Hydrochloric Acid → 1-[4-((2R,4S)-4-{(3,5-bis-trifluoromethyl-benzyl)-[5-(1H-pyrazol-4-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidin-1-yl)-5-chloro-pyrimidin-2-yl]-piperidine-4-carboxylic acid

HRID 409451Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 409451
C([O:3][C:4]([CH:6]1[CH2:11][CH2:10][N:9]([C:12]2[N:17]=[C:16]([N:18]3[CH2:22][C@@H:21]([N:23]([CH2:35][C:36]4[CH:41]=[C:40]([C:42]([F:45])([F:44])[F:43])[CH:39]=[C:38]([C:46]([F:49])([F:48])[F:47])[CH:37]=4)[C:24]4[N:29]=[CH:28][C:27]([C:30]5[CH:31]=[N:32][NH:33][CH:34]=5)=[CH:26][N:25]=4)[CH2:20][C@H:19]3[CH2:50][CH3:51])[C:15]([Cl:52])=[CH:14][N:13]=2)[CH2:8][CH2:7]1)=[O:5])C.[Li+].[OH-].Cl>CO>[F:49][C:46]([F:47])([F:48])[C:38]1[CH:37]=[C:36]([CH:41]=[C:40]([C:42]([F:43])([F:44])[F:45])[CH:39]=1)[CH2:35][N:23]([C:24]1[N:25]=[CH:26][C:27]([C:30]2[CH:34]=[N:33][NH:32][CH:31]=2)=[CH:28][N:29]=1)[C@@H:21]1[CH2:22][N:18]([C:16]2[C:15]([Cl:52])=[CH:14][N:13]=[C:12]([N:9]3[CH2:8][CH2:7][CH:6]([C:4]([OH:5])=[O:3])[CH2:11][CH2:10]3)[N:17]=2)[C@H:19]([CH2:50][CH3:51])[CH2:20]1

Komponenten

5

Edukt 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 866483941-[4-((2R,4S)-4-{(3,5-bis-trifluoromethyl-benzyl)-[5-(1H-pyrazol-4-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidin-1-yl)-5-chloro-pyrimidin-2-yl]-piperidine-4-carboxylic acid ethyl ester

Produkt 1

HCID 596144111-[4-((2R,4S)-4-{(3,5-bis-trifluoromethyl-benzyl)-[5-(1H-pyrazol-4-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidin-1-yl)-5-chloro-pyrimidin-2-yl]-piperidine-4-carboxylic acidAusbeute 20 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Versuchsvorschrift

A 15 ml round-bottom flask is charged with 1-[4-((2R,4S)-4-{(3,5-bis-trifluoromethyl-benzyl)-[5-(1H-pyrazol-4-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidin-1-yl)-5-chloro-pyrimidin-2-yl]-piperidine-4-carboxylic acid ethyl ester, 2N LiOH (0.4 ml, 0.8 mmol) THF (0.5 ml) and MeOH (1 ml). The mixture is then stirred at rt for 1 hour. PH is adjusted to 6 using 1 N HCl and resulted solution is extracted with EtOAc. The organic layer is dried over Na2SO4 and removal of solvent, purification with reverse phase column give 1-[4-((2R,4S)-4-{(3,5-bis-trifluoromethyl-benzyl)-[5-(1H-pyrazol-4-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidin-1-yl)-5-chloro-pyrimidin-2-yl]-piperidine-4-carboxylic acid (13 mg, 0.017 mmol, 20% for 3 steps).

Aufarbeitung

  1. customresulted solution
  2. extractionis extracted with EtOAc
  3. dry with materialThe organic layer is dried over Na2SO4 and removal of solvent, purification with reverse phase column

Quellen und Nachweise

ORD-Eintrag
ord-443e7d23d1ce43e1976866b181876d0d
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08759365B2

Notizen zur Reaktion

Wird geladen…