4-Methylmorpholine → 2-hydroxy-N-(oxazol-5-ylmethyl)-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide

HRID 77133

Reaktionsgleichung

Reaktionsgleichung von HRID 77133
[OH:1][CH:2]([C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:16]=[C:15]([C:17]3[O:21][N:20]=[C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[C:18]=3[C:28]([F:31])([F:30])[F:29])[O:14][N:13]=2)=[CH:8][CH:7]=1)[C:3](O)=[O:4].C[N:33]1[CH2:38][CH2:37][O:36][CH2:35]C1.F[P-](F)(F)(F)(F)F.[N:46]1(O[P+](N(C)C)(N(C)C)N(C)C)[C:50]2C=CC=CC=2N=N1>CN(C=O)C>[OH:1][CH:2]([C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:16]=[C:15]([C:17]3[O:21][N:20]=[C:19]([C:22]4[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=4)[C:18]=3[C:28]([F:31])([F:30])[F:29])[O:14][N:13]=2)=[CH:8][CH:7]=1)[C:3]([NH:46][CH2:50][C:37]1[O:36][CH:35]=[N:33][CH:38]=1)=[O:4]

Komponenten

5

Edukt 3

HCID 79724-MethylmorpholineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 674589572-Hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetic acid

Produkt 1

HCID 534966012-hydroxy-N-(oxazol-5-ylmethyl)-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamideAusbeute 39,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

2-Hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetic acid (Int-Va, 35 mg, 0.081 mmol) was dissolved in DMF (1 mL) prior to the addition of 4-methylmorpholine (0.054 mL, 0.487 mmol), oxazol-5-ylmethanamine, HCl (19.65 mg, 0.146 mmol), and BOP (64.6 mg, 0.146 mmol). This was stirred overnight and was then purified by preparative HPLC (PHENOMENEX® Luna 5u C18 21.2×100 mm, gradient elution with Method 1—MeOH/water containing 0.1% trifluoroacetic acid as defined above, 0% B to 100% B over 10 min, 20 mL/min, 220 nM, product retention time=11.6 min) to give single enantiomer 2-hydroxy-N-(oxazol-5-ylmethyl)-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide (17.2 mg, 0.032 mmol, 38.8% yield): LCMS=512.3 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.13-8.25 (2 H, m), 7.66-7.78 (4 H, m), 7.54-7.66 (4 H, m), 6.04 (1 H, s), 5.19 (1 H, s), 4.51 (2 H, s). HPLC Peak RT=10.1 min (Analytical Method D).

Aufarbeitung

  1. customwas then purified by preparative HPLC (PHENOMENEX® Luna 5u
  2. washC18 21.2×100 mm, gradient elution with Method 1—MeOH/water containing 0.1% trifluoroacetic acid
  3. customover 10 min

Quellen und Nachweise

ORD-Eintrag
ord-c482eb9c87254f04b0a91eaf936c693f
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08835470B2

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