1-Hydroxybenzotriazole → (E)-5-chloro-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene]valeric acid [1-(2,4-difluorophenyl)ethyl]amide

HRID 1362701

反応式

HRID 1362701 の反応式
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.[F:31][C:32]1[CH:37]=[C:36]([F:38])[CH:35]=[CH:34][C:33]=1[CH:39]([NH2:41])[CH3:40].C(N(C(C)C)CC)(C)C.C1C=CC2N(O)N=NC=2C=1>C(OCC)(=O)C.O.C(Cl)CCl.CN(C=O)C>[F:31][C:32]1[CH:37]=[C:36]([F:38])[CH:35]=[CH:34][C:33]=1[CH:39]([NH:41][C:13](=[O:15])/[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)/[CH2:11][CH2:10][CH2:9][Cl:8])[CH3:40]

参加物

9

反応物 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 49862501-(2,4-Difluorophenyl)ethanamineHCID 66960186(E)-5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid trifluoroacetate

生成物 1

HCID 66961231(E)-5-chloro-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene]valeric acid [1-(2,4-difluorophenyl)ethyl]amide

試薬・触媒・溶媒 4

HCID 111,2-Dichloroethane溶媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a DMF (5 mL) solution of (E)-5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid trifluoroacetic acid salt (250 mg) obtained in Example 418 and 1-(2,4-difluorophenyl)ethylamine (CAS#603951-43-5, 141 mg), IPEA (0.5 mL), EDC (430 mg) and HOBT (303 mg) were added one by one, and the reaction solution was agitated at room temperature for 1 hour. Water and ethyl acetate were added to the reaction solution, and the organic layer was partitioned. The obtained organic layer was dried with anhydrous magnesium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (elution solvent: heptane-ethyl acetate system). (E)-5-chloro-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene]valeric acid [1-(2,4-difluorophenyl)ethyl]amide was obtained. Sodium hydride (40% mineral oil content, 20 mg) was added to a DMF (5 mL) solution of this compound, and that reaction solution was agitated at room temperature for 5 minutes. Water and ethyl acetate were added to the reaction solution, and the organic layer was partitioned. The obtained organic layer was dried with anhydrous magnesium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel chromatography (elution solvent: heptane-ethyl acetate system) 151 mg of (E)-1-(1-(2,4-difluorophenyl)ethyl)-3-(3-methoxy-4-(methyl-1H-imidazol-1-yl)benzylidene)piperidin-2-one racemate was obtained. This compound (25 mg) was separated in CHIRALPAK™ AD-H available from Daicel Chemical Industries, Ltd. (2 cm×25 cm: mobile phase; hexane:ethanol=7:3), and the title optically active substance with a retention time of 25 minutes (Example 620: 11.8 mg; >99% ee) and the title optically active substance with a retention time of 45 minutes (Example 621: 11.2 mg; >99% ee) were obtained. The physical properties of the title optically active compound with a retention time of 25 minutes are as follows.

後処理

  1. customthe organic layer was partitioned
  2. dry with materialThe obtained organic layer was dried with anhydrous magnesium sulfate
  3. customthe solvent was evaporated under reduced pressure
  4. customthe residue was purified by silica gel column chromatography (elution solvent: heptane-ethyl acetate system)

出典と根拠

ORDレコード
ord-36380c338ef44cdc8bd1392db91e4bac
出典データセット
uspto-grants-2011_02
特許番号
US07880009B2

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