Reaktion #427326

Reaktionsgleichung

DIPEA

O-(benzotriazol-1yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate

(R)-5-methyl-4-(piperidin-4-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine

(S)-2-((S)-1-(tert-butoxycarbonyl)-5,5-dimethylpyrrolidin-2-yl)-2-(4-chlorophenyl)acetic acid

→

(S)-tert-butyl 5-((S)-1-(4-chlorophenyl)-2-(4-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperidin-1-yl)-2-oxoethyl)-2,2-dimethylpyrrolidine-1-carboxylate

Ausbeute 84.9%

Lösungsmittel

DCM

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe reaction was quenched with saturated NH4Cl
2. 2
   Extraktionextracted with DCM (2×10 mL)
3. 3
   TrocknenThe combined organics were dried (Na2SO4)
4. 4
   Filtrationfiltered
5. 5
   Einengenconcentrated
6. 6
   SonstigeThe crude product was purified by flash chromatography (0-5% MeOH/DCM gradient elution)

Vorschrift

DIPEA (174 μL, 1.00 mmol) and O-(benzotriazol-1yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (25 mg, 0.065 mmol) were added to a solution of (R)-5-methyl-4-(piperidin-4-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine (22 mg, 0.10 mmol) and (S)-2-((S)-1-(tert-butoxycarbonyl)-5,5-dimethylpyrrolidin-2-yl)-2-(4-chlorophenyl)acetic acid (20 mg, 0.054 mmol) in DCM (2 mL). The mixture was stirred at room temperature for 2 hours. The reaction was quenched with saturated NH4Cl and extracted with DCM (2×10 mL). The combined organics were dried (Na2SO4), filtered and concentrated. The crude product was purified by flash chromatography (0-5% MeOH/DCM gradient elution) to give (S)-tert-butyl 5-((S)-1-(4-chlorophenyl)-2-(4-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperidin-1-yl)-2-oxoethyl)-2,2-dimethylpyrrolidine-1-carboxylate as a solid (26 mg, 84%). 1H NMR. (CD3OD, 500 MHz) δ 8.73 (s, 3H), 7.42 (d, J=8.5 Hz, 2H), 7.25 (d, J=8.5 Hz, 2H), 4.73-4.70 (m, 2H), 4.40-4.35 (m, 1H), 3.89-3.86 (m, 1H), 3.76-3.70 (m, 2H), 3.49-3.43 (m, 1H), 3.25-3.20 (m, 2H), 3.18-2.97 (m, 2H), 2.86-2.70 (m, 3H), 2.34-2.25 (m, 1H), 2.16-2.13 (m, 1H), 1.83-1.67 (m, 2H), 1.54 (s, 9H), 1.38 (s, 3H), 1.36 (s, 3H), 1.25-1.20 (m, 3H).

Quelle