Sodium Chloride → 3-(4-Phenoxyphenyl)thieno[3,2-c]pyridin-4-amine

HRID 1270863Notes

Reaction equation

HRID 1270863 reaction equation
Br[C:2]1[C:6]2[C:7]([NH2:11])=[N:8][CH:9]=[CH:10][C:5]=2[S:4][CH:3]=1.[O:12]([C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][CH:20]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C([O-])([O-])=O.[Na+].[Na+].[Na+].[Cl-]>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.O.CN(C=O)C>[O:12]([C:19]1[CH:20]=[CH:21][C:22]([C:2]2[C:6]3[C:7]([NH2:11])=[N:8][CH:9]=[CH:10][C:5]=3[S:4][CH:3]=2)=[CH:23][CH:24]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

8

Reactant 4

HCID 5234Sodium ChlorideHCID 10340Sodium CarbonateHCID 27343774-Phenoxyphenylboronic acidHCID 184507973-Bromothieno[3,2-c]pyridin-4-amine

Product 1

HCID 184507633-(4-Phenoxyphenyl)thieno[3,2-c]pyridin-4-amineYield 75%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of Example 219A (5.43 g, 23.7 mmol), 4-phenoxyphenylboronic acid (6 g, 28.03 mmol), Na2CO3 (3.7 g, 34.9 mmol), Pd(PPh3)4 (5.4 g, 4.7 mmol), DMF (96 mL), and water (24 mL) was stirred for 18 hours at 80° C. under nitrogen, poured into 10% aqueous NaCl (400 mL), and extracted with ethyl acetate (3×70 mL). The combined organic extracts were washed with brine, dried (MgSO4), filtered, and concentrated under reduced pressure. The residue was dissolved in 300 mL of dichloromethane. Silica gel (90 g) was added to the solution and the mixture was concentrated under vacuum. The residual silica gel with the absorbed crude product was transferred to a silica gel column (600 g) and chromatographed (eluent 40% ethyl acetate/heptane) to provide 5.61 g (75%) of the desired product. 1H NMR (DMSO-d6, 400 MHz) δ 7.85 (d, 1H), 7.49–7.44 (m, 5H), 7.29 (d, 1H), 7.22 (t, 1H), 7.16–7.12 (m, 4H), 5.44 (br s, 2H); 13C NMR (DMSO-d6, 100 MHz) δ 156.9, 156.1, 154.5, 148.3, 141.8, 136.1, 130.9, 130.1, 123.9, 123.0, 119.2, 118.4, 118.1, 107.8.

Workup

  1. extractionextracted with ethyl acetate (3×70 mL)
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe residue was dissolved in 300 mL of dichloromethane
  7. additionSilica gel (90 g) was added to the solution
  8. concentrationthe mixture was concentrated under vacuum
  9. customThe residual silica gel with the absorbed crude product
  10. customchromatographed (eluent 40% ethyl acetate/heptane)

Sources & evidence

ORD record
ord-728481a13c1b4e1eb34a3779fb74e86d
Source dataset
uspto-grants-2007_04
Patent number
US07202363B2

Reaction notes

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