Acetic Acid → [2-Fluoro-6-(5-methoxy-benzofuran-2-yl)-pyridin-3-yl]-methyl-amine

HRID 501054Notes

Reaction equation

HRID 501054 reaction equation
[F:1][C:2]1[C:7]([NH2:8])=[CH:6][CH:5]=[C:4]([C:9]2[O:10][C:11]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:12]=3[CH:13]=2)[N:3]=1.C=O.[C:22](O)(=O)C.[BH3-]C#N.[Na+]>CO.ClC(Cl)C>[F:1][C:2]1[C:7]([NH:8][CH3:22])=[CH:6][CH:5]=[C:4]([C:9]2[O:10][C:11]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:12]=3[CH:13]=2)[N:3]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 250150202-Fluoro-6-(5-methoxy-benzofuran-2-yl)-pyridin-3-ylamine

Product 1

HCID 59424801[2-Fluoro-6-(5-methoxy-benzofuran-2-yl)-pyridin-3-yl]-methyl-amineYield 34.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 63651,1-DichloroethaneSolvent

Procedure

To a stirred solution of 2-fluoro-6-(5-methoxy-benzofuran-2-yl)-pyridin-3-ylamine (97 mg, 0.376 mmol) in a mixture of MeOH (2 mL) and dichloroethane (1 mL), formaldehyde (37% solution in water, 0.167 mL, 2.23 mmol) and acetic acid (50 μL, 0.87 mmol) were added. The reaction mixture was stirred for 2 hours at room temperature, then NaCNBH3 (94 mg, 1.50 mmol) was added in one portion and the stirring was continued for 45 minutes. The reaction was then quenched by addition of water (2 mL). The volatiles were removed under reduced pressure and the residue was extracted with dichloromethane (50 mL). The organic layer was washed with water, dried over Na2SO4, filtered and concentrated. The product was purified by flash column chromatography using 20% ethyl acetate in hexane to afford [2-fluoro-6-(5-methoxy-benzofuran-2-yl)-pyridin-3-yl]-methyl-amine (35.7 mg) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ: 7.64 (d, J=8.2 Hz, 1H), 7.38 (d, J=8.98 Hz, 1H), 7.09 (s, 1H), 7.03 (d, J=2.34 Hz, 1H), 6.99 (dd, J=10.15, 8.20 Hz, 1H), 6.87 (dd, J=8.78, 2.54 Hz, 1H), 4.21 (br. s, 1H), 3.85 (s, 3H), 2.94 (d, J=5.07 Hz, 3H)

Workup

  1. additionwere added
  2. waitthe stirring was continued for 45 minutes
  3. customThe reaction was then quenched by addition of water (2 mL)
  4. customThe volatiles were removed under reduced pressure
  5. extractionthe residue was extracted with dichloromethane (50 mL)
  6. washThe organic layer was washed with water
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe product was purified by flash column chromatography

Sources & evidence

ORD record
ord-e9220dee3c784890bbf68230e74b7169
Source dataset
uspto-grants-2010_08
Patent number
US07772256B2

Reaction notes

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