Diisopropylethylamine → 1-[4-(4-Chloro-3-trifluoromethylsulfanyl-phenylamino)-piperidin-1-yl]-4-[4-(4-trifluoromethyl-phenyl)-piperazin-1-yl]-butan-1-one

HRID 511078ノート

反応式

HRID 511078 の反応式
[Li+].[F:2][C:3]([F:23])([F:22])[C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][CH2:18][C:19]([O-])=[O:20])[CH2:12][CH2:11]2)=[CH:6][CH:5]=1.C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.CN(C)C(ON1C2C=CC=CC=2N=N1)=[N+](C)C.Cl.[Cl:58][C:59]1[CH:64]=[CH:63][C:62]([NH:65][CH:66]2[CH2:71][CH2:70][NH:69][CH2:68][CH2:67]2)=[CH:61][C:60]=1[S:72][C:73]([F:76])([F:75])[F:74]>CN(C)C=O.ClCCl.O1CCCC1>[Cl:58][C:59]1[CH:64]=[CH:63][C:62]([NH:65][CH:66]2[CH2:71][CH2:70][N:69]([C:19](=[O:20])[CH2:18][CH2:17][CH2:16][N:13]3[CH2:14][CH2:15][N:10]([C:7]4[CH:8]=[CH:9][C:4]([C:3]([F:2])([F:22])[F:23])=[CH:5][CH:6]=4)[CH2:11][CH2:12]3)[CH2:68][CH2:67]2)=[CH:61][C:60]=1[S:72][C:73]([F:76])([F:74])[F:75]

参加物

8

反応物 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 585760704-[4-(4-Trifluoromethyl-phenyl)-piperazin-1-yl]-butyric acid lithium saltHCID 66671939(4-Chloro-3-trifluoromethylsulfanyl-phenyl)-piperidin-4-yl-amine hydrochloride

生成物 1

HCID 469465641-[4-(4-Chloro-3-trifluoromethylsulfanyl-phenylamino)-piperidin-1-yl]-4-[4-(4-trifluoromethyl-phenyl)-piperazin-1-yl]-butan-1-one

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒2 回HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

4-[4-(4-Trifluoromethyl-phenyl)-piperazin-1-yl]-butyric acid lithium salt (16 mg; 0.05 mmol, prepared in accordance with Example 3), diisopropylethyl amine (18 μL; 0.10 mmol) and tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate (19 mg; 0.05 mmol) are diluted in a 2 to 1 mixture of dimethylformamide and tetrahydrofuran (1.5 mL) and the resulting solution is stirred for 5 minutes. A solution of (4-chloro-3-trifluoromethylsulfanyl-phenyl)-piperidin-4-yl-amine hydrochloride (17 mg; 0.05 mmol, prepared in accordance with Example 16) in dimethylformamide (0.5 mL) is added and the reaction is then stirred for 90 minutes at room temperature. Following dilution with dichloromethane (10 mL), the organic layer is sequentially washed with water (5 mL), aq. sat. sodium hydrogen carbonate (5 mL), is dried over magnesium sulfate and concentrated under reduced pressure. The residue obtained is finally purified by preparative HPLC to deliver the desired product in pure form (5 mg; 0.01 mmol). The structure was confirmed using Protocol I-B. Calculated mass=609; observed mass=609; HPLC retention time=4.89 min.

後処理

  1. stirringthe reaction is then stirred for 90 minutes at room temperature
  2. washthe organic layer is sequentially washed with water (5 mL), aq. sat. sodium hydrogen carbonate (5 mL)
  3. dry with materialis dried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue obtained
  6. customis finally purified by preparative HPLC

出典と根拠

ORDレコード
ord-a68e05d0ff43430ba1587991630d36ab
出典データセット
uspto-grants-2015_08
特許番号
US09096524B2

反応ノート

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