1,4-Dioxane → HCID 67345312, compound

HRID 1676284Notes

Reaction equation

HRID 1676284 reaction equation
[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][N:24]([CH2:27][C:28]2[O:29][C:30]([Sn](CCCC)(CCCC)CCCC)=[CH:31][CH:32]=2)[CH2:23][CH2:22]1.O1CCOCC1>[Cl-].[Na+].O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:1][C:2]1[CH:3]=[C:4]([NH2:5])[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]([C:30]3[O:29][C:28]([CH2:27][N:24]4[CH2:23][CH2:22][N:21]([CH3:20])[CH2:26][CH2:25]4)=[CH:32][CH:31]=3)[S:18][C:11]=12

Participants

6

Reactant 3

HCID 312751,4-DioxaneHCID 584749503-Fluoro-4-((2-iodothieno[3,2-b]pyridin-7-yl)oxy)anilineHCID 67347378HCID 67347378, compound

Product 1

HCID 67345312HCID 67345312, compoundYield 63.3%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
90 °C

Procedure

A round-bottomed flask was charged with 3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)benzenamine (Example 6, Step A; 0.600 g, 1.55 mmol), 1-methyl-4-((5-(tributylstannyl)furan-2-yl)methyl)piperazine (0.802 g, 1.71 mmol), PdCl2(PPh3)2 (0.050 g, 0.075 mmol), and dioxane (8 mL). The reaction mixture was heated to 90° C. for 18 hours under nitrogen and then cooled to room temperature. The reaction mixture was diluted with brine (100 mL) and extracted with EtOAc (100 mL). The combined organic layers were dried over sodium sulfate, filter and concentrated. The residue was purified by Biotage 40S eluting with CHCl3/MeOH saturated NH3. (95:5) to provide 430 mg (60%) of the product as a light green solid. 1H NMR (CDCl3, 400 MHz). δ 8.43 (d, J=5.5 Hz, 1H), 7.62 (s, 1H), 7.03 (t, J=8.6 Hz, 1H), 6.69 (d, J=3.5 Hz, 1H), 6.48 (m, 3H), 6.34 (d, J=3.1 Hz, 1H), 3.88 (s, 2H), 3.66 (s, 2H), 2.61 (m, 8H), 2.29 (s, 3H).

Workup

  1. temperaturecooled to room temperature
  2. extractionextracted with EtOAc (100 mL)
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. filtrationfilter
  5. concentrationconcentrated
  6. customThe residue was purified by Biotage 40S
  7. washeluting with CHCl3/MeOH saturated NH3

Sources & evidence

ORD record
ord-57d1480a002742688585b0036e149a50
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

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