2,3-Dichlorobenzaldehyde → 4,7-Dihydro-5-methyl-7-(1-methylethyl)pyrazolo[1,5-a]pyrimidine-6-carboxylic Acid 1,1-dimethylethyl Ester

HRID 49273

Reaktionsgleichung

Reaktionsgleichung von HRID 49273
Cl[C:2]1[C:9](Cl)=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].[C:11]([O:15]CC(=O)CC([O-])=O)([CH3:14])([CH3:13])[CH3:12].[NH2:23][C:24]1[CH:28]=[CH:27][NH:26][N:25]=1.[C:29]([O-])(=O)C.[Na+]>CN(C)C=O>[CH3:14][C:11]([O:15][C:4]([C:3]1[CH:2]([CH:9]([CH3:8])[CH3:29])[N:25]2[N:26]=[CH:27][CH:28]=[C:24]2[NH:23][C:6]=1[CH3:7])=[O:5])([CH3:12])[CH3:13]

Komponenten

6

Edukt 4

HCID 357452,3-DichlorobenzaldehydeHCID 517045Sodium AcetateHCID 17886005t-ButoxyacetoacetateHCID 178418806HCID 178418806, Verbindung

Produkt 1

HCID 1354069184,7-Dihydro-5-methyl-7-(1-methylethyl)pyrazolo[1,5-a]pyrimidine-6-carboxylic Acid 1,1-dimethylethyl EsterAusbeute 41,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
75 °C

Versuchsvorschrift

A pressure tube was dried with a heat gun under nitrogen. The pressure tube was charged in the following order with isobutyraldehyde 2(0.262 g, 3.63 mmol), dimethylformamide (3 mL), t-butylacetoacetate 1 (0.574 g, 3.63 mmol), 3-aminopyrazole 3 (0.362 g, 4.36 mmol) and sodium acetate (1.22 g, 14.5 mmol). The mixture was flushed with nitrogen. The tube was sealed and warmed to 75° C. and stirred overnight. The mixture was cooled to room temperature, diluted with ethyl acetate to a volume of 20 mL, washed with lithium chloride (2.4M, 10 mL) and brine, dried over anhydrous sodium sulfate, filtered and concentrated to give 1.02 of a yellow oil. The oil was purified by flash chromatography (silica, 45% ethyl acetate/heptane) to give 0.42 g (41% yield) of the title compound. Reverse Phase HPLC: YMC S5 ODS 4.6×50 mm Ballistic column, UV detection at 220λ, 4 min. gradient 0-100% Solvent B/A (Solvent A: 10% MeOH/H2O with 0.2% PPA, Solvent B: 90% MeOH/H2O with 0.2% PPA), 4 mL/min. Rt=3.83 min, (100% pure). Reverse Phase LC/MS: YMC S5 ODS 4.6×50 mm Ballistic column, UV detection at 220λ, 4 min. gradient 0-100% Solvent B/A (Solvent A: 10% MeOH/H2O with 0.1% TFA, Solvent B: 90% MeOH/H2O with 0.1% TFA), 4 mL/min. Rt=3.06 min. MS (EM, M+1: 278). HMR (CDCl3, 400 MHz): 7.37(1H,d,J=2.2 Hz), 6.35(1H,s), 5.55(1H,d,J=1.8 Hz), 5.29(1H,d,J=2.2 Hz), 2.41(3H,s), 1.50(9H,s), 1.28-1.19(1H,m), 1.07(3H,d,J=7.0 Hz), 0.60(3H,d,J=7.0 Hz).

Aufarbeitung

  1. customA pressure tube was dried with a heat gun under nitrogen
  2. customThe mixture was flushed with nitrogen
  3. customThe tube was sealed
  4. temperatureThe mixture was cooled to room temperature
  5. additiondiluted with ethyl acetate to a volume of 20 mL
  6. washwashed with lithium chloride (2.4M, 10 mL) and brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give 1.02 of a yellow oil
  11. customThe oil was purified by flash chromatography (silica, 45% ethyl acetate/heptane)

Quellen und Nachweise

ORD-Eintrag
ord-2d0ce4b777ca42dd8b5f9ac383d844e0
Quelldatensatz
uspto-grants-2004_03
Patentnummer
US06706720B2

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