Potassium Carbonate → 8-(1-cyclopropyl-6-fluoro-1H-benzimidazol-2-yl)-1,6-naphthyridine

HRID 1048947Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1048947
[CH:1]1([NH:4][C:5]2[C:6]([NH2:12])=[CH:7][CH:8]=[C:9]([F:11])[CH:10]=2)[CH2:3][CH2:2]1.[N:13]1[C:22]2[C:17](=[CH:18][N:19]=[CH:20][C:21]=2[CH:23]=O)[CH:16]=[CH:15][CH:14]=1.OOS([O-])=O.[K+].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O.C(OCC)(=O)C>[CH:1]1([N:4]2[C:5]3[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:6]=3[N:12]=[C:23]2[C:21]2[CH:20]=[N:19][CH:18]=[C:17]3[C:22]=2[N:13]=[CH:14][CH:15]=[CH:16]3)[CH2:3][CH2:2]1

Komponenten

8

Edukt 4

HCID 11430Potassium CarbonateHCID 23707502Potassium hydroxy sulfiteHCID 534219291,6-Naphthyridine-8-carbaldehydeHCID 545925541-N-cyclopropyl-5-fluorobenzene-1,2-diamine

Produkt 1

HCID 566453598-(1-cyclopropyl-6-fluoro-1H-benzimidazol-2-yl)-1,6-naphthyridine

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittel2×HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel2×

Versuchsvorschrift

To a solution of N2-cyclopropyl-4-fluorobenzene-1,2-diamine (0.080 g, 0.48 mmol) in DMF (1.17 mL) and water (0.04 mL) were added the title compound from Example 8 Step A (0.084 g, 0.53 mmol) and OXONE® (0.192 g, 0.313 mmol). The resulting mixture was stirred at room temperature for 1 hour, then diluted with ethyl acetate and water. Solid potassium carbonate was added until the aqueous layer was basic (pH ˜9). Ethyl acetate was added, and the organic layer was separated, washed with water and brine, dried over magnesium sulfate, filtered and concentrated. Purification by flash chromatography on silica gel (50% ethyl acetate in hexanes, then 100% ethyl acetate) provided the title compound: LCMS m/z 304.99 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 9.09 (s, 1 H), 9.13 (m, 1 H), 9.07 (s, 1 H), 8.43 (d, J=8.3 Hz, 1 H), 7.78 (dd, J=8.7, 4.8 Hz, 1 H), 7.63 (dd, J=8.2, 4.2 Hz, 1 H), 7.34 (dd, J=8.7, 2.2 Hz, 1 H), 7.07 (m, 1 H), 3.55-3.53 (m, 1 H), 0.62-0.61 (m, 4 H).

Aufarbeitung

  1. customthe organic layer was separated
  2. washwashed with water and brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by flash chromatography on silica gel (50% ethyl acetate in hexanes

Quellen und Nachweise

ORD-Eintrag
ord-eca0fbf5738847e48ee478121c018bbf
Quelldatensatz
uspto-grants-2016_07
Patentnummer
US09382226B2

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