Sodium Carbonate → 4-(2-(1,4-Dioxaspiro[4.5]dec-7-en-8-yl)thieno[3,2-b]pyridin-7-yloxy)-3-fluoroaniline

HRID 1676371Notes

Reaction equation

HRID 1676371 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].[O:20]1[C:24]2([CH2:29][CH2:28][C:27](B(O)O)=[CH:26][CH2:25]2)[O:23][CH2:22][CH2:21]1.C([O-])([O-])=O.[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCOCC1>[O:20]1[C:24]2([CH2:29][CH2:28][C:27]([C:17]3[S:18][C:11]4[C:12](=[N:13][CH:14]=[CH:15][C:10]=4[O:9][C:8]4[CH:7]=[CH:6][C:4]([NH2:5])=[CH:3][C:2]=4[F:1])[CH:16]=3)=[CH:26][CH2:25]2)[O:23][CH2:22][CH2:21]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 441187651,4-Dioxaspiro[4.5]dec-7-en-8-ylboronic acidHCID 584749503-Fluoro-4-((2-iodothieno[3,2-b]pyridin-7-yl)oxy)aniline

Product 1

HCID 673482014-(2-(1,4-Dioxaspiro[4.5]dec-7-en-8-yl)thieno[3,2-b]pyridin-7-yloxy)-3-fluoroanilineYield 88.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A round-bottomed flask was charged with 3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)aniline (Example 6, Step A, 0.461 g, 1.19 mmol), 1,4-dioxaspiro[4.5]dec-7-en-8-ylboronic acid (0.659 g, 3.58 mmol), tetrakis(triphenylphosphine)palladium (0.276 g, 0.239 mmol), Na2CO3 (2.98 ml, 5.97 mmol) and dioxane (50 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 50/1 to 10/1, v/v) to afford product (0.418 g, 87.9%). LRMS (APCI pos): >97% purity, 254 nm, m/e 399 (M+1). 1H NMR (400 MHz, CDCl3) δ 8.40 (d, 1H), 7.34 (s, 1H), 7.01 (t, 1H), 6.42-6.56 (m, 3H), 6.28 (s, 1H), 4.04 (s, 4H), 3.82 (br s, 2H), 2.80 (m, 2H), 2.52 (m, 2H), 1.98 (m, 2H).

Workup

  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 50/1 to 10/1

Sources & evidence

ORD record
ord-c20b389127124f5ea268e231456ccfba
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

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