Hydrochloric Acid → N-Methyl-5-(3-pyridinyl)-2-furanmethanamine

HRID 1913361Notes

Reaction equation

HRID 1913361 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[O:11][C:10]([CH:12]=O)=[CH:9][CH:8]=2)[CH:2]=1.CN.Cl.[C:17]([BH3-])#[N:18].[Na+]>CO.O1CCOCC1>[CH3:17][NH:18][CH2:12][C:10]1[O:11][C:7]([C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)=[CH:8][CH:9]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6329MethylamineHCID 5003444Sodium cyanoborohydrideHCID 122152605-(Pyridin-3-yl)furan-2-carbaldehyde

Product 1

HCID 11229234N-Methyl-5-(3-pyridinyl)-2-furanmethanamineYield 84%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution 23 (104 mg, 0.60 mmol) was added a solution of methylamine (2.0 M, 1.8 mL, 3.6 mmol) in anhydrous CH3OH, a solution of HCl (4.0 M, 0.3 mL, 1.2 mmol) in anhydrous 1,4-dioxane and sodium cyanoborohydride (38 mg, 0.6 mmol). The flask was purged with argon and stirred under an atmosphere of argon at room temperature for 48 h. The solution was adjusted to pH 2 with conc. HCl and the solvent was removed in vacuo. The residue was dissolved in water, washed with Et2O (3×10 mL), adjusted to pH 10 with NaOH(aq) (10 N), extracted with Et2O (3×20 mL), dried (Na2SO4), filtered and the solvent was removed in vacuo. The crude material was chromatographed on silica gel (CH3OH/CHCl3, 10/90, Rf=0.1) to afford the title compound 41 (94 mg, 84% yield) as a yellow oil: 1H NMR (CDCl3) δ 8.89 (m, 1H), 8.46 (m, 1H), 7.91 (m, 1H), 7.28 (m, 1H), 6.67 (d, J=3.2 Hz, 1H), 6.31 (d, J=3.2 Hz, 1H), 3.82 (s, 2H), 2.49 (s, 3H), 2.14 (br s, 1H); LRMS (ESI) m/z calcd for C11H13N2O [M+H]+ 189. found 189; m/z calcd for C10H8NO [M−NH(CH3)]+ 158. found 158; HRMS (ESI) m/z calcd for C11H13N2O [M+H]+ 189.1028. found 189.1041; HPLC>95% (tR=8.74 min, 60 (A):40 (B): 0.02 (C); tR=3.69 min, 60 (A):40 (B): 0.07 (C)).

Workup

  1. customThe flask was purged with argon
  2. customthe solvent was removed in vacuo
  3. dissolutionThe residue was dissolved in water
  4. washwashed with Et2O (3×10 mL)
  5. extractionextracted with Et2O (3×20 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customthe solvent was removed in vacuo
  9. customThe crude material was chromatographed on silica gel (CH3OH/CHCl3, 10/90, Rf=0.1)

Sources & evidence

ORD record
ord-6c97c7179aa042e483cc0337f5e9f852
Source dataset
uspto-grants-2013_12
Patent number
US08609708B2

Reaction notes

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