:85]([CH3:87])[CH3:86])=O)CCC(=O)OC(C)(C)C.C(Cl)[Cl:123]>>[NH2:83][C@H:84]([C:88]([NH:90][C@H:91]([C:95]([N:97]1[CH2:111][CH2:110][CH2:109][C@H:98]1[C:99]([O:101][CH2:102][C:103]1[CH:108]=[CH:107][CH:106]=[CH:105][CH:104]=1)=[O:100])=[O:96])[CH:92]([CH3:94])[CH3:93])=[O:89])[CH:85]([CH3:87])[CH3:86].[ClH:123]

Participants

8

Reactant 7

HCID 6344DichloromethaneHCID 79724-MethylmorpholineHCID 10868Dicyclohexylcarbodiimide2×HCID 757711-HydroxybenzotriazoleHCID 83693Boc-L-ValineHCID 14304309L-Valyl-L-proline phenylmethyl esterHCID 131724226Z-Glu(OtBu)-Val-Val-Pro-OBzl

Product 1

HCID 131724422HCID 131724422, compoundYield 100%

Procedure

Boc-Val-Val-Pro-OBzl was prepared by dissolving Boc-Val-Pro-OBzl (14.0 g, 35.0 mmol) in 4N HCl in dioxane (20 mL) and allowing the reaction to stir for 2 h under an inert atmosphere at room temperature. The reaction mixture was concentrated by evaporation in vacuo and ether was added to yield a precipitate. It was collected by filtration under nitrogen. After drying in vacuo with P205, H-Val-Pro-OBzl was obtained as a white solid (22.6 g, 30.3 mmol, 89%). (ESI/MS calculated for C17H24N2O3+H: 305.2. Found: 305.2.) H-Val-Pro-OBzl (9.2 g, 27 mmol) was dissolved in 50 mL of CH2Cl2 and Boc-Val-OH (7.3 g, 27 mmol), HOBt (7.3 g, 54 mmol), NMM (3.0 mL, 27 mmol) and DCC (5.6 g, 27 mmol) were added. The reaction mixture stirred overnight at room temperature. The mixture was filtered and the filtrate was evaporated. The residue was dissolved in ethyl acetate and the solution was re-filtered. The filtrate was washed with 0.2N HCl, 5% NaHCO3, and saturated aqueous NaCl. It was dried over Na2SO4, filtered and evaporated to give a yellow oil (10.6 g, 21.1=mol, 78%). ESI/MS calculated for C27H41N3O6+Na: 526.3 Found: 526.4. Z-Glu(OtBu)-Val-Val-Pro-OBzl was also prepared by DCC coupling. H-Val-Val-Pro-OBzl-hydrochloride was obtained in a 100% yield by treating the corresponding Boc compound with anhydrous HCl using the procedure described for H-Val-Pro-OBzl (ESI/MS calculated for C22H33N3O4+H: 404.2. Found 404.3.). The amine hydrochloride (7.40 g, 16.8 mmol) was dissolved in 185 mL DMF and 25 mL THF. Z-Glu(OtBu)—OH (5.60 g, 16.8 mmol), HOBT (4.60 g, 33.6 mmol), NMM (1.85 mL, 16.8 mmol) and DCC (3.5 g, 16.8 mmol) were added. The reaction was run and the product was isolated by the procedure described for Boc-Val-Val-Pro-OBzl. The tetrapeptide was obtained as a white foam (12.0 g, 16.1 mmol, 96%). ESI/MS calculated for C39H54N4O9+Na: 745.4. Found: 745.4.

Workup

  1. filtrationThe mixture was filtered
  2. customthe filtrate was evaporated
  3. dissolutionThe residue was dissolved in ethyl acetate
  4. filtrationthe solution was re-filtered
  5. washThe filtrate was washed with 0.2N HCl, 5% NaHCO3, and saturated aqueous NaCl
  6. dry with materialIt was dried over Na2SO4
  7. filtrationfiltered
  8. customevaporated
  9. customto give a yellow oil (10.6 g, 21.1=mol, 78%)

Sources & evidence

ORD record
ord-6d8f30de9674447b83e86efe7b04eedf
Source dataset
uspto-grants-2004_04
Patent number
US06727366B2

Reaction notes

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