Sodium Bicarbonate → Ethyl 6-(1-((2-cyclopropyl-5-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 531148Notes

Reaction equation

HRID 531148 reaction equation
O.Cl.Cl.[O:4]=[C:5]1[N:14]([CH:15]2[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]2)[CH2:13][CH2:12][C:11]2[N:10]=[C:9]([CH2:21][CH2:22][CH3:23])[C:8]([C:24]([O:26][CH2:27][CH3:28])=[O:25])=[CH:7][C:6]1=2.[CH:29]1([C:32]2[CH:37]=[C:36]([CH:38]=O)[C:35]([O:40][CH2:41][CH3:42])=[CH:34][C:33]=2[C:43]2[CH:48]=[CH:47][C:46]([F:49])=[CH:45][C:44]=2[F:50])[CH2:31][CH2:30]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>C1COCC1.O.C(O)(=O)C.C(N(CC)CC)C>[CH:29]1([C:32]2[CH:37]=[C:36]([CH2:38][N:18]3[CH2:17][CH2:16][CH:15]([N:14]4[CH2:13][CH2:12][C:11]5[N:10]=[C:9]([CH2:21][CH2:22][CH3:23])[C:8]([C:24]([O:26][CH2:27][CH3:28])=[O:25])=[CH:7][C:6]=5[C:5]4=[O:4])[CH2:20][CH2:19]3)[C:35]([O:40][CH2:41][CH3:42])=[CH:34][C:33]=2[C:43]2[CH:48]=[CH:47][C:46]([F:49])=[CH:45][C:44]=2[F:50])[CH2:31][CH2:30]1

Participants

9

Reactant 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 1179923862-Cyclopropyl-5-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 117992191Ethyl 6-(1-((2-cyclopropyl-5-ethoxy-2',4'-difluorobiphenyl-4-yl)methyl)piperidin-4-yl)-5-oxo-2-propyl-5,6,7,8-tetrahydro-1,6-naphthyridine-3-carboxylateYield 91%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

To a suspension of Ethyl 5-oxo-6-(piperidin-4-yl)-2-propyl-5,6,7,8-tetrahydro-1,6-naphthyridine-3-carboxylate dihydrochloride monohydrate (10.1 g) in THF (203 mL) was added triethylamine (6.49 mL). The mixture was stirred for 30 minutes. 2-Cyclopropyl-5-ethoxy-2′,4′-difluorobiphenyl-4-carbaldehyde (7.73 g) was added to the mixture. The mixture was stirred for 30 minutes. Then Sodium triacetoxyborohydride (7.39 g) and acetic acid (1.33 mL) was added to the reaction mixture. The mixture was stirred at room temperature for overnight. The mixture was added to aqueous saturated sodium hydrogen carbonate solution (135 mL) and water (135 mL) at room temperature. The mixture was extracted with ethyl acetate (1.35 L). The organic layer was separated, washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by a silica gel column chromatography (hexane/ethyl acetate) to give the title compound (13.3 g).

Workup

  1. stirringThe mixture was stirred for 30 minutes
  2. stirringThe mixture was stirred at room temperature for overnight
  3. extractionThe mixture was extracted with ethyl acetate (1.35 L)
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by a silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-fc70b65ebc5b45cc980d63cd31557f49
Source dataset
uspto-grants-2016_05
Patent number
US09353108B2

Reaction notes

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