Triethylamine → Ethyl 6-(1-((6-cyclopropyl-3-ethoxy-2,4'-difluorobiphenyl-4-yl)methyl)piperidin-4-yl)-5-oxo-2-propyl-5,6,7,8-tetrahydro-1,6-naphthyridine-3-carboxylate

HRID 531092Notes

Reaction equation

HRID 531092 reaction equation
C(N(CC)CC)C.O.Cl.Cl.[O:11]=[C:12]1[N:21]([CH:22]2[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]2)[CH2:20][CH2:19][C:18]2[N:17]=[C:16]([CH2:28][CH2:29][CH3:30])[C:15]([C:31]([O:33][CH2:34][CH3:35])=[O:32])=[CH:14][C:13]1=2.[CH:36]1([C:39]2[C:44]([C:45]3[CH:50]=[CH:49][C:48]([F:51])=[CH:47][CH:46]=3)=[C:43]([F:52])[C:42]([O:53][CH2:54][CH3:55])=[C:41]([CH:56]=O)[CH:40]=2)[CH2:38][CH2:37]1.[Na]>C1COCC1>[CH:36]1([C:39]2[C:44]([C:45]3[CH:50]=[CH:49][C:48]([F:51])=[CH:47][CH:46]=3)=[C:43]([F:52])[C:42]([O:53][CH2:54][CH3:55])=[C:41]([CH2:56][N:25]3[CH2:24][CH2:23][CH:22]([N:21]4[CH2:20][CH2:19][C:18]5[N:17]=[C:16]([CH2:28][CH2:29][CH3:30])[C:15]([C:31]([O:33][CH2:34][CH3:35])=[O:32])=[CH:14][C:13]=5[C:12]4=[O:11])[CH2:27][CH2:26]3)[CH:40]=2)[CH2:38][CH2:37]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 5360545SodiumHCID 904235146-Cyclopropyl-3-ethoxy-2,4'-difluorobiphenyl-4-carbaldehydeHCID 131735653Ethyl 5-oxo-6-(piperidin-4-yl)-2-propyl-5,6,7,8-tetrahydro-1,6-naphthyridine-3-carboxylate dihydrochloride monohydrate

Product 1

HCID 117992314Ethyl 6-(1-((6-cyclopropyl-3-ethoxy-2,4'-difluorobiphenyl-4-yl)methyl)piperidin-4-yl)-5-oxo-2-propyl-5,6,7,8-tetrahydro-1,6-naphthyridine-3-carboxylateYield 93.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Triethylamine (3.26 g) was added to a mixture of ethyl 5-oxo-6-(piperidin-4-yl)-2-propyl-5,6,7,8-tetrahydro-1,6-naphthyridine-3-carboxylate dihydrochloride monohydrate (5.92 g) and 6-cyclopropyl-3-ethoxy-2,4′-difluorobiphenyl-4-carbaldehyde (5.35 g) in THF (100 mL) at room temperature. The mixture was stirred at the same temperature under nitrogen atmosphere for 10 minutes. Sodium triacetoxyhydroborate (6.82 g) was added to the reaction mixture at room temperature. The mixture was stirred at the same temperature under nitrogen atmosphere for 16 hours. The mixture was quenched with saturated sodium hydrogen carbonate aqueous solution at room temperature and extracted with ethyl acetate. The organic layer was separated, washed with water and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was purified by a silica gel column chromatography (hexane/ethyl acetate then NH silica gel, hexane/ethyl acetate) to give the title compound (7.98 g)

Workup

  1. stirringThe mixture was stirred at the same temperature under nitrogen atmosphere for 16 hours
  2. customThe mixture was quenched with saturated sodium hydrogen carbonate aqueous solution at room temperature
  3. extractionextracted with ethyl acetate
  4. customThe organic layer was separated
  5. washwashed with water and brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by a silica gel column chromatography (hexane/ethyl acetate

Sources & evidence

ORD record
ord-a34d36904515466a81a531ed91799cee
Source dataset
uspto-grants-2016_05
Patent number
US09353108B2

Reaction notes

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