Triethylamine → (4R)-N-[(1R,3S)-3-(Ethoxymethyl)-3-(4-[4-(trifluoromethyl)pyridin-2-yl]piperazin-1-ylcarbonyl)cyclopentyl]-3-methyltetrahydro-2H-pyran-4-amine

HRID 270612Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 270612
Cl.Cl.[CH2:3]([O:5][CH2:6][C@:7]1([C:13]([N:15]2[CH2:20][CH2:19][N:18]([C:21]3[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[CH:23][N:22]=3)[CH2:17][CH2:16]2)=[O:14])[CH2:11][CH2:10][C@@H:9]([NH2:12])[CH2:8]1)[CH3:4].[CH3:31][CH:32]1[C:37](=O)[CH2:36][CH2:35][O:34][CH2:33]1.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[CH2:3]([O:5][CH2:6][C@:7]1([C:13]([N:15]2[CH2:16][CH2:17][N:18]([C:21]3[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[CH:23][N:22]=3)[CH2:19][CH2:20]2)=[O:14])[CH2:11][CH2:10][C@@H:9]([NH:12][C@@H:37]2[CH2:36][CH2:35][O:34][CH2:33][CH:32]2[CH3:31])[CH2:8]1)[CH3:4]

Komponenten

6

Edukt 4

HCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 141709263-Methyloxan-4-oneHCID 68596125(1R,3S)-3-(Ethoxymethyl)-3-(4-[4-(trifluoromethyl)pyridin-2-yl]piperazin-1-ylcarbonyl)cyclopentanamine Dihydrochloride

Produkt 1

HCID 68596221(4R)-N-[(1R,3S)-3-(Ethoxymethyl)-3-(4-[4-(trifluoromethyl)pyridin-2-yl]piperazin-1-ylcarbonyl)cyclopentyl]-3-methyltetrahydro-2H-pyran-4-amineAusbeute 34 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of (1R,3S)-3-(ethoxymethyl)-3-(4-[4-(trifluoromethyl)pyridin-2-yl]piperazin-1-ylcarbonyl)cyclopentanamine dihydrochloride (100.0 mg, 0.211 mmol), 3-methyltetrahydro-4H-pyran-4-one (72.3 mg, 0.634 mmol) and triethylamine (0.118 mL, 0.845 mmol) in dry methylene chloride (5 mL) was added sodium triacetoxyborohydride (134.3 mg, 0.634 mmol). After being stirred at room temperature under N2 overnight, the reaction was quenched with aqueous NaHCO3 and diluted with methylene chloride. The organic layer was separated and the aqueous layer was extracted with methylene chloride three times. The organics were combined, dried over MgSO4, filtered, purified by silica gel Combi-Flash system (gradient, 0 to 40% MeOH in EtOAc, 12 gram column) to give the desired product (34 mg, 34%). MS calculated for C25H37F3N4O3: (M+H) 499.3; found 499.3.

Aufarbeitung

  1. customthe reaction was quenched with aqueous NaHCO3
  2. additiondiluted with methylene chloride
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with methylene chloride three times
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. custompurified by silica gel Combi-Flash system (gradient, 0 to 40% MeOH in EtOAc, 12 gram column)

Quellen und Nachweise

ORD-Eintrag
ord-5df494de94ad4d68bbc5554788e20e6d
Quelldatensatz
uspto-grants-2008_11
Patentnummer
US07449467B2

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