Diisopropylethylamine → 4'-Fluoro-2'-methyl-biphenyl-3-carboxylic acid [4-(2-methylsulfanylpyrimidin-4-yloxy)-naphthalen-1-yl]-amide

HRID 1171419Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1171419
[CH3:1][S:2][C:3]1[N:8]=[C:7]([O:9][C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]([NH2:20])=[CH:12][CH:11]=2)[CH:6]=[CH:5][N:4]=1.[F:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[CH:29]=[C:30]([CH:34]=[CH:35][CH:36]=2)[C:31](O)=[O:32])=[C:24]([CH3:37])[CH:23]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C)C=O.C(OCC)(=O)C>[CH3:1][S:2][C:3]1[N:8]=[C:7]([O:9][C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]([NH:20][C:31]([C:30]3[CH:29]=[C:28]([C:25]4[CH:26]=[CH:27][C:22]([F:21])=[CH:23][C:24]=4[CH3:37])[CH:36]=[CH:35][CH:34]=3)=[O:32])=[CH:12][CH:11]=2)[CH:6]=[CH:5][N:4]=1

Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 549122783-(4-Fluoro-2-methylphenyl)benzoic acidHCID 595533854-(2-Methylsulfanylpyrimidin-4-yloxy)-naphthalen-1-ylamine

Produkt 1

HCID 595531874'-Fluoro-2'-methyl-biphenyl-3-carboxylic acid [4-(2-methylsulfanylpyrimidin-4-yloxy)-naphthalen-1-yl]-amideAusbeute 13,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

4-(2-Methylsulfanylpyrimidin-4-yloxy)-naphthalen-1-ylamine (320 mg, 1 mmol), 3-(4-fluoro-2-methylphenyl)benzoic acid (230 mg, 1.0 mmol), HBTU (569 mg, 1.5 mmol) and diisopropylethylamine (0.53 ml, 3.0 mmol) are stirred at room temperature in anhydrous dimethylformamide (5 ml) for 1 day. The mixture is then poured into ethyl acetate (100 ml) and washed with water (100 ml). The organic layer is then dried over anhydrous sodium sulfate and evaporated to dryness. The residue is purified by column chromatography on silica gel eluted with 20-30-40% ethyl acetate in hexanes to give product as a pink solid recrystallized from ethyl acetate/hexanes to give 4′-fluoro-2′-methyl-biphenyl-3-carboxylic acid [4-(2-methylsulfanylpyrimidin-4-yloxy)-naphthalen-1-yl]-amide as pink crystals (67 mg). 1H NMR 400 MHz (CDCl3) 8.30 (d, 1H, J=6 Hz), 8.14 (s, 1H), 8.0 (d, 1H, J=8 Hz), 7.86-7.92 (m, 4H), 7.44-7.56 (m, 4H), 7.28 (d, 1H, J=8.4), 7.18 (m, 1H), 6.9-6.97 (m, 2H), 6.46 (d, 1H, J=5.6 Hz), 2.23 (d, 6H).

Aufarbeitung

  1. washwashed with water (100 ml)
  2. dry with materialThe organic layer is then dried over anhydrous sodium sulfate
  3. customevaporated to dryness
  4. customThe residue is purified by column chromatography on silica gel
  5. washeluted with 20-30-40% ethyl acetate in hexanes
  6. customto give product as a pink solid
  7. customrecrystallized from ethyl acetate/hexanes

Quellen und Nachweise

ORD-Eintrag
ord-806a58d08833408cab90a008f7713fa9
Quelldatensatz
uspto-grants-2010_11
Patentnummer
US07829560B2

Notizen zur Reaktion

Wird geladen…