Lithium Hydroxide → 1-Methoxy-2-propanol

HRID 74933

Reaktionsgleichung

Reaktionsgleichung von HRID 74933
[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH:17][C@H:18]4[CH2:23][CH2:22][CH2:21][C@@H:20]([NH2:24])[CH2:19]4)[C:14]([F:25])=[CH:13][N:12]=3)=[CH:9][N:8](S(C3C=CC(C)=CC=3)(=O)=O)[C:5]2=[N:6][CH:7]=1.ClC1C=C2C(C3N=C(N[C@@H]4CCC[C@H](N)C4)C(F)=CN=3)=CN(S(C3C=CC(C)=CC=3)(=O)=O)C2=NC=1.[CH3:71][O:72][CH2:73][CH:74]1[CH2:76][O:75]1.[Li+].[OH-]>CO>[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH:17][C@H:18]4[CH2:23][CH2:22][CH2:21][C@@H:20]([NH:24][CH2:76][CH:74]([OH:75])[CH2:73][O:72][CH3:71])[CH2:19]4)[C:14]([F:25])=[CH:13][N:12]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[CH3:71][O:72][CH2:73][CH:74]([OH:75])[CH3:76]

Komponenten

7

Edukt 4

HCID 3939Lithium HydroxideHCID 135891,2-Epoxy-3-methoxypropaneHCID 68008184(1R,3S)-N1-[2-[5-chloro-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridin-3-yl]-5-fluoro-pyrimidin-4-yl]cyclohexane-1,3-diamineHCID 68008346(1S,3R)-N1-[2-[5-chloro-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridin-3-yl]-5-fluoro-pyrimidin-4-yl]cyclohexane-1,3-diamine

Produkt 2

HCID 79001-Methoxy-2-propanolHCID 680077901-[[(1R,3S)-3-[[2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoro-pyrimidin-4-yl]amino]cyclohexyl]amino]-3-methoxy-propan-2-ol

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Reaktionsbedingungen

Temperatur
140 °C

Versuchsvorschrift

To a solution of (1S,3R)—N1-[2-[5-chloro-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridin-3-yl]-5-fluoro-pyrimidin-4-yl]cyclohexane-1,3-diamine, 20c, (50 mg, 0.09 mmol) in methanol (2 mL) was added 2-(methoxymethyl)oxirane (9.4 mg, 0.11 mmol) and the reaction mixture was heated in the microwave to 140° C. for 10 min. 1M aqueous LiOH (1.0 mL, 1.0 mmol) was added, and the reaction mixture was heated in the microwave to 130° C. for 10 min. The solvent was evaporated under reduced pressure, and the residue was purified by HPLC, using 5-70% CH3CN//H2O with 0.1% TFA over 15 minutes. The purified fractions were concentrated, redissolved in MeOH and passed through a carbonate-PS column to provide the free base of the desired product 1-[[(1R,3S)-3-[[2-(5-chloro-1H-pyrrolo[2, 3-1)]pyridin-3-yl)-5-fluoro-pyrimidin-4-yl]amino]cyclohexyl]amino]-3-methoxy-propan-2-ol, 610.

Aufarbeitung

  1. temperaturethe reaction mixture was heated in the microwave to 130° C. for 10 min
  2. customThe solvent was evaporated under reduced pressure
  3. customthe residue was purified by HPLC
  4. customover 15 minutes
  5. concentrationThe purified fractions were concentrated
  6. dissolutionredissolved in MeOH

Quellen und Nachweise

ORD-Eintrag
ord-8efa148eeba2439fb7ca0394deda3d1c
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08829007B2

Verknüpfte Notizen

Wird geladen…