Potassium Carbonate → 3-Fluoro-4-(2-(4-methylpiperazin-1-yl)thieno[3,2-b]pyridin-7-yloxy)aniline

HRID 1676361Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1676361
[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[O:9][C:10]1[CH:15]=[CH:14][N:13]=[C:12]2[CH:16]=[C:17](I)[S:18][C:11]=12)[NH2:5].[CH3:20][N:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1.N1CCC[C@H]1C(O)=O.C([O-])([O-])=O.[K+].[K+]>[Cu]I.CS(C)=O>[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[O:9][C:10]1[CH:15]=[CH:14][N:13]=[C:12]2[CH:16]=[C:17]([N:24]3[CH2:25][CH2:26][N:21]([CH3:20])[CH2:22][CH2:23]3)[S:18][C:11]=12)[NH2:5]

Komponenten

7

Edukt 4

HCID 11430Potassium CarbonateHCID 531671-MethylpiperazineHCID 145742L-ProlineHCID 584749503-Fluoro-4-((2-iodothieno[3,2-b]pyridin-7-yl)oxy)aniline

Produkt 1

HCID 673478913-Fluoro-4-(2-(4-methylpiperazin-1-yl)thieno[3,2-b]pyridin-7-yloxy)anilineAusbeute 85,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 679Dimethyl SulfoxideLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A round-bottomed flask was charged with 3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)aniline (Example 6, Step A, 200.0 mg, 0.518 mmol), 1-methyl piperazine (0.172 ml, 1.55 mmol), copper(I) iodide (29.59 mg, 0.155 mmol), (S) -pyrrolidine-2-carboxylic acid (17.89 mg, 0.155 mmol), K2CO3 (357.9 mg, 2.59 mmol) and DMSO (25 mL). The reaction mixture was stirred at 100° C. until the starting material had been consumed (overnight). Then the reaction was cooled to room temperature and partitioned between EtOAc (100 mL) and H2O (100 mL). The phases were separated and the aqueous phase was re-extracted with EtOAc (3×100 mL). The combined organic layers were dried (Na2SO4), filtered and concentrated to yield a crude product. The crude product was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 100/1 to 10/1, v/v) to afford product (158.5 mg, 85%). LRMS (APCI pos): >95% purity, 254 nm, m/e 359.3 (M+1). 1H NMR (400 MHz, CD3OD) δ 8.11 (d, 1H), 6.96 (t, 1H), 6.53 (dd, 1H), 6.49 (m, 1H), 6.29 (m, 2H), 3.36 (m, 4H), 2.60 (m, 4H), 2.33 (s, 3H).

Aufarbeitung

  1. customhad been consumed (overnight)
  2. temperatureThen the reaction was cooled to room temperature
  3. custompartitioned between EtOAc (100 mL) and H2O (100 mL)
  4. customThe phases were separated
  5. extractionthe aqueous phase was re-extracted with EtOAc (3×100 mL)
  6. dry with materialThe combined organic layers were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto yield a crude product
  10. customThe crude product was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 100/1 to 10/1

Quellen und Nachweise

ORD-Eintrag
ord-9a3075a610e149a3841ff9b3a7319f65
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US08003662B2

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