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Diisopropylethylamine → 3-[1-(4-Chloro-phenyl)-piperidin-4-yl]-1-[4-(4-nitro-3-trifluoromethyl-phenylamino)-piperidin-1-yl]-propan-1-one

HRID 511182
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HRID 511182 반응식
[Li+].[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][CH:12]([CH2:15][CH2:16][C:17]([O-:19])=O)[CH2:11][CH2:10]2)=[CH:5][CH:4]=1.F[P-](F)(F)(F)(F)F.CN(C)C(ON1C2C=CC=CC=2N=N1)=[N+](C)C.Cl.[N+:45]([C:48]1[CH:53]=[CH:52][C:51]([NH:54][CH:55]2[CH2:60][CH2:59][NH:58][CH2:57][CH2:56]2)=[CH:50][C:49]=1[C:61]([F:64])([F:63])[F:62])([O-:47])=[O:46].C(N(C(C)C)CC)(C)C.[O-2].[Al+3].[O-2].[O-2].[Al+3]>O1CCCC1.CN(C)C=O>[Cl:2][C:3]1[CH:4]=[CH:5][C:6]([N:9]2[CH2:10][CH2:11][CH:12]([CH2:15][CH2:16][C:17]([N:58]3[CH2:59][CH2:60][CH:55]([NH:54][C:51]4[CH:52]=[CH:53][C:48]([N+:45]([O-:47])=[O:46])=[C:49]([C:61]([F:62])([F:63])[F:64])[CH:50]=4)[CH2:56][CH2:57]3)=[O:19])[CH2:13][CH2:14]2)=[CH:7][CH:8]=1
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참가 물질

8

반응물 5

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 9989226AluminaHCID 585764893-[1-(4-Chloro-phenyl)-piperidin-4-yl]-propionic acid lithium saltHCID 66671805(4-Nitro-3-trifluoromethyl-phenyl)-piperidin-4-yl-amine hydrochloride

생성물 1

HCID 58576721
3-[1-(4-Chloro-phenyl)-piperidin-4-yl]-1-[4-(4-nitro-3-trifluoromethyl-phenylamino)-piperidin-1-yl]-propan-1-one
수율 24%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매2회HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of 3-[1-(4-chloro-phenyl)-piperidin-4-yl]-propionic acid lithium salt (14 mg; 0.05 mmol, prepared in accordance with Example 143) in tetrahydrofuran (0.5 mL) is added tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate (19 mg; 0.05 mmol) in dimethylformamide (0.25 mL). A solution of (4-nitro-3-trifluoromethyl-phenyl)-piperidin-4-yl-amine hydrochloride (16 mg; 0.05 mmol, prepared in accordance with Example 8) in dimethylformamide (0.25 mL) and diisopropylethyl amine (25 μL; 0.15 mmol) are then added and the reaction is stirred. After 3 hours at room temperature, aluminium oxide (90 active basic) is added and stirring is continued for 40 minutes. The solids are removed by filtration and the filtrate is concentrated under high vacuum. The obtained residue is purified by preparative HPLC to afford the desired compound (6 mg; 0.012 mmol). The structure was confirmed using Protocol I-D. Calculated mass=539; observed mass=539; HPLC retention time=1.88 min.

후처리

  1. stirringstirring
  2. waitis continued for 40 minutes
  3. customThe solids are removed by filtration
  4. concentrationthe filtrate is concentrated under high vacuum
  5. customThe obtained residue is purified by preparative HPLC

출처 및 근거

ORD 기록
ord-29851b90623542dbac0442e9a96b51ac
출처 데이터셋
uspto-grants-2015_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09096524B2

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