Ethanol → HCID 44593932, compound

HRID 2384521Notes

Reaction equation

HRID 2384521 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:10](Br)=[C:9]([S:12]([C:15]3[CH:20]=[C:19]([F:21])[CH:18]=[C:17]([C:22]#[N:23])[CH:16]=3)(=[O:14])=[O:13])[S:8][C:5]2=[N:6][CH:7]=1.C(O)C.[F:27][C:28]1[CH:29]=[C:30](B(O)O)[CH:31]=[CH:32][CH:33]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.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>[NH2:1][C:2]1[CH:3]=[C:4]2[C:10]([C:32]3[CH:31]=[CH:30][CH:29]=[C:28]([F:27])[CH:33]=3)=[C:9]([S:12]([C:15]3[CH:20]=[C:19]([F:21])[CH:18]=[C:17]([C:22]#[N:23])[CH:16]=3)(=[O:14])=[O:13])[S:8][C:5]2=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 27339863-Fluorophenylboronic acidHCID 68521334HCID 68521334, compound

Product 1

HCID 44593932HCID 44593932, compoundYield 76%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Procedure

5-Amino-3-bromo-2-(3-cyano-5-fluoro-benzenesulfonyl)-thieno[2,3-b]pyridine (1.2 g, 29 mmol) was dissolved in toluene (16 ml) and ethanol (18 ml) under argon atmosphere. To the solution Pd(PPh3)4 (157 mg, 0.14 mmol), 3-fluorophenylboronic acid (0.50 g, 35.8 mmol) and 2M solution of Na2CO3 (14 ml) was added. The reaction mixture was refluxed for 1 hour then it was filtered through celite and washed with toluene. The filtrate was tightened in vacuum; water (13 ml) and ethyl acetate (13 ml) were added to the residue. It was separated and the water phase was extracted with ethyl acetate (2×5 ml). The organic phase was washed with water (5.0 ml), dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by column chromatography (Kieselgel 60, ethyl acetate:hexane=2:1) to yield 0.94 g (76%) of the title compound. The crude product can be purified by stirring with methanol to give a yellow amorphous material. LC-MS: (M+H)+ 428.2. 1H NMR (500 MHz, DMSO-d6, 25° C.): 5.67 (s, 2H); 6.81 (d, J=2.6 Hz, 1H); 7.00-7.07 (m, 2H); 7.35-7.43 (m, 1H); 7.50-7.60 (m, 2H); 7.60-7.64 (m, 1H); 8.20-8.25 (m, 1H); 8.27 (d, J=2.6 Hz, 1H).

Workup

  1. temperatureThe reaction mixture was refluxed for 1 hour
  2. filtrationit was filtered through celite
  3. washwashed with toluene
  4. additionwater (13 ml) and ethyl acetate (13 ml) were added to the residue
  5. customIt was separated
  6. extractionthe water phase was extracted with ethyl acetate (2×5 ml)
  7. washThe organic phase was washed with water (5.0 ml)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude product was purified by column chromatography (Kieselgel 60, ethyl acetate:hexane=2:1)

Sources & evidence

ORD record
ord-708aa6ee70cb421e8edab9d5cf33d8d5
Source dataset
uspto-grants-2012_09
Patent number
US08263773B2

Reaction notes

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