Acetone → (Isopropyl-{4-[5-(2'-methyl-2-trifluoromethyl-biphenyl-4-yl)-[1,2,4]oxadiazol-3-yl]-benzyl}-amino)-acetic acid

HRID 2404363Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2404363
C([BH3-])#N.[Na+].[CH3:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[C:12]1[CH:17]=[CH:16][C:15]([C:18]2[O:22][N:21]=[C:20]([C:23]3[CH:30]=[CH:29][C:26]([CH:27]=O)=[CH:25][CH:24]=3)[N:19]=2)=[CH:14][C:13]=1[C:31]([F:34])([F:33])[F:32].[NH2:35][CH2:36][C:37]([OH:39])=[O:38].[CH3:40][C:41]([CH3:43])=O>CO.CC(O)=O.C(Cl)Cl>[CH:41]([N:35]([CH2:36][C:37]([OH:39])=[O:38])[CH2:27][C:26]1[CH:25]=[CH:24][C:23]([C:20]2[N:19]=[C:18]([C:15]3[CH:16]=[CH:17][C:12]([C:7]4[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=4[CH3:5])=[C:13]([C:31]([F:32])([F:33])[F:34])[CH:14]=3)[O:22][N:21]=2)=[CH:30][CH:29]=1)([CH3:43])[CH3:40]

Komponenten

8

Edukt 4

HCID 180AcetoneHCID 750GlycineHCID 5003444Sodium cyanoborohydride2×HCID 866615184-(5-(2'-Methyl-2-(trifluoromethyl)biphenyl-4-yl)-1,2,4-oxadiazol-3-yl)benzaldehyde

Produkt 1

HCID 46931458(Isopropyl-{4-[5-(2'-methyl-2-trifluoromethyl-biphenyl-4-yl)-[1,2,4]oxadiazol-3-yl]-benzyl}-amino)-acetic acid

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 176Acetic AcidLösungsmittel2×HCID 887MethanolLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

Sodium cyanoborohydride (18 mg, 0.28 mmol) was added to a solution of 4-(5-(2′-methyl-2-(trifluoromethyl)biphenyl-4-yl)-1,2,4-oxadiazol-3-yl)benzaldehyde (0.25 mmol) and 2-aminoacetic acid (23 mg, 0.25 mmol) in a mixture of methanol (3 mL), DCM (3 mL) and acetic acid (38 μl). The mixture was stirred at room temperature overnight and was filtered through a frit under positive pressure. To the filtrate was added acetone (67 mg; 1.5 mmol) followed by addition of AcOH until the pH was in the range of 3-4 (240 mL). To the resulting mixture was added sodium cyanoborohydride (79 mg, 1.26 mmol), the mixture stirred for 16 hours, the solvent removed in vacuo and the residue purified by reverse phase HPLC to give a white solid as the title compound. 1H NMR (DMSO-d6, 400 MHz) δ 8.55-8.53 (1H, m), 8.53-8.48 (1H, m), 8.13-8.09 (2H, m), 7.71 (1H, d, J=7.9 Hz), 7.63 (2H, d, J=8.0 Hz), 7.37-7.34 (2H, m), 7.28-7.24 (1H, m), 7.15 (1H, d, J=7.5 Hz), 4.02 (2H, s), 3.24-3.22 (3H, m), 2.01 (3H, s), 1.11 (6H, d, J=6.5 Hz). LC/MS (Method A): 510 (M+H)+. HPLC (Method F) Rt=3.39 min (Purity: 99.1%).

Aufarbeitung

  1. filtrationwas filtered through a frit under positive pressure
  2. stirringthe mixture stirred for 16 hours
  3. customthe solvent removed in vacuo
  4. customthe residue purified by reverse phase HPLC

Quellen und Nachweise

ORD-Eintrag
ord-181ee85849d041e6a8af0b349e8aac0f
Quelldatensatz
uspto-grants-2014_08
Patentnummer
US08802704B2

Notizen zur Reaktion

Wird geladen…