Hydrochloric Acid → 6-(1-((6-Cyclopropyl-3-ethoxy-2,4'-difluorobiphenyl-4-yl)methyl)piperidin-4-yl)-2-ethyl-5-oxo-5,6,7,8-tetrahydro-1,6-naphthyridine-3-carboxylic acid

HRID 531116Notes

Reaction equation

HRID 531116 reaction equation
[OH-].[Na+].[CH:3]1([C:6]2[C:11]([C:12]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=3)=[C:10]([F:19])[C:9]([O:20][CH2:21][CH3:22])=[C:8]([CH2:23][N:24]3[CH2:29][CH2:28][CH:27]([N:30]4[CH2:39][CH2:38][C:37]5[N:36]=[C:35]([CH2:40][CH3:41])[C:34]([C:42]([O:44]C)=[O:43])=[CH:33][C:32]=5[C:31]4=[O:46])[CH2:26][CH2:25]3)[CH:7]=2)[CH2:5][CH2:4]1.Cl>CO>[CH:3]1([C:6]2[C:11]([C:12]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=3)=[C:10]([F:19])[C:9]([O:20][CH2:21][CH3:22])=[C:8]([CH2:23][N:24]3[CH2:25][CH2:26][CH:27]([N:30]4[CH2:39][CH2:38][C:37]5[N:36]=[C:35]([CH2:40][CH3:41])[C:34]([C:42]([OH:44])=[O:43])=[CH:33][C:32]=5[C:31]4=[O:46])[CH2:28][CH2:29]3)[CH:7]=2)[CH2:5][CH2:4]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 117992049Methyl 6-(1-((6-cyclopropyl-3-ethoxy-2,4'-difluorobiphenyl-4-yl)methyl)piperidin-4-yl)-2-ethyl-5-oxo-5,6,7,8-tetrahydro-1,6-naphthyridine-3-carboxylate

Product 1

HCID 1179921346-(1-((6-Cyclopropyl-3-ethoxy-2,4'-difluorobiphenyl-4-yl)methyl)piperidin-4-yl)-2-ethyl-5-oxo-5,6,7,8-tetrahydro-1,6-naphthyridine-3-carboxylic acidYield 92.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

2M aqueous sodium hydroxide solution (20 mL) was added to a solution of methyl 6-(1-((6-cyclopropyl-3-ethoxy-2,4′-difluorobiphenyl-4-yl)methyl)piperidin-4-yl)-2-ethyl-5-oxo-5,6,7,8-tetrahydro-1,6-naphthyridine-3-carboxylate (6.94 g) in methanol (20 mL) at room temperature. The mixture was stirred at 70° C. under nitrogen atmosphere for 2 hours. The mixture was neutralized with 1M hydrochloric acid at room temperature and stirred at 70° C. for 1 hour and at room temperature for 16 hours to give colorless crystals. After filtration, the crystals were dissolved in ethanol. The solution was filtrated and the filtrate was concentrated in vacuo to give a colorless solid. The solid was recrystallized from ethanol-DMSO-water (45 mL-5 mL-130 mL) to give the title compound (6.24 g).

Workup

  1. stirringstirred at 70° C. for 1 hour and at room temperature for 16 hours
  2. customto give colorless crystals
  3. filtrationAfter filtration
  4. dissolutionthe crystals were dissolved in ethanol
  5. filtrationThe solution was filtrated
  6. concentrationthe filtrate was concentrated in vacuo
  7. customto give a colorless solid
  8. customThe solid was recrystallized from ethanol-DMSO-water (45 mL-5 mL-130 mL)

Sources & evidence

ORD record
ord-4b47e7cb021c48148335fb674dc6c589
Source dataset
uspto-grants-2016_05
Patent number
US09353108B2

Reaction notes

Loading…