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

HRID 511185ノート

反応式

HRID 511185 の反応式
[Li+].[C:2]([C:6]1[CH:11]=[CH:10][C:9]([N:12]2[CH2:17][CH2:16][CH:15]([CH2:18][CH2:19][C:20]([O-])=[O:21])[CH2:14][CH2:13]2)=[CH:8][CH:7]=1)([CH3:5])([CH3:4])[CH3:3].F[P-](F)(F)(F)(F)F.CN(C)C(ON1C2C=CC=CC=2N=N1)=[N+](C)C.Cl.[N+:48]([C:51]1[CH:56]=[CH:55][C:54]([NH:57][CH:58]2[CH2:63][CH2:62][NH:61][CH2:60][CH2:59]2)=[CH:53][C:52]=1[C:64]([F:67])([F:66])[F:65])([O-:50])=[O:49].C(N(C(C)C)CC)(C)C.[O-2].[Al+3].[O-2].[O-2].[Al+3]>O1CCCC1.CN(C)C=O>[C:2]([C:6]1[CH:11]=[CH:10][C:9]([N:12]2[CH2:13][CH2:14][CH:15]([CH2:18][CH2:19][C:20]([N:61]3[CH2:60][CH2:59][CH:58]([NH:57][C:54]4[CH:55]=[CH:56][C:51]([N+:48]([O-:50])=[O:49])=[C:52]([C:64]([F:67])([F:65])[F:66])[CH:53]=4)[CH2:63][CH2:62]3)=[O:21])[CH2:16][CH2:17]2)=[CH:8][CH:7]=1)([CH3:5])([CH3:3])[CH3:4]

参加物

8

反応物 5

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 9989226AluminaHCID 585759763-[1-(4-Tert-butyl-phenyl)-piperidin-4-yl]-propionic acid lithium saltHCID 66671805(4-Nitro-3-trifluoromethyl-phenyl)-piperidin-4-yl-amine hydrochloride

生成物 1

HCID 585760873-[1-(4-Tert-butyl-phenyl)-piperidin-4-yl]-1-[4-(4-nitro-3-trifluoromethyl-phenylamino)-piperidin-1-yl]-propan-1-one収率 22%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒2 回HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of 3-[1-(4-tert-butyl-phenyl)-piperidin-4-yl]-propionic acid lithium salt (15 mg; 0.05 mmol, prepared in accordance with Example 146) 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; 0.011 mmol). The structure was confirmed using Protocol I-D. Calculated mass=561; observed mass=561; HPLC retention time=1.67 min.

後処理

  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

出典と根拠

ORDレコード
ord-75e5be9f10984dd280c0c1bf9ba458d6
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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