Lithium Hydroxide → (S)-2-(4-aminomethyl-2,6-difluorobenzoylamino)-3-[4-(1,3,6-trimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)phenyl]propionic acid

HRID 63748Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 63748
C([O:4][C:5](=[O:38])[C@@H:6]([NH:25][C:26](=[O:37])[C:27]1[C:32]([F:33])=[CH:31][C:30]([CH2:34][NH2:35])=[CH:29][C:28]=1[F:36])[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:15](=[O:24])[N:16]([CH3:23])[C:17](=[O:22])[N:18]([CH3:21])[C:19]=2[CH3:20])=[CH:10][CH:9]=1)CC.[OH-].[Li+].C(O)(C(F)(F)F)=O>C1COCC1.O>[NH2:35][CH2:34][C:30]1[CH:29]=[C:28]([F:36])[C:27]([C:26]([NH:25][C@@H:6]([CH2:7][C:8]2[CH:9]=[CH:10][C:11]([C:14]3[C:15](=[O:24])[N:16]([CH3:23])[C:17](=[O:22])[N:18]([CH3:21])[C:19]=3[CH3:20])=[CH:12][CH:13]=2)[C:5]([OH:38])=[O:4])=[O:37])=[C:32]([F:33])[CH:31]=1

Komponenten

6

Edukt 3

HCID 3939Lithium HydroxideHCID 6422Trifluoroacetic acidHCID 86691355(S)-2-(4-aminomethyl-2,6-difluorobenzoylamino)-3-[4-(1,3,6-trimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)phenyl]propionic acid propyl ester

Produkt 1

HCID 86691354(S)-2-(4-aminomethyl-2,6-difluorobenzoylamino)-3-[4-(1,3,6-trimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)phenyl]propionic acidAusbeute 96,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a suspension of (S)-2-(4-aminomethyl-2,6-difluorobenzoylamino)-3-[4-(1,3,6-trimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)phenyl]propionic acid propyl ester (508 mg, 0.96 mmol) in THF (10 mL) was added a solution of lithium hydroxide (240 mg, 10 mmol) in water (2 mL) at room temperature. The mixture was stirred for 15 h at which time TLC analysis indicated the absence of starting material. Then, the THF was removed under reduced pressure and the residue was diluted with water (100 mL) and the mixture was acidified with TFA. The crude product was purified by HPLC to afford 450 mg (78% yield) of (S)-2-(4-aminomethyl-2,6-difluorobenzoylamino)-3-[4-(1,3,6-trimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)phenyl]propionic acid as a TFA salt as a white solid. ES-LRMS m/e calcd for C24H24F2N4O5 (M+H)+ 487, found 487.

Aufarbeitung

  1. customThen, the THF was removed under reduced pressure
  2. additionthe residue was diluted with water (100 mL)
  3. customThe crude product was purified by HPLC

Quellen und Nachweise

ORD-Eintrag
ord-87b410a735684971b6d7dd97f7954313
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09447035B2

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