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 531148Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 531148
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

Komponenten

9

Edukt 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

Produkt 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-carboxylateAusbeute 91 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 176Acetic AcidLösungsmittelHCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 8471TriethylamineLösungsmittel

Versuchsvorschrift

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).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-fc70b65ebc5b45cc980d63cd31557f49
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09353108B2

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