Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → (R)-ethyl 4-(5'-fluoro-2'-methoxybiphenyl-4-yl)-3-(oxazole-5-carboxamido)butanoate

HRID 881816Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 881816
[O:1]1[C:5]([C:6]([OH:8])=O)=[CH:4][N:3]=[CH:2]1.Cl.[NH2:10][C@H:11]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:26]=2[O:32][CH3:33])=[CH:21][CH:20]=1)[CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.C(Cl)Cl>[F:31][C:29]1[CH:28]=[CH:27][C:26]([O:32][CH3:33])=[C:25]([C:22]2[CH:21]=[CH:20][C:19]([CH2:18][C@@H:11]([NH:10][C:6]([C:5]3[O:1][CH:2]=[N:3][CH:4]=3)=[O:8])[CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:24][CH:23]=2)[CH:30]=1

Komponenten

6

Edukt 3

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 163405571,3-Oxazole-5-carboxylic acidHCID 68423640(R)-ethyl 3-amino-4-(5'-fluoro-2'-methoxybiphenyl-4-yl)butanoate hydrochloride

Produkt 1

HCID 59607772(R)-ethyl 4-(5'-fluoro-2'-methoxybiphenyl-4-yl)-3-(oxazole-5-carboxamido)butanoate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of oxazole-5-carboxylic acid (70 mg, 0.61 mmol) in DMF (1.5 mL) and DCM (1.5 mL) is added (R)-ethyl 3-amino-4-(5′-fluoro-2′-methoxybiphenyl-4-yl)butanoate hydrochloride, intermediate 8-3, (150 mg, 0.41 mmol), HATU (233 mg, 0.61 mmol), and TEA (284 μL, 2.04 mmol). After stirring for 2 hours, the reaction is quenched with H2O, and the crude is diluted with EtOAc, the organic layer is washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The obtained residue is purified by RP-HPLC (SunFire C18, H2O (0.1% TFA)/CH3CN), and then lyophilized to give (R)-ethyl 4-(5′-fluoro-2′-methoxybiphenyl-4-yl)-3-(oxazole-5-carboxamido)butanoate (157 mg). HPLC retention time=1.50 minutes (condition A); MS (m+1)=427.4; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.19 (t, J=7.2 Hz, 3 H) 2.46-2.62 (m, 2 H) 2.86 (dd, J=13.6, 8.1 Hz, 1 H) 3.02 (dd, J=13.6, 6.1 Hz, 1 H) 3.67 (s, 3 H) 4.05-4.15 (m, 2 H) 4.52-4.69 (m, 1 H) 6.76-6.82 (m, 1 H) 6.83-6.96 (m, 2 H) 7.11-7.21 (m, 3 H) 7.37 (d, J=8.1 Hz, 2 H) 7.61 (s, 1 H) 7.80 (s, 1 H)

Aufarbeitung

  1. customthe reaction is quenched with H2O
  2. additionthe crude is diluted with EtOAc
  3. washthe organic layer is washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe obtained residue is purified by RP-HPLC (SunFire C18, H2O (0.1% TFA)/CH3CN)

Quellen und Nachweise

ORD-Eintrag
ord-94941ad6da1d46189ce3e351aecbe8f7
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08993631B2

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