2,6-Difluoroaniline → HCID 178480680, Verbindung

HRID 1516362Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1516362
ClC(Cl)(O[C:5](=[O:11])OC(Cl)(Cl)Cl)Cl.Cl.Cl.C(OC([N:20]1[C:24]([NH:25][C:26](=[O:40])[C:27]2[CH:32]=[CH:31][C:30]([N:33]3[CH2:38][CH2:37][N:36]([CH3:39])[CH2:35][CH2:34]3)=[CH:29][CH:28]=2)=[C:23]2[CH2:41][NH:42][C:43]([CH3:45])([CH3:44])[C:22]2=[N:21]1)=O)C.C(N(CC)C(C)C)(C)C.[F:55][C:56]1[CH:61]=[CH:60][CH:59]=[C:58]([F:62])[C:57]=1[NH2:63]>C(Cl)Cl>[F:55][C:56]1[CH:61]=[CH:60][CH:59]=[C:58]([F:62])[C:57]=1[NH:63][C:5]([N:42]1[CH2:41][C:23]2[C:22](=[N:21][NH:20][C:24]=2[NH:25][C:26](=[O:40])[C:27]2[CH:28]=[CH:29][C:30]([N:33]3[CH2:38][CH2:37][N:36]([CH3:39])[CH2:35][CH2:34]3)=[CH:31][CH:32]=2)[C:43]1([CH3:44])[CH3:45])=[O:11]

Komponenten

6

Edukt 4

HCID 796472,6-DifluoroanilineHCID 81531Diisopropylethylamine2×HCID 94429TriphosgeneHCID 672375746,6-Dimethyl-3-[4-(4-methyl-piperazin-1-yl)-benzoylamino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-2-carboxylic acid ethyl ester dihydrochloride

Produkt 1

HCID 178480680HCID 178480680, VerbindungAusbeute 111,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel3×

Versuchsvorschrift

To a solution of triphosgene (195 mg, 0.65 mmol, 0.56 eq) in DCM (15 mL) was added a solution of 6,6-Dimethyl-3-[4-(4-methyl-piperazin-1-yl)-benzoylamino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-2-carboxylic acid ethyl ester dihydrochloride (0.60 g, 1.15 mmol) in DCM (30 mL) followed by N,N-diisopropylethylamine (760 microL, 4.31 mmol, 3.75 eq). After 3 hours, a solution of 2,6-Difluoro-phenylamine (0.22, 1.72 mmol, 1.5 eq) and diisopropylethylamine (300 microL, 1.72 mmol, 1.5 eq) in DCM (8 mL) was added. The reaction was stirred overnight at room temperature. The solution was washed with brine, the organic phase was dried over sodium sulphate and concentrated. The residue was dissolved in methanol (16 mL), treated with TEA (1.6 mL, 11.5 mmol, 10 eq) and stirred overnight at room temperature. After evaporation of the solvent, the solid was purified by flash chromatography (CH2Cl2/MeOH/NH3 95/5/01). The solid was treated with diisopropylether and filtered to afford 0.37 g of the title compound in 64% yield.

Aufarbeitung

  1. washThe solution was washed with brine
  2. dry with materialthe organic phase was dried over sodium sulphate
  3. concentrationconcentrated
  4. dissolutionThe residue was dissolved in methanol (16 mL)
  5. stirringstirred overnight at room temperature
  6. customAfter evaporation of the solvent
  7. customthe solid was purified by flash chromatography (CH2Cl2/MeOH/NH3 95/5/01)
  8. additionThe solid was treated with diisopropylether
  9. filtrationfiltered

Quellen und Nachweise

ORD-Eintrag
ord-170783c5eeb145e7bafc0503ba973890
Quelldatensatz
uspto-grants-2012_07
Patentnummer
US08227472B2

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