Potassium Carbonate → 3-(4-(Difluoromethoxy)-2-methylphenyl)-7-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2,6-dimethylpyrazolo[5,1-b]oxazole

HRID 1696862Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1696862
[CH3:1][C:2]1[N:6]=[C:5]([CH3:7])[N:4]([C:8]2[C:9]([CH3:25])=[N:10][N:11]3[C:15]([C:16]4[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][C:17]=4[CH3:23])=[C:14]([CH3:24])[O:13][C:12]=23)[N:3]=1.C(=O)([O-])[O-].[K+].[K+].Cl[C:33]([F:39])([F:38])C(OC)=O>CN(C=O)C>[F:38][CH:33]([F:39])[O:22][C:19]1[CH:20]=[CH:21][C:16]([C:15]2[N:11]3[N:10]=[C:9]([CH3:25])[C:8]([N:4]4[C:5]([CH3:7])=[N:6][C:2]([CH3:1])=[N:3]4)=[C:12]3[O:13][C:14]=2[CH3:24])=[C:17]([CH3:23])[CH:18]=1

Komponenten

5

Edukt 3

HCID 11430Potassium CarbonateHCID 73935Methyl chlorodifluoroacetateHCID 672125924-(7-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2,6-dimethylpyrazolo[5,1-b]oxazol-3-yl)-3-methylphenol

Produkt 1

HCID 533087423-(4-(Difluoromethoxy)-2-methylphenyl)-7-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2,6-dimethylpyrazolo[5,1-b]oxazole

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

A solution of 4-(7-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2,6-dimethylpyrazolo[5,1-b]oxazol-3-yl)-3-methylphenol (Step 1) (100 mg, 0.296 mmol) in dry DMF (4 ml) was treated with potassium carbonate (205 mg, 1.482 mmol) and stirred under N2 for 30 mins at 50° C. Methyl 2-chloro-2,2-difluoroacetate (428 mg, 2.96 mmol) was added and the reaction was heated to 90° C. for 1.5 hrs. After cooling to RT, the mixture was partitioned between EtOAc and water. The organic portion was washed with brine, dried (MgSO4) and concentrated in vacuo to give a brown oil. Purification of the crude product by reverse phase chromatography [prep-HPLC (Waters system)] yielded the title compound (TFA salt) as a colourless oil. The salt was taken up in DCM (2 ml) and MP-carbonate resin (macroporous polystyrene anion-exchange resin) (500 mg, 2.8 mmol/g, Argonaut) was added and the contents stirred at RT for 30 mins. The resin was filtered, washed with DCM and the filtrate was concentrated in vacuo to give the title compound as the free base. LC-MS Rt 4.86 mins; MS m/z 388.2 [M+H]+; Method=10minLC_v002. 1H NMR (400 MHz, CDCl3) δ 7.4 (1H, d), 7.15 (1H, s), 7.10 (1H, d), 6.6 (1H, t), 2.40 (6H, m), 2.35 (6H, m), 2.20 (3H, s).

Aufarbeitung

  1. temperaturethe reaction was heated to 90° C. for 1.5 hrs
  2. temperatureAfter cooling to RT
  3. customthe mixture was partitioned between EtOAc and water
  4. washThe organic portion was washed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customto give a brown oil
  8. customPurification of the crude product by reverse phase chromatography [prep-HPLC (Waters system)]

Quellen und Nachweise

ORD-Eintrag
ord-825c305503e945858531cf733e727e66
Quelldatensatz
uspto-grants-2012_04
Patentnummer
US08163785B2

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