2,4,6-Trimethylpyridine → (S)-tert-butyl 2-(4-chlorophenyl)-3-(isoquinolin-6-ylamino)-3-oxopropylcarbamate

HRID 1482737Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1482737
[C:1]([O:5][C:6]([NH:8][CH2:9][C@H:10]([C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=1)[C:11]([OH:13])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC1C=C(C)C=C(C)N=1.ClC(OC(C)(C)C(Cl)(Cl)Cl)=O.[NH2:41][C:42]1[CH:43]=[C:44]2[C:49](=[CH:50][CH:51]=1)[CH:48]=[N:47][CH:46]=[CH:45]2.C([O-])(O)=O.[Na+]>CN(C=O)C>[Cl:20][C:17]1[CH:18]=[CH:19][C:14]([C@H:10]([C:11]([NH:41][C:42]2[CH:43]=[C:44]3[C:49](=[CH:50][CH:51]=2)[CH:48]=[N:47][CH:46]=[CH:45]3)=[O:13])[CH2:9][NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[CH:15][CH:16]=1

Komponenten

7

Edukt 5

HCID 79532,4,6-TrimethylpyridineHCID 516892Sodium BicarbonateHCID 5889916-AminoisoquinolineHCID 51066062,2,2-Trichloro-tert-butyl chloroformateHCID 29947824HCID 29947824, Verbindung

Produkt 1

HCID 90412140(S)-tert-butyl 2-(4-chlorophenyl)-3-(isoquinolin-6-ylamino)-3-oxopropylcarbamate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel3×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To (S)-3-(tert-butoxycarbonylamino)-2-(4-chlorophenyl)propanoic acid (28) (8.5 g, 28.4 mmol) in DMF cooled to 0° C. was added 2,4,6-trimethylpyridine and 2,2,2-trichloro-1,1-dimethylethyl chloroformate in DMF. Then, 6-aminoisoquinoline in DMF was added and the solution stirred for 2 h at 0° C. The mixture was poured into NaHCO3 (sat) and extracted with EtOAc. The organic layers were washed with H2O, dried (Na2SO4), filtered and evaporated to give crude 29. Column chromatography (30% EtOAc-Hexanes) and recrystallization (EtOAc/Hexanes) gave pure (S)-tert-butyl 2-(4-chlorophenyl)-3-(isoquinolin-6-ylamino)-3-oxopropylcarbamate (29, 7.8 g, 64%, >99% S enantiomer).

Aufarbeitung

  1. extractionextracted with EtOAc
  2. washThe organic layers were washed with H2O
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated
  6. customto give crude 29
  7. customColumn chromatography (30% EtOAc-Hexanes) and recrystallization (EtOAc/Hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-68c478e9f6394efbafce932177535957
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09415043B2

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