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

HRID 511179
Notes
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Reaction equation

HRID 511179 reaction equation
[Li+].[F:2][C:3]([F:22])([F:21])[C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][CH:13]([CH2:16][CH2:17][C:18]([O-:20])=O)[CH2:12][CH2:11]2)=[CH:6][CH:5]=1.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>[N+:48]([C:51]1[CH:56]=[CH:55][C:54]([NH:57][CH:58]2[CH2:59][CH2:60][N:61]([C:18](=[O:20])[CH2:17][CH2:16][CH:13]3[CH2:12][CH2:11][N:10]([C:7]4[CH:6]=[CH:5][C:4]([C:3]([F:21])([F:2])[F:22])=[CH:9][CH:8]=4)[CH2:15][CH2:14]3)[CH2:62][CH2:63]2)=[CH:53][C:52]=1[C:64]([F:67])([F:65])[F:66])([O-:50])=[O:49]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 9989226AluminaHCID 585767453-[1-(4-Trifluoromethyl-phenyl)-piperidin-4-yl]-propionic acid lithium saltHCID 66671805(4-Nitro-3-trifluoromethyl-phenyl)-piperidin-4-yl-amine hydrochloride

Product

1
HCID 469465631-[4-(4-Nitro-3-trifluoromethyl-phenylamino)-piperidin-1-yl]-3-[1-(4-trifluoromethyl-phenyl)-piperidin-4-yl]-propan-1-oneYield 42%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-[1-(4-trifluoromethyl-phenyl)-piperidin-4-yl]-propionic acid lithium salt (15 mg; 0.05 mmol, prepared in accordance with Example 140) in tetrahydrofuran (1.0 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 stiffing 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 (12 mg; 0.021 mmol). The structure was confirmed using Protocol I-D. Calculated mass=572; observed mass=573; HPLC retention time=1.13 min.

Workup

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

Sources & evidence

ORD record
ord-da60e0b1fa074a6b99f6c7b75418276a
Source dataset
uspto-grants-2015_08
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09096524B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes