2-Aminothiazole → 2,2-dimethyl-3-phenyl-3-(3-phenyl-1H-indazol-6-yl)-N-(thiazol-2-yl)propanamide

HRID 563395Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 563395
[CH3:1][C:2]([CH3:28])([CH:6]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:7]1[CH:15]=[C:14]2[C:10]([C:11]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[N:12][NH:13]2)=[CH:9][CH:8]=1)[C:3]([OH:5])=O.[NH2:29][C:30]1[S:31][CH:32]=[CH:33][N:34]=1.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH3:1][C:2]([CH3:28])([CH:6]([C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)[C:7]1[CH:15]=[C:14]2[C:10]([C:11]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[N:12][NH:13]2)=[CH:9][CH:8]=1)[C:3]([NH:29][C:30]1[S:31][CH:32]=[CH:33][N:34]=1)=[O:5]

Komponenten

6

Edukt 4

HCID 21552-AminothiazoleHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 670056622,2-dimethyl-3-phenyl-3-(3-phenyl-1H-indazol-6-yl)propanoic acid

Produkt 1

HCID 592527712,2-dimethyl-3-phenyl-3-(3-phenyl-1H-indazol-6-yl)-N-(thiazol-2-yl)propanamideAusbeute 28,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a stirred solution of 2,2-dimethyl-3-phenyl-3-(3-phenyl-1H-indazol-6-yl)propanoic acid (26 mg, 0.07 mmol), 2-aminothiazole (28 mg, 0.28 mmol), and diisopropylethylamine (0.05 mL) in anhydrous DMF (0.2 mL) was added HATU (106 mg, 0.28 mmol) under argon. After stirring at rt for 2.5 hr and 80° C. for 1 hr, the mixture was concentrated. Purification using reverse phase HPLC (YMC S5 20×100 mm, 10 min. run, solvent A: 10% MeOH: 90% H2O: 0.1% TFA, solvent B: 90% MeOH, 10% H2O, 0.1% TFA) gave 2,2-dimethyl-3-phenyl-3-(3-phenyl-1H-indazol-6-yl)-N-(thiazol-2-yl)propanamide (Example 112, 9 mg, 0.02 mmol, 28% yield) as a solid. MS found: (M+H)+=453. 1H-NMR (500 MHz, CDCl3) δ ppm 7.96 (1H, d, J=8.25 Hz) 7.86 (2H, d, J=8.25 Hz) 7.50 (1H, d, J=8.25 Hz) 7.46 (2H, d, J=8.25 Hz) 7.39-7.43 (2H, m) 7.35 (2H, d, J=7.70 Hz) 7.17-7.26 (4 H, m), 6.96 (1H, d, J=3.30 Hz) 4.62 (1H, s) 1.45 (6H, d, J=3.85 Hz).

Aufarbeitung

  1. concentrationthe mixture was concentrated
  2. customPurification
  3. customphase HPLC (YMC S5 20×100 mm, 10 min. run, solvent A: 10% MeOH: 90% H2O: 0.1% TFA, solvent B: 90% MeOH, 10% H2O, 0.1% TFA)

Quellen und Nachweise

ORD-Eintrag
ord-f159853ab02b41e2b8f7a9eface7f24b
Quelldatensatz
uspto-grants-2011_11
Patentnummer
US08067447B2

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