Hippuric Acid → Telotristat Etiprate

HRID 215939

Reaktionsgleichung

Reaktionsgleichung von HRID 215939
[NH2:1][C@@H:2]([CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[C:19]([O:21][C@H:22]([C:27]3[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][C:28]=3[N:34]3[CH:38]=[CH:37][C:36]([CH3:39])=[N:35]3)[C:23]([F:26])([F:25])[F:24])[N:18]=[C:17]([NH2:40])[N:16]=2)=[CH:11][CH:10]=1)[C:3]([O:5][CH2:6][CH3:7])=[O:4].[C:41]([OH:53])(=[O:52])[CH2:42][NH:43][C:44]([C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)=[O:45]>CCO>[C:41]([OH:53])(=[O:52])[CH2:42][NH:43][C:44]([C:46]1[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=1)=[O:45].[NH2:1][C@@H:2]([CH2:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:20]=[C:19]([O:21][C@H:22]([C:27]3[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][C:28]=3[N:34]3[CH:38]=[CH:37][C:36]([CH3:39])=[N:35]3)[C:23]([F:25])([F:26])[F:24])[N:18]=[C:17]([NH2:40])[N:16]=2)=[CH:13][CH:14]=1)[C:3]([O:5][CH2:6][CH3:7])=[O:4]

Komponenten

4

Edukt 2

HCID 464Hippuric AcidHCID 25181577Telotristat Ethyl

Produkt 1

HCID 25253377Telotristat EtiprateAusbeute 69 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 702EthanolLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

The 2×IPAc solution of (S)-Ethyl 2-amino-3-(4-(2-amino-6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)phenyl)propanoate was added to a thin slurry of hippuric acid (6.49 g, 36 mol, 1.0 equiv.) in IPAc (208 mL, 10×) and EtOH (42 mL, 2×) at 60° C. The clear yellow solution was then cooled to 50° C., at which time seeding was added and stirred for 1 h at the same temperature. The suspension was then slowly cooled to room temperature and stirred for 14 h at room temperature. The solids were filtered, washed with ice-cold IPAc (0-5° C., 42 mL, 2×) and dried under vacuum at 50° C. overnight to afford a white solid (19.0 g, 69% yield). M.p.: 145° C. (DSC onset temperature)

Aufarbeitung

  1. additionwas added
  2. temperatureThe suspension was then slowly cooled to room temperature
  3. stirringstirred for 14 h at room temperature
  4. filtrationThe solids were filtered
  5. washwashed with ice-cold IPAc (0-5° C., 42 mL, 2×)
  6. customdried under vacuum at 50° C. overnight

Quellen und Nachweise

ORD-Eintrag
ord-8c5d5c1157f647ce8eb58f78d8e6ef0f
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08193204B2

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