HCID 66678959, Verbindung → (S)-1-(3-fluoro-4-(4-(5-fluoro-2-(methylsulfonyl)phenyl)-6-(3-methylmorpholino)pyrimidin-2-yl)phenyl)-3-(2-hydroxyethyl)urea

HRID 1771579Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1771579
FC1C=C(C2N=C(SC)N=C(N3CCOC[C@@H]3C)C=2)C=NC=1.Cl[C:24]1[N:29]=[C:28]([N:30]2[CH2:35][CH2:34][O:33][CH2:32][C@@H:31]2[CH3:36])[CH:27]=[C:26]([C:37]2[CH:42]=[C:41]([F:43])[CH:40]=[CH:39][C:38]=2[S:44]([CH3:47])(=[O:46])=[O:45])[N:25]=1.[F:48][C:49]1[CH:50]=[C:51]([NH:64][C:65]([NH:67][CH2:68][CH2:69][OH:70])=[O:66])[CH:52]=[CH:53][C:54]=1B1OC(C)(C)C(C)(C)O1>CO.Cl>[F:48][C:49]1[CH:50]=[C:51]([NH:64][C:65]([NH:67][CH2:68][CH2:69][OH:70])=[O:66])[CH:52]=[CH:53][C:54]=1[C:24]1[N:25]=[C:26]([C:37]2[CH:42]=[C:41]([F:43])[CH:40]=[CH:39][C:38]=2[S:44]([CH3:47])(=[O:46])=[O:45])[CH:27]=[C:28]([N:30]2[CH2:35][CH2:34][O:33][CH2:32][C@@H:31]2[CH3:36])[N:29]=1

Komponenten

6

Edukt 3

HCID 66678959HCID 66678959, Verbindung2×HCID 67382782(S)-4-(6-(5-fluoropyridin-3-yl)-2-(methylthio)pyrimidin-4-yl)-3-methylmorpholineHCID 86691149(S)-4-(2-chloro-6-(5-fluoro-2-(methylsulfonyl)phenyl)pyrimidin-4-yl)-3-methylmorpholine2×

Produkt 1

HCID 53379951(S)-1-(3-fluoro-4-(4-(5-fluoro-2-(methylsulfonyl)phenyl)-6-(3-methylmorpholino)pyrimidin-2-yl)phenyl)-3-(2-hydroxyethyl)urea

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 313Hydrochloric AcidKatalysatorHCID 887MethanolLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

Method as described for intermediate 5 using (S)-4-(2-chloro-6-(5-fluoro-2-(methylsulfonyl)phenyl)pyrimidin-4-yl)-3-methylmorpholine (intermediate 10) and 1-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-3-(2-hydroxyethyl)urea (intermediate 13). Material was purified by prep HPLC (high pH) followed by purification by prep HPLC (low pH). Due to partial byproduct formation by reaction with formic acid the resulting material was taken up in MeOH (0.5 mL) along with 2 drops of 2M HCl and heated in the microwave for 20 minutes at 90° C. Reaction mixture was purified using a TsOH cartridge (100 mg) to afford a white solid, (12 mg, 8%).

Aufarbeitung

  1. customMaterial was purified by prep HPLC (high pH)
  2. customfollowed by purification by prep HPLC (low pH)
  3. customDue to partial byproduct formation by reaction with formic acid the resulting material
  4. customReaction mixture
  5. customwas purified
  6. customto afford a white solid, (12 mg, 8%)

Quellen und Nachweise

ORD-Eintrag
ord-2d2d594881564750b7fcaa7030c6252f
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09249129B2

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