Formaldehyde → (2S)-2-(methyl(4-(5-(2'-methyl-2-(trifluoromethyl)biphenyl-4-yl)-1,2,4-oxadiazol-3-yl)benzyl)amino)butanoic acid

HRID 572594Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 572594
[C:1]([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][C@@H:36]([CH2:40][CH3:41])[C:37]([OH:39])=[O:38].C=O>CO.CC(O)=O.C(Cl)Cl>[CH3:1][N:35]([CH2:27][C:26]1[CH:29]=[CH:30][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:34])[F:33])[CH:14]=3)[O:22][N:21]=2)=[CH:24][CH:25]=1)[C@@H:36]([CH2:40][CH3:41])[C:37]([OH:39])=[O:38]

Komponenten

8

Edukt 4

HCID 712FormaldehydeHCID 80283(-)-2-Aminobutyric acidHCID 5003444Sodium cyanoborohydride2×HCID 866615184-(5-(2'-Methyl-2-(trifluoromethyl)biphenyl-4-yl)-1,2,4-oxadiazol-3-yl)benzaldehyde

Produkt 1

HCID 56601974(2S)-2-(methyl(4-(5-(2'-methyl-2-(trifluoromethyl)biphenyl-4-yl)-1,2,4-oxadiazol-3-yl)benzyl)amino)butanoic 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 (Example 54, step 2, 103 mg; 0.25 mmol) and (S)-2-aminobutanoic acid (52 mg; 0.50 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 formaldehyde (37% aqueous solution; 204 mg, 2.51 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 8.57-8.53 (1H, m), 8.52-8.48 (1H, m), 8.10 (2H, d, J=8.0 Hz), 7.67 (1H, d, J=7.9 Hz), 7.57 (2H, d, J=8.0 Hz), 7.40-7.35 (2H, m), 7.32-7.27 (1H, m), 7.18 (1H, d, J=7.5 Hz), 3.86 (1H, d, J=14.3 Hz), 3.72 (1H, d, J=14.3 Hz), 3.15 (1H, t, J=7.4 Hz), 2.24 (3H, s), 2.03 (3H, s), 1.76-1.60 (2H, m), 0.95 (3H, t, J=7.3 Hz). LC/MS (Method B): 510 (M+H)+. HPLC (Method D) Rt 3.39 min (Purity: 99.8%).

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-e84b79b20c1b46fab908b0d15052e15c
Quelldatensatz
uspto-grants-2015_05
Patentnummer
US09029405B2

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