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

HRID 531105Notes

Reaction equation

HRID 531105 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][CH:21]([CH3:23])[CH3:22])=[C:8]([CH2:24][N:25]3[CH2:30][CH2:29][CH:28]([N:31]4[CH2:40][CH2:39][C:38]5[N:37]=[C:36]([CH2:41][CH3:42])[C:35]([C:43]([O:45]C)=[O:44])=[CH:34][C:33]=5[C:32]4=[O:47])[CH2:27][CH2:26]3)[CH:7]=2)[CH2:5][CH2:4]1.Cl.O>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][CH:21]([CH3:23])[CH3:22])=[C:8]([CH2:24][N:25]3[CH2:26][CH2:27][CH:28]([N:31]4[CH2:40][CH2:39][C:38]5[N:37]=[C:36]([CH2:41][CH3:42])[C:35]([C:43]([OH:45])=[O:44])=[CH:34][C:33]=5[C:32]4=[O:47])[CH2:29][CH2:30]3)[CH:7]=2)[CH2:5][CH2:4]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 14798Sodium HydroxideHCID 117992462Methyl 6-(1-((6-cyclopropyl-2,4'-difluoro-3-isopropoxybiphenyl-4-yl)methyl)piperidin-4-yl)-2-ethyl-5-oxo-5,6,7,8-tetrahydro-1,6-naphthyridine-3-carboxylate

Product 1

HCID 1179921756-(1-((6-Cyclopropyl-2,4'-difluoro-3-isopropoxybiphenyl-4-yl)methyl)piperidin-4-yl)-2-ethyl-5-oxo-5,6,7,8-tetrahydro-1,6-naphthyridine-3-carboxylic acidYield 92.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

2M aqueous sodium hydroxide solution (20 mL) was added to a solution of methyl 6-(1-((6-cyclopropyl-2,4′-difluoro-3-isopropoxybiphenyl-4-yl)methyl)piperidin-4-yl)-2-ethyl-5-oxo-5,6,7,8-tetrahydro-1,6-naphthyridine-3-carboxylate (8.03 g) in methanol (25 mL) at 70° C. The mixture was stirred at the same temperature under nitrogen atmosphere for 2 hours. The mixture was neutralized with 1M hydrochloric acid at room temperature and added to water (100 mL). The mixture was stirred at 70° C. for 30 minutes and at room temperature for 2 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-water (45 mL-130 mL) to give the title compound (7.26 g).

Workup

  1. stirringThe mixture was stirred at 70° C. for 30 minutes and at room temperature for 2 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-water (45 mL-130 mL)

Sources & evidence

ORD record
ord-f99b825a2ae24163a3b05c10f5c587ec
Source dataset
uspto-grants-2016_05
Patent number
US09353108B2

Reaction notes

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