Reaktion #161925

Reaktionsgleichung

#50

N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-{[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino}propyl]pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide

bromotris(dimethylamino)phosphonium hexafluorophosphate

diisopropylethylamine

1-aminocyclopropanecarboxylic acid

→

#51

Ausbeute 40.5%

N2-[(1-aminocyclopropyl)carbonyl]-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-{[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino}propyl]pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide

Ausbeute 40.5%

Lösungsmittel

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethe mixture was quenched with water
2. 2
   Extraktionextracted twice with ethyl acetate
3. 3
   TrocknenThe combined organic layers were dried over sodium sulfate
4. 4
   Filtrationfiltered
5. 5
   Einengenconcentrated in vacuo
6. 6
   SonstigeThe residue was purified by silica gel chromatography (Gradient: 0% to 5% methanol in dichloromethane)

Vorschrift

To a solution of #50 (100 mg, 0.15 mmol, 1 eq.), bromotris(dimethylamino)phosphonium hexafluorophosphate (Brop, 70 mg, 0.18 mmol, 1.2 eq.) and diisopropylethylamine (0.08 mL, 0.45 mmol, 3 eq.) in dichloromethane (15 mL, 0.01 M) at 0° C. was added 1-aminocyclopropanecarboxylic acid (18 mg, 0.18 mmol, 1.2 eq.). After 2 hours, the mixture was quenched with water and extracted twice with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (Gradient: 0% to 5% methanol in dichloromethane) to give #51 (45 mg, 34%). Rf 0.5 (10% methanol in dichloromethane). LC-MS (Protocol L): m/z 741.44 [M+H+]; 1H NMR (300 MHz, DMSO-d6), presumed to be a mixture of rotamers, characteristic signals: δ [8.64 (br d, J=8 Hz) and 8.88 (br d, J=8 Hz), total 1H], [8.16 (br d, J=9 Hz) and 8.22 (br d, J=10 Hz), total 1H], [7.77 (d, J=3.5 Hz) and 7.79 (d, J=3.5 Hz), total 1H], [7.63 (d, J=3.5 Hz) and 7.65 (d, J=3 Hz), total 1H], 7.10-7.32 (m, 5H), 5.33-5.60 (m, 1H), 3.16, 3.20, 3.21 and 3.26 (4 s, total 6H), 2.93 and 3.02 (2 br s, total 3H), [1.05 (d, J=6.3 Hz) and 1.10 (d, J=6.3 Hz), total 3H].

Quelle