Sodium Hydroxide → 7-(3,5-bis-trifluoromethyl-benzylamino)-5-ethyl-6,7-dihydro-5H-thieno[3,2-b]pyridine-4-carboxylic acid isopropyl ester

HRID 2378099

Reaction equation

HRID 2378099 reaction equation
[CH:1]([O:4][C:5]([N:7]1[CH:12]([CH2:13][CH3:14])[CH2:11][C:10](=O)[C:9]2[S:16][CH:17]=[CH:18][C:8]1=2)=[O:6])([CH3:3])[CH3:2].[F:19][C:20]([F:34])([F:33])[C:21]1[CH:22]=[C:23]([CH:26]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:28]=1)[CH2:24][NH2:25].C([BH3-])#N.[Na+].[BH4-].[Na+].[OH-].[Na+]>CO.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[CH:1]([O:4][C:5]([N:7]1[CH:12]([CH2:13][CH3:14])[CH2:11][CH:10]([NH:25][CH2:24][C:23]2[CH:26]=[C:27]([C:29]([F:30])([F:31])[F:32])[CH:28]=[C:21]([C:20]([F:19])([F:33])[F:34])[CH:22]=2)[C:9]2[S:16][CH:17]=[CH:18][C:8]1=2)=[O:6])([CH3:3])[CH3:2]

Participants

8

Reactant 5

HCID 14798Sodium HydroxideHCID 5210993,5-Bis(trifluoromethyl)benzylamineHCID 4311764Sodium borohydrideHCID 5003444Sodium cyanoborohydride2×HCID 589267625-ethyl-7-oxo-6,7-dihydro-5H-thieno[3,2-b]pyridine-4-carboxylic acid isopropyl ester

Product 1

HCID 589267187-(3,5-bis-trifluoromethyl-benzylamino)-5-ethyl-6,7-dihydro-5H-thieno[3,2-b]pyridine-4-carboxylic acid isopropyl esterYield 75.7%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 887MethanolSolvent2×

Procedure

Inject titanium(IV)isopropoxide (0.372 ml, 1.26 mmol) to a mixture of 5-ethyl-7-oxo-6,7-dihydro-5H-thieno[3,2-b]pyridine-4-carboxylic acid isopropyl ester (0.225 g, 0.842 mmol), 3,5-bis(trifluoromethyl)benzylamine (0.211 g, 0.842 mmol), and then stir at room temperature for 4 h. Inject a solution of sodium cyanoborohydride (0.212 g, 3.37 mmol) in methanol (8 ml) to the reaction mixture and continue to stir at room temperature overnight. Add another portion of solution of sodium cyanoborohydride (0.212 g, 3.37 mmol) in methanol (8 ml) and continue to stir for 4 h. Add sodium borohydride (0.159 g, 4.21 mmol) and heat the reaction at 60° C. overnight. Treat the mixture with 0.1 N sodium hydroxide (25 ml) for 10 minutes, and then filter through a Celite® pad. Wash the filtered residue thoroughly with ethyl acetate. Separate the organic layer, wash with brine (3×50 ml), dry over Na2SO4, filter and concentrate to provide crude 7-(3,5-bis-trifluoromethyl-benzylamino)-5-ethyl-6,7-dihydro-5H-thieno [3,2-b]pyridine-4-carboxylic acid isopropyl ester (0.315 g) which was elaborated without further purification. MS (ES+): 495 (M+H).

Workup

  1. stirringto stir at room temperature overnight
  2. stirringto stir for 4 h
  3. customthe reaction at 60° C. overnight
  4. filtrationfilter through a Celite® pad
  5. washWash the filtered residue thoroughly with ethyl acetate
  6. customSeparate the organic layer
  7. washwash with brine (3×50 ml)
  8. dry with materialdry over Na2SO4
  9. filtrationfilter
  10. concentrationconcentrate

Sources & evidence

ORD record
ord-fb0df5a283c74863b2d09c5f91e29391
Source dataset
uspto-grants-2008_12
Patent number
US07470705B2

Linked notes

Loading…