1-Methyl-1H-imidazol-2-amine → 2,2-Difluoro-N-[(1S,2R)-1-fluoromethyl-2-hydroxy-2-(4-{6-[(1-methyl-1H-imidazol-2-ylamino)-methyl]-pyridin-3-yl}-phenyl)-ethyl]-acetamide

HRID 1487570Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1487570
Cl[CH2:2][C:3]1[N:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([C@H:15]3[O:19]C(C)(C)[N:17]([C:22](=[O:26])[CH:23]([F:25])[F:24])[C@@H:16]3[CH2:27][F:28])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.[CH3:29][N:30]1[CH:34]=[CH:33][N:32]=[C:31]1[NH2:35]>CN(C)C=O>[F:25][CH:23]([F:24])[C:22]([NH:17][C@H:16]([CH2:27][F:28])[C@H:15]([OH:19])[C:12]1[CH:13]=[CH:14][C:9]([C:6]2[CH:7]=[N:8][C:3]([CH2:2][NH:35][C:31]3[N:30]([CH3:29])[CH:34]=[CH:33][N:32]=3)=[CH:4][CH:5]=2)=[CH:10][CH:11]=1)=[O:26]

Komponenten

4

Edukt 2

HCID 5663211-Methyl-1H-imidazol-2-amineHCID 866955331-{(4S,5R)-5-[4-(6-Chloromethyl-pyridin-3-yl)-phenyl]-4-fluoromethyl-2,2-dimethyl-oxazolidin-3-yl}-2,2-difluoro-ethanone

Produkt 1

HCID 897910372,2-Difluoro-N-[(1S,2R)-1-fluoromethyl-2-hydroxy-2-(4-{6-[(1-methyl-1H-imidazol-2-ylamino)-methyl]-pyridin-3-yl}-phenyl)-ethyl]-acetamideAusbeute 26,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A solution of 1-{(4S,5R)-5-[4-(6-chloromethyl-pyridin-3-yl)-phenyl]-4-fluoromethyl-2,2-dimethyl-oxazolidin-3-yl}-2,2-difluoro-ethanone (25 mg, 0.06 mmol) and 1-Methyl-1H-imidazol-2-ylamine (30 mg, 0.3 mmol) in dimethyl formamide (2 ml) is heated at 75° C. for 16 h. The reaction mixture is concentrated to dryness, dissolved in CH2Cl2 (1 ml) and treated with trifluoroacetic acid (0.5 ml) and water (0.1 ml). The mixture is shaken at ambient temperature for 2 hours and then concentrated to dryness. The crude product is purified by preparative HPLC to give the title compound (7 mg): 1H NMR (400 MHz, DMSO-d6) 2.50 (s, 3H), 3.51 (s, 2H), 4.24-4.36 (m, 1.5H), 4.37-4.46 (m, 0.5H), 4.51-4.59 (m, 0.5H), 4.63-4.71 (m, 0.5H), 4.87-4.92 (m, 1H), 5.31 (s, 2H), 6.22 (t, 1H), 7.05-7.10 (m, 2H), 7.40-7.52 (m, 3H), 7.66-7.74 (m, 2H), 8.09-8.16 (m, 1H), 8.86 (s, 1H), 9.63-9.69 (m, 1H). m/z M+H 434.

Aufarbeitung

  1. concentrationThe reaction mixture is concentrated to dryness
  2. dissolutiondissolved in CH2Cl2 (1 ml)
  3. additiontreated with trifluoroacetic acid (0.5 ml) and water (0.1 ml)
  4. concentrationconcentrated to dryness
  5. customThe crude product is purified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-3744e3aa37ad4de59201133d373877e2
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09428528B2

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