2-Amino-4-methylthiazole → 3-{[5-(azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-N-(4-methyl-1,3-thiazol-2-yl)-5-[(3S)-tetrahydrofuran-3-yloxy]benzamide

HRID 1990001Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1990001
[N:1]1([C:5]([C:7]2[N:8]=[CH:9][C:10]([O:13][C:14]3[CH:15]=[C:16]([CH:20]=[C:21]([O:23][C@H:24]4[CH2:28][CH2:27][O:26][CH2:25]4)[CH:22]=3)[C:17]([OH:19])=O)=[N:11][CH:12]=2)=[O:6])[CH2:4][CH2:3][CH2:2]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:53][C:54]1[S:55][CH:56]=[C:57]([CH3:59])[N:58]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[N:1]1([C:5]([C:7]2[N:8]=[CH:9][C:10]([O:13][C:14]3[CH:15]=[C:16]([CH:20]=[C:21]([O:23][C@H:24]4[CH2:28][CH2:27][O:26][CH2:25]4)[CH:22]=3)[C:17]([NH:53][C:54]3[S:55][CH:56]=[C:57]([CH3:59])[N:58]=3)=[O:19])=[N:11][CH:12]=2)=[O:6])[CH2:4][CH2:3][CH2:2]1

Komponenten

6

Edukt 4

HCID 741432-Amino-4-methylthiazoleHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 591271123-{[5-(Azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-5-[(3S)-tetrahydrofuran-3-yloxy]benzoic acid

Produkt 1

HCID 160399703-{[5-(azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-N-(4-methyl-1,3-thiazol-2-yl)-5-[(3S)-tetrahydrofuran-3-yloxy]benzamideAusbeute 28 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

3-{[5-(Azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-5-[(3S)-tetrahydrofuran-3-yloxy]benzoic acid (200 mg, 0.52 mmol), HATU (475 mg, 1.25 mmol) and 2-amino-4-methylthiazole (119 mg, 1.04 mmol) were suspended in DMF (2 mL). DIPEA (0.220 mL, 1.26 mmol) was then added and the reaction mixture stirred at RT for 16 hours. The DMF was removed in vacuo and water (15 mL) added. The mixture was extracted with ethyl acetate (3×20 mL) and the extracts combined, washed with water (15 mL), 1N hydrochloric acid (10 mL), water (10 mL), a saturated aqueous solution of sodium bicarbonate (10 mL), brine (10 mL), dried (MgSO4), filtered, and evaporated in vacuo. The residue was chromatographed on silica, eluting with a gradient of 60-100% ethyl acetate in isohexane, to give the desired compound (70 mg).

Aufarbeitung

  1. customThe DMF was removed in vacuo and water (15 mL)
  2. additionadded
  3. extractionThe mixture was extracted with ethyl acetate (3×20 mL)
  4. washwashed with water (15 mL), 1N hydrochloric acid (10 mL), water (10 mL)
  5. dry with materiala saturated aqueous solution of sodium bicarbonate (10 mL), brine (10 mL), dried (MgSO4)
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe residue was chromatographed on silica
  9. washeluting with a gradient of 60-100% ethyl acetate in isohexane

Quellen und Nachweise

ORD-Eintrag
ord-1f059f51d387420b935ca69171c10f29
Quelldatensatz
uspto-grants-2010_01
Patentnummer
US07642263B2

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