1-((2R,3R)-1-(benzyloxy)-4,4,4-trifluoro-3-hydroxybutan-2-yl)-3-((R)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)urea → 1-((R)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)-3-((2R,3R)-4,4,4-trifluoro-1,3-dihydroxybutan-2-yl)urea

HRID 1712711Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1712711
C([O:8][CH2:9][C@@H:10]([NH:17][C:18]([NH:20][C@@:21]([C:36]1[CH:41]=[C:40]([O:42][C:43]([F:48])([F:47])[CH:44]([F:46])[F:45])[CH:39]=[C:38]([F:49])[CH:37]=1)([C:29]1[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=1)[CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:19])[C@@H:11]([OH:16])[C:12]([F:15])([F:14])[F:13])C1C=CC=CC=1>C1COCC1.[OH-].[OH-].[Pd+2]>[F:49][C:38]1[CH:37]=[C:36]([C@:21]([NH:20][C:18]([NH:17][C@@H:10]([C@@H:11]([OH:16])[C:12]([F:13])([F:14])[F:15])[CH2:9][OH:8])=[O:19])([C:29]2[CH:30]=[CH:31][C:32]([F:35])=[CH:33][CH:34]=2)[CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:41]=[C:40]([O:42][C:43]([F:48])([F:47])[CH:44]([F:46])[F:45])[CH:39]=1

Komponenten

4

Edukt 1

HCID 594585491-((2R,3R)-1-(benzyloxy)-4,4,4-trifluoro-3-hydroxybutan-2-yl)-3-((R)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)urea

Produkt 1

HCID 235824681-((R)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)-3-((2R,3R)-4,4,4-trifluoro-1,3-dihydroxybutan-2-yl)urea

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9942167Palladium hydroxideKatalysatorHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of 1-((2R,3R)-1-(benzyloxy)-4,4,4-trifluoro-3-hydroxybutan-2-yl)-3-((R)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)urea (Example 236, 17 mg, 0.024 mmol) in THF (1 mL) was added 20% Pd(OH)2/C (8 mg) and the slurry was subjected to balloon hydrogenation for 18 h. The reaction mixture was filtered and the filtrate was concentrated and purified by preparative HPLC (Shimadzu-YMC-ODS-A 5μ column, 30×100 mm eluting with 30-100% MeOH (90% in H2O, 0.1% TFA) gradient over 12 min with flow rate 40 mL/min and UV detection at 220 nm) to yield 1-((R)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)-3-((2R,3R)-4,4,4-trifluoro-1,3-dihydroxybutan-2-yl)urea (Example 237) eluting at a retention time of 11.54 min as a clear oil (11 mg, yield 78%). LCMS: RT=1.983 min [M+H] 611.26 (Phenomenex Luna C18 column, 4.6×30 mm eluting with 10-90% MeOH/H2O over 2 minutes containing 0.1% TFA, 5 mL/min, monitoring at 220 nm); HPLC: RT=4.081 min, Purity 100% (Phenomenex Luna C18 column, 4.6×50 mm eluting with 10-90% MeOH/H2O over 4 minutes containing 0.2% PPA; 4 mL/min, monitoring at 220 nm); NMR: 400 MHz 1H (CDCl3) 7.20 ppm, 1H, s; 7.16 ppm, 5H, m; 6.99 ppm, 2H, m; 6.91 ppm, 3H, m; 6.70 ppm, 2H, d, J=7.47 Hz; 5.87 ppm, 1H, m; 5.38 ppm, 1H, d, J=7.47 Hz; 5.35 ppm, 1H, s; 4.28 ppm, 1H, d, J=5.71 Hz; 4.11 ppm, 2H, m; 3.94 ppm, 2H, d, J=7.91 Hz; 3.82 ppm, 1H, m; 3.73 ppm, 1H, m; 3.67 ppm, 1H, d, J=8.35 Hz.

Aufarbeitung

  1. customfor 18 h
  2. filtrationThe reaction mixture was filtered
  3. concentrationthe filtrate was concentrated
  4. custompurified by preparative HPLC (Shimadzu-YMC-ODS-A 5μ column, 30×100 mm eluting with 30-100% MeOH (90% in H2O, 0.1% TFA) gradient over 12 min with flow rate 40 mL/min and UV detection at 220 nm)

Quellen und Nachweise

ORD-Eintrag
ord-061e551675264b1eb8069db6695e9ee0
Quelldatensatz
uspto-grants-2010_09
Patentnummer
US07790770B2

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