Reaktion #161968

Reaktionsgleichung

Hunig's base

TFA

#114

methyl N-{(2R,3R)-3-methoxy-3-[(2S)-1-{(3R,4S,5S)-3-methoxy-5-methyl-4-[methyl(L-valyl)amino]heptanoyl}pyrrolidin-2-yl]-2-methylpropanoyl}-L-phenylalaninate

1-(tert-butoxycarbonyl)-2-methyl-D-proline

HATU

→

#131

Ausbeute 54.0%

2-methyl-D-prolyl-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-3-{[(2S)-1-methoxy-1-oxo-3-phenylpropan-2-yl]amino}-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide trifluoroacetic acid salt

Ausbeute 54.0%

Lösungsmittel

dichloromethane

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeReaction
2. 2
   SonstigeReaction
3. 3
   workup.STIRRINGto stir at room temperature for -1 hour
4. 4
   SonstigeReaction
5. 5
   SonstigePurification by (Method J*)

Vorschrift

To a stirring solution of #114 (164 mg, 0.259 mmol, 1.0 eq.) and 1-(tert-butoxycarbonyl)-2-methyl-D-proline (71.3 mg, 0.311 mmol, 1.2 eq.) in 4 mL of dichloromethane, HATU (118 mg, 0.311 mmol, 1.2 eq.) was added followed by Hunig's base (0.180 mL, 1.04 mmol, 4 eq.). The reaction was allowed to stir at room temperature for -30 minutes. Reaction was reduced down. Reaction was taken up in 3.5 mL of dichloromethane and placed under nitrogen. To this stirring solution, TFA (1.5 mL, 20 mmol, 76 eq.) was added. The reaction was allowed to stir at room temperature for -1 hour. Reaction was reduced down and placed underneath high vacuum. Purification by (Method J*) affords #131 (119 mg, 54%) as a white solid. HPLC (Protocol A at 45° C.): m/z 744.5 [M+H+], retention time=7.342 minutes (purity >98%). 1H NMR (400 MHz, DMSO-d6), δ 9.08-9.18 (m), 8.79-8.89 (m), 8.76 (t), 8.54 (d), 8.29 (d), 7.14-7.31 (m), 4.70-4.79 (m), 4.57-4.66 (m), 4.45-4.55 (m), 3.96-4.04 (m), 3.74-3.80, 3.66 (d), 3.48-3.61 (m), 3.40-3.48 (m), 3.09-3.34 (m), 3.00-3.09 (m), 2.95-3.00 (m), 2.83-2.93 (m), 2.36-2.53 (m), 2.21-2.35 (m), 2.10-2.19 (m), 1.99-2.10 (m), 1.61-1.09 (m), 1.36-1.53 (m), 1.21-1.35 (m), 1.02-1.10 (m), 0.94-1.0 (m), 0.86-0.93 (m), 0.73-0.82 (m).

Quelle