Reaktion #610567

Reaktionsgleichung

DIPEA

(2S,4S)-5-Biphenyl-4-yl-4-t-butoxycarbonylamino-2-hydroxymethyl-pentanoic acid

DIPEA

1,2,3-triazole-4-carboxylic acid

HATU

1-chloroethyl cyclohexyl carbonate

→

title compound

Ausbeute 95.0%

(2S,4S)-5-Biphenyl-4-yl-2-hydroxymethyl-4-[(3H-[1,2,3]triazole-4-carbonyl)-amino]-pentanoic acid 1-cyclohexyloxycarbonyloxy-ethyl ester

Ausbeute 95.0%

Lösungsmittel

DMA

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe reaction vessel was capped
2. 2
   Sonstigemicrowaved at 80° C. for 2 hours
3. 3
   SonstigeThe mixture was dried under vacuum
4. 4
   workup.DISSOLUTIONdissolved in MeCN (2 mL)
5. 5
   FiltrationThe precipitate was filtered
6. 6
   workup.ADDITIONthe filtrate containing the intermediate
7. 7
   Einengenwas concentrated down
8. 8
   workup.STIRRINGthe resulting solution was stirred for 5 minutes
9. 9
   workup.STIRRINGThe mixture was stirred for 5 minutes
10. 10
    SonstigeThe reaction was quenched with water
11. 11
    Sonstigethe product dried under vacuum
12. 12
    SonstigeThe product was then purified by preparative HPLC

Vorschrift

(2S,4S)-5-Biphenyl-4-yl-4-t-butoxycarbonylamino-2-hydroxymethyl-pentanoic acid (50 mg, 120 μmol, 1.0 eq.), DMA (1 mL), DIPEA (0.13 mL, 0.75 mmol) and 1-chloroethyl cyclohexyl carbonate (52 mg, 250 μmol, 2.0 eq.) were combined. The reaction vessel was capped and microwaved at 80° C. for 2 hours. The mixture was dried under vacuum, dissolved in MeCN (2 mL), and combined with 4 M of HCl in dioxane (500 μL). The resulting mixture was stirred at room temperature for 30 minutes. The precipitate was filtered and discarded, and the filtrate containing the intermediate was concentrated down and submitted to next step. 1,2,3-triazole-4-carboxylic acid (14 mg, 120 μmol, 0.5 eq.) and HATU (48 mg, 120 μmol, 1.0 eq) were dissolved in DMF (1 mL) and the resulting solution was stirred for 5 minutes, followed by the addition of DIPEA (44 μL) and the intermediate from last step. The mixture was stirred for 5 minutes. The reaction was quenched with water and the product dried under vacuum. The product was then purified by preparative HPLC to yield the title compound (4.8 mg, 95% purity). MS m/z [M+H]+ calc'd for C30H36N4O7, 565.26. found 565.4.

Quelle