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

HRID 511078노트

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HRID 511078 반응식
[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]

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 6228Dimethylformamide용매2회HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-a68e05d0ff43430ba1587991630d36ab
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09096524B2

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