Methyl 4-aminobenzoate → Methyl 4-({cyclohexyl[3-methyl-6-(trifluoromethyl)thieno[3,2-b]pyridin-2-yl]methyl}amino)benzoate

HRID 2091326Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2091326
[CH:1]1([C:7]([C:9]2[S:17][C:16]3[C:11](=[N:12][CH:13]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:15]=3)[C:10]=2[CH3:22])=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:23][C:24]1[CH:33]=[CH:32][C:27]([C:28]([O:30][CH3:31])=[O:29])=[CH:26][CH:25]=1.C(=O)([O-])O.[Na+].C([BH3-])#N.[Na+]>O1CCCC1.[Ti](Cl)(Cl)(Cl)Cl.C(O)(=O)C.C(Cl)Cl.C(N(CC)CC)C>[CH:1]1([CH:7]([NH:23][C:24]2[CH:25]=[CH:26][C:27]([C:28]([O:30][CH3:31])=[O:29])=[CH:32][CH:33]=2)[C:9]2[S:17][C:16]3[C:11](=[N:12][CH:13]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:15]=3)[C:10]=2[CH3:22])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Komponenten

10

Edukt 4

HCID 12082Methyl 4-aminobenzoateHCID 516892Sodium Bicarbonate2×HCID 5003444Sodium cyanoborohydrideHCID 66778802Cyclohexyl[3-methyl-6-(trifluoromethyl)thieno[3,2-b]pyridin-2-yl]methanone

Produkt 1

HCID 66778478Methyl 4-({cyclohexyl[3-methyl-6-(trifluoromethyl)thieno[3,2-b]pyridin-2-yl]methyl}amino)benzoateAusbeute 68,1 %

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 24193Titanium TetrachlorideKatalysatorHCID 176Acetic AcidLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 8471TriethylamineLösungsmittel

Versuchsvorschrift

To a mixture of cyclohexyl[3-methyl-6-(trifluoromethyl)thieno[3,2-b]pyridin-2-yl]methanone (805 mg) synthesized above, methyl 4-aminobenzoate (410 mg), triethylamine (2.75 mL) and methylene chloride (10 mL) was added titanium (IV) chloride (323 μL) at 0° C., and the mixture was stirred at room temperature for 1 day under argon atmosphere. 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 (10 mL) of the obtained oil in tetrahydrofuran were added acetic acid (282 μL) and sodium cyanoborohydride (309 mg), and the mixture was stirred at room temperature for 1 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 (775 mg, 68%) as a pale-brown solid.

Aufarbeitung

  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 1 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)

Quellen und Nachweise

ORD-Eintrag
ord-3b80ecff70f54ee6884d71fae57a0636
Quelldatensatz
uspto-grants-2013_05
Patentnummer
US08436043B2

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