2,2-Dimethyl-1,3-dioxane-4,6-dione → 1-(3-(trifluoromethyl)-5,6-dihydro(1,2,4)triazolo(4,3-a)pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione

HRID 1432130

Reaktionsgleichung

Reaktionsgleichung von HRID 1432130
[F:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([F:9])=[CH:4][C:3]=1[CH2:10][C:11]([OH:13])=O.C[C:15]1([CH3:23])[O:22]C(=O)CC(=O)O1.C(N(CC)C(C)C)(C)C.C(Cl)(=O)C(C)(C)C.Cl.[F:41][C:42]([F:53])([F:52])[C:43]1[N:47]2[CH2:48][CH2:49][NH:50][CH2:51][C:46]2=[N:45][N:44]=1.C(=O)([O-])O.[Na+]>CN(C)C1C=CN=CC=1.CN(C)C(=O)C>[O:22]=[C:15]([N:50]1[CH2:49][CH2:48][N:47]2[C:43]([C:42]([F:53])([F:41])[F:52])=[N:44][N:45]=[C:46]2[CH2:51]1)[CH2:23][C:11](=[O:13])[CH2:10][C:3]1[CH:4]=[C:5]([F:9])[C:6]([F:8])=[CH:7][C:2]=1[F:1]

Komponenten

9

Edukt 6

HCID 162492,2-Dimethyl-1,3-dioxane-4,6-dioneHCID 62493Pivaloyl chlorideHCID 81531DiisopropylethylamineHCID 516892Sodium Bicarbonate2×HCID 27779502,4,5-Trifluorophenylacetic acidHCID 119613713-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride

Produkt 1

HCID 98875881-(3-(trifluoromethyl)-5,6-dihydro(1,2,4)triazolo(4,3-a)pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 31374DimethylacetamideLösungsmittel

Reaktionsbedingungen

Temperatur
2.5 °C

Versuchsvorschrift

2,4,5-Trifluorophenylacetic acid (2-1) (150 g, 0.789 mol), Meldrum's acid (125 g, 0.868 mol), and 4-(dimethylamino)pyridine (DMAP) (7.7 g, 0063 mol) were charged into a 5 L three-neck flask. N,N-Dimethylacetamide (Mac) (525 mL) was added in one portion at room temperature to dissolve the solids. N,N-diisopropylethylamine (282 mL, 1.62 mol) was added in one portion at room temperature while maintaining the temperature below 40° C. Pivaloyl chloride (107 mL, 0.868 mol) was added dropwise over 1 to 2 h while maintaining the temperature between 0 and 5° C. The reaction mixture was aged at 5° C. for 1 h. Triazole hydrochloride 1-4 (180 g, 0.789 mol) was added in one portion at 40-50° C. The reaction solution was aged at 70° C. for several h. 5% Aqueous sodium hydrogencarbonate solution (625 mL) was then added dropwise at 20-45° C. The batch was seeded and aged at 20-30° C. for 1-2 h. Then an additional 525 mL of 5% aqueous sodium hydrogencarbonate solution was added dropwise over 2-3 h. After aging several h at room temperature, the slurry was cooled to 0-5° C. and aged 1 h before filtering the solid. The wet cake was displacement-washed with 20% aqueous Mac (300 mL), followed by an additional two batches of 20% aqueous Mac (400 mL), and finally water (400 mL). The cake was suction-dried at room temperature. The isolated yield of final product 2-3 was 89%.

Aufarbeitung

  1. dissolutionto dissolve the solids
  2. temperaturewhile maintaining the temperature below 40° C
  3. temperaturewhile maintaining the temperature between 0 and 5° C
  4. customwas aged at 70° C. for several h
  5. waitaged at 20-30° C. for 1-2 h
  6. customat room temperature
  7. filtrationbefore filtering the solid
  8. washThe wet cake was displacement-washed with 20% aqueous Mac (300 mL)
  9. customThe cake was suction-dried at room temperature

Quellen und Nachweise

ORD-Eintrag
ord-da4416beebc54a998595e7bf3485cb48
Quelldatensatz
uspto-grants-2009_11
Patentnummer
US07612072B2

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