Potassium Carbonate → 7-[3-(1,1-Dioxido-1,2-thiazolidin-2-yl)phenyl]-2-(methylsulfanyl)pyrrolo[2,1-f][1,2,4]triazine

HRID 1262410

Reaktionsgleichung

Reaktionsgleichung von HRID 1262410
[CH3:1][S:2][C:3]1[N:8]=[CH:7][C:6]2=[CH:9][CH:10]=[C:11]([C:12]3[CH:13]=[C:14]([NH2:18])[CH:15]=[CH:16][CH:17]=3)[N:5]2[N:4]=1.C(N(CC)C(C)C)(C)C.C(=O)([O-])[O-].[K+].[K+].Cl[CH2:35][CH2:36][CH2:37][S:38](Cl)(=[O:40])=[O:39]>CN(C)C=O.CCOC(C)=O.O>[O:39]=[S:38]1(=[O:40])[CH2:37][CH2:36][CH2:35][N:18]1[C:14]1[CH:13]=[C:12]([C:11]2[N:5]3[C:6]([CH:7]=[N:8][C:3]([S:2][CH3:1])=[N:4]3)=[CH:9][CH:10]=2)[CH:17]=[CH:16][CH:15]=1

Komponenten

8

Edukt 4

HCID 11430Potassium CarbonateHCID 154103-Chloropropanesulphonyl chloride2×HCID 81531Diisopropylethylamine2×HCID 667126823-(2-Methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-phenylamine

Produkt 1

HCID 667117407-[3-(1,1-Dioxido-1,2-thiazolidin-2-yl)phenyl]-2-(methylsulfanyl)pyrrolo[2,1-f][1,2,4]triazineAusbeute 46,5 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

3-(2-Methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-phenylamine (0.795 g, 3.10 mmol) was dissolved in N,N-Dimethylformamide (12.0 mL) and N,N-Diisopropylethylamine (1.50 mL, 8.61 mmol). Potassium carbonate (1.28 g, 9.30 mmol) was added, followed by 3-Chloropropane-1-sulfonyl chloride (0.450 mL, 3.70 mmol) and stirred overnight. After 24 h, a second aliquot of N,N-Diisopropylethylamine (2.00 mL, 11.5 mmol) and 3-Chloropropane-1-sulfonyl chloride (0.50 mL, 4.1 mmol) was added and stirred additionally. When conversion had reached ca. 90%, the mixture was treated with water (40 mL) and EtOAc (40 mL). The layers were separated, the aq. extr. with EtOAc (3×20 mL) and the comb. org. diluted with hexane (20 mL) and washed with water (30 ml) and brine (30 mL). After drying over sodium sulfate, the mixture was filtered and conc. in vacuo and applied to a 25 g ISCO loading cartridge. Purification on ISCO (40 g column, 10-70% EtOAc:Hex) afforded 7-[3-(1,1-Dioxido-1,2-thiazolidin-2-yl)phenyl]-2-(methylsulfanyl)pyrrolo[2,1-f][1,2,4]triazine (0.52 g; Yield=46%) as a yellow solid. 1H-NMR (CDCl3): 8.74 (s, 1H), 8.06 (s, 1H), 7.86 (d, 1H, J=7.9 Hz), 7.47 (m, 1H), 7.28 (m, 1H), 7.27 (s, 1H), 7.12 (d, 1H, J=4.8 Hz), 6.89 (d, 1H, J=4.8 Hz), 3.86 (t, 2H, J=6.5 Hz), 3.42 (t, 2H, J=7.4 Hz), 2.62 (s, 3H), 2.58 (m, 2H).

Aufarbeitung

  1. waitAfter 24 h
  2. stirringstirred additionally
  3. customThe layers were separated
  4. additiondiluted with hexane (20 mL)
  5. washwashed with water (30 ml) and brine (30 mL)
  6. dry with materialAfter drying over sodium sulfate
  7. filtrationthe mixture was filtered and conc. in vacuo
  8. customPurification on ISCO (40 g column, 10-70% EtOAc:Hex)

Quellen und Nachweise

ORD-Eintrag
ord-efe2dbe425ee4d9d9349e5f0f34b9030
Quelldatensatz
uspto-grants-2013_06
Patentnummer
US08471005B2

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