Cyclopropylamine → 4-[(R)-[[4-[5-[(Cyclopropylamino)carbonyl]-2-methylphenyl]-3,4-dihydro-3-oxopyrazinyl]amino]phenylmethyl]-1-piperidinecarboxylic acid, phenylmethyl ester

HRID 337025Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 337025
CO[C:3](=[O:20])[C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[C:6]([N:11]2[CH:16]=[C:15](Br)[N:14]=[C:13](Br)[C:12]2=[O:19])[CH:5]=1.[C:21]1([CH2:27][O:28][C:29]([N:31]2[CH2:36][CH2:35][CH:34]([C@@H:37]([NH2:44])[C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[CH2:33][CH2:32]2)=[O:30])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[CH:45]1([NH2:48])[CH2:47][CH2:46]1.C1([Mg]Br)CCCC1.C([O-])=O.[NH4+]>C1COCC1.[Pd].C(O)C.C(N(CC)CC)C>[CH:45]1([NH:48][C:3]([C:4]2[CH:9]=[CH:8][C:7]([CH3:10])=[C:6]([N:11]3[CH:16]=[CH:15][N:14]=[C:13]([NH:44][C@@H:37]([C:38]4[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=4)[CH:34]4[CH2:33][CH2:32][N:31]([C:29]([O:28][CH2:27][C:21]5[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=5)=[O:30])[CH2:36][CH2:35]4)[C:12]3=[O:19])[CH:5]=2)=[O:20])[CH2:47][CH2:46]1

Komponenten

10

Edukt 5

HCID 69828CyclopropylamineHCID 2723923Ammonium formateHCID 66688740methyl 3-(3,5-dibromo-2-oxopyrazin-1(2H)-yl)-4-methylbenzoateHCID 666897524-[(R)-aminophenylmethyl]-1-piperidinecarboxylic acid phenylmethyl esterHCID 178419650HCID 178419650, Verbindung

Produkt 1

HCID 666864344-[(R)-[[4-[5-[(Cyclopropylamino)carbonyl]-2-methylphenyl]-3,4-dihydro-3-oxopyrazinyl]amino]phenylmethyl]-1-piperidinecarboxylic acid, phenylmethyl ester

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 23938PalladiumKatalysatorHCID 702EthanolLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 8471TriethylamineLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

To a stirred solution of 3-(3,5-dibromo-2-oxo-2H-pyrazin-1-yl)-4-methyl-benzoic acid methyl ester (Example 1b, 0.1 g) in anhydrous THF (2 mL) within a microwave vial was added triethylamine (100 μL) and 4-[(R)-aminophenylmethyl]-1-piperidinecarboxylic acid phenylmethyl ester (Example 101b, 98 mg). The reaction was heated within a microwave at 120° C. for 60 minutes before cooling to room temperature and adding cyclopropylamine (150 μL) and cyclopentylmagnesium bromide (2M in diethyl ether, 0.75 mL) portionwise After stirring for 30 minutes, ethanol (2 mL) was added followed by the addition of ammonium formate (0.3 g) and 10% palladium on carbon (30 mg). The mixture was heated within a microwave for 180 minutes at 100° C. before being cooled to room temperature, filtered and washed with ethanol. The filtrate was concentrated in vacuo. Purification by preparative HPLC (Gemini column, 0.1% ammonia:acetonitrile eluent) afforded the title compound (19 mg).

Aufarbeitung

  1. temperaturebefore cooling to room temperature
  2. temperatureThe mixture was heated within a microwave for 180 minutes at 100° C.
  3. temperaturebefore being cooled to room temperature
  4. filtrationfiltered
  5. washwashed with ethanol
  6. concentrationThe filtrate was concentrated in vacuo
  7. customPurification by preparative HPLC (Gemini column, 0.1% ammonia:acetonitrile eluent)

Quellen und Nachweise

ORD-Eintrag
ord-12fbd2caa96c42e990e225c253c3b87b
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08889692B2

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