Methyl 4-aminobenzoate → Methyl 4-{[(5-bromo-3-methylfuro[3,2-b]pyridin-2-yl)(cyclohexyl)methyl]amino}benzoate

HRID 2091251Notes

Reaction equation

HRID 2091251 reaction equation
[Br:1][C:2]1[N:7]=[C:6]2[C:8]([CH3:19])=[C:9]([C:11]([CH:13]3[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]3)=O)[O:10][C:5]2=[CH:4][CH:3]=1.[NH2:20][C:21]1[CH:30]=[CH:29][C:24]([C:25]([O:27][CH3:28])=[O:26])=[CH:23][CH:22]=1.C(=O)([O-])O.[Na+].C([BH3-])#N.[Na+]>C(Cl)Cl.O1CCCC1.[Ti](Cl)(Cl)(Cl)Cl.C(O)(=O)C.C(N(CC)CC)C>[Br:1][C:2]1[N:7]=[C:6]2[C:8]([CH3:19])=[C:9]([CH:11]([NH:20][C:21]3[CH:22]=[CH:23][C:24]([C:25]([O:27][CH3:28])=[O:26])=[CH:29][CH:30]=3)[CH:13]3[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]3)[O:10][C:5]2=[CH:4][CH:3]=1

Participants

10

Reactant 4

HCID 12082Methyl 4-aminobenzoateHCID 516892Sodium Bicarbonate2×HCID 5003444Sodium cyanoborohydrideHCID 86662737(5-Bromo-3-methylfuro[3,2-b]pyridin-2-yl)(cyclohexyl)methanone

Product 1

HCID 86662738Methyl 4-{[(5-bromo-3-methylfuro[3,2-b]pyridin-2-yl)(cyclohexyl)methyl]amino}benzoateYield 90%

Reagents, catalysts & solvents 5

HCID 24193Titanium TetrachlorideCatalystHCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

To a mixture of (5-bromo-3-methylfuro[3,2-b]pyridin-2-yl)(cyclohexyl)methanone (1.46 g) synthesized above, methyl 4-aminobenzoate (753 mg), triethylamine (5.05 mL) and methylene chloride (15 mL) was added a 1.0M solution (5.44 mL) of titanium (IV) chloride in methylene chloride at 0° C., and the mixture was stirred under argon atmosphere overnight at room temperature. Saturated aqueous sodium hydrogen carbonate solution was added to quench the reaction, and the reaction mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure to give a dark brown oil. To a solution (20 mL) of the obtained oil in tetrahydrofuran were added acetic acid (1.30 mL) and sodium cyanoborohydride (569 mg), and the mixture was stirred at room temperature for 2 hr. Saturated aqueous sodium hydrogen carbonate solution was added to quench the reaction, and the reaction mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (0-40% ethyl acetate/hexane) to give the title object compound (1.86 g, 90%) as a pale-brown solid.

Workup

  1. customto quench
  2. customthe reaction
  3. extractionthe reaction mixture was extracted with ethyl acetate
  4. washThe extract was washed with saturated brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customto give a dark brown oil
  8. stirringthe mixture was stirred at room temperature for 2 hr
  9. customto quench
  10. customthe reaction
  11. extractionthe reaction mixture was extracted with ethyl acetate
  12. washThe extract was washed with saturated brine
  13. dry with materialdried over magnesium sulfate
  14. concentrationconcentrated under reduced pressure
  15. customThe residue was purified by silica gel column chromatography (0-40% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-94183bfb33744b388932844c26f7f11a
Source dataset
uspto-grants-2013_05
Patent number
US08436043B2

Reaction notes

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