1-Hydroxybenzotriazole → HCID 66961126, Verbindung

HRID 1446523Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1446523
FC(F)(F)C(O)=O.[Cl:8][CH2:9][CH2:10][CH2:11]/[C:12](=[CH:16]\[C:17]1[CH:22]=[CH:21][C:20]([N:23]2[CH:27]=[C:26]([CH3:28])[N:25]=[CH:24]2)=[C:19]([O:29][CH3:30])[CH:18]=1)/[C:13]([OH:15])=O.[CH3:31][O:32][C:33]1[CH:41]=[C:40]2[C:36]([CH2:37][CH2:38][CH:39]2[NH2:42])=[CH:35][CH:34]=1.C(N(C(C)C)CC)(C)C.C1C=CC2N(O)N=NC=2C=1.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C.C(Cl)CCl.CN(C=O)C>[CH3:31][O:32][C:33]1[CH:41]=[C:40]2[C:36]([CH2:37][CH2:38][CH:39]2[NH:42][C:13](=[O:15])/[C:12](=[CH:16]/[C:17]2[CH:22]=[CH:21][C:20]([N:23]3[CH:27]=[C:26]([CH3:28])[N:25]=[CH:24]3)=[C:19]([O:29][CH3:30])[CH:18]=2)/[CH2:11][CH2:10][CH2:9][Cl:8])=[CH:35][CH:34]=1

Komponenten

9

Edukt 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 99204636-Methoxy-1-IndanamineHCID 66960186(E)-5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid trifluoroacetate

Produkt 1

HCID 66961126HCID 66961126, VerbindungAusbeute 54,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 111,2-DichloroethaneLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a DMF (2 mL) suspension of (E)-5-chloro-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene]valeric acid trifluoroacetic acid salt (50 mg) obtained in Example 418 and 6-methoxyindan-1-ylamine (CAS#103028-81-5) (27 mg), IPEA (0.06 mL), EDC (64 mg) and HOBT (45 mg) were added at room temperature, and the reaction solution was agitated at room temperature for 12 hours. Saturated sodium bicarbonate solution and ethyl acetate were added to the reaction solution, and the organic layer was partitioned. The organic layer was washed one by one with a saturated ammonium chloride solution and water, and also saturated sodium chloride solution, and the organic layer was concentrated under reduced pressure after dried over anhydrous magnesium sulfate. The obtained residue was purified by silica gel chromatography (elution solvent:methanol-ethyl acetate system) and (E)-5-chloro-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene]valeric acid (6-methoxyindan-1-yl)amide (29 mg) was obtained. To a DMF (2 mL) solution of (E)-5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid (6-methoxyindan-1-yl)amide (29 mg) obtained, sodium hydride (40% mineral oil content, 20 mg) was added at room temperature, and the reaction solution was agitated for 10 minutes at room temperature. Saturated sodium bicarbonate solution and ethyl acetate were added to the reaction solution, and the organic layer was partitioned. The organic layer was washed one by one in a saturated ammonium chloride solution and water, and also saturated sodium chloride solution, and the organic layer was concentrated under reduced pressure after dried over anhydrous magnesium sulfate. The obtained residue was purified by silica gel chromatography (elution solvent:methanol-ethyl acetate system), and (E)-1-(6-methoxyindan-1-yl)-3-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene]piperidin-2-one racemate (17 mg) was obtained. This compound (17 mg) was separated by CHIRALCEL™ AD-H available from Daicel Chemical Industries, Ltd. (2 cm×25 cm: mobile phase; ethanol), and the title optically-active substance with a retention time of 36 minutes (6 mg;>99% ee) and the title optically-active substance with a retention time of 43 minutes (6 mg;>95% ee) were obtained. The physical properties of the title optically-active substance with a retention time of 36 minutes (Example 421) is as follows.

Aufarbeitung

  1. additionwere added at room temperature
  2. customthe organic layer was partitioned
  3. washThe organic layer was washed one by one with a saturated ammonium chloride solution and water, and also saturated sodium chloride solution
  4. concentrationthe organic layer was concentrated under reduced pressure
  5. dry with materialafter dried over anhydrous magnesium sulfate
  6. customThe obtained residue was purified by silica gel chromatography (elution solvent:methanol-ethyl acetate system)

Quellen und Nachweise

ORD-Eintrag
ord-a3fd35fe0e7446b589721dd7b2381ea8
Quelldatensatz
uspto-grants-2010_02
Patentnummer
US07667041B2

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