Triethylamine → 2-Cyclohexyl-2-[5-fluoro-2-((R)-methoxy-phenyl-methyl)-benzoimidazol-1-yl]-N-(4-hydroxy-cyclohexyl)-acetamide

HRID 1170701Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1170701
[CH:1]1([CH:7]([N:11]2[C:15]3[CH:16]=[CH:17][C:18]([F:20])=[CH:19][C:14]=3[N:13]=[C:12]2[C@H:21]([O:28][CH3:29])[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:8](O)=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[NH2:62][C@H:63]1[CH2:68][CH2:67][C@H:66]([OH:69])[CH2:65][CH2:64]1>CN(C=O)C>[CH:1]1([CH:7]([N:11]2[C:15]3[CH:16]=[CH:17][C:18]([F:20])=[CH:19][C:14]=3[N:13]=[C:12]2[C@H:21]([O:28][CH3:29])[C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[C:8]([NH:62][CH:63]2[CH2:68][CH2:67][CH:66]([OH:69])[CH2:65][CH2:64]2)=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Komponenten

6

Edukt 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66810397Cyclohexyl-[5-fluoro-2-((R)-methoxy-phenyl-methyl)-benzoimidazol-1-yl]-acetic acidHCID 178479278HCID 178479278, Verbindung

Produkt 1

HCID 673723982-Cyclohexyl-2-[5-fluoro-2-((R)-methoxy-phenyl-methyl)-benzoimidazol-1-yl]-N-(4-hydroxy-cyclohexyl)-acetamideAusbeute 40,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

To a solution of cyclohexyl-[5-fluoro-2-((R)-methoxy-phenyl-methyl)-benzoimidazol-1-yl]-acetic acid (100 mg, 0.25 mmol, 1.0 equiv) in DMF (1.5 mL) was added triethylamine (51.1 mg, 70.0 μL, 0.50 mmol, 2.0 equiv) and HATU (124.7 mg, 0.33 mmol, 1.3 equiv) and the mixture stirred at 40° C. After 15 min, trans-4-amino-cyclohexanol hydrochloride (50.03 mg, 0.33 mmol, 1.3 equiv; [CAS RN 50910-54-8]) was added and stirring continued at 50° C. for 2 h. Removal of the solvent mixture under reduced pressure and purification by preparative HPLC on reversed phase eluting with a gradient of acetonitrile/water provided 50 mg (40%) of the title compound.

Aufarbeitung

  1. stirringstirring
  2. waitcontinued at 50° C. for 2 h
  3. customRemoval of the solvent mixture
  4. customunder reduced pressure and purification by preparative HPLC on reversed phase
  5. washeluting with a gradient of acetonitrile/water

Quellen und Nachweise

ORD-Eintrag
ord-682ee0d282644ab18f7503c4bc33afd4
Quelldatensatz
uspto-grants-2010_11
Patentnummer
US07825258B2

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