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

HRID 511182Notes

Reaction equation

HRID 511182 reaction equation
[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

Participants

8

Reactant 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

Product 1

HCID 585767213-[1-(4-Chloro-phenyl)-piperidin-4-yl]-1-[4-(4-nitro-3-trifluoromethyl-phenylamino)-piperidin-1-yl]-propan-1-oneYield 24%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-29851b90623542dbac0442e9a96b51ac
Source dataset
uspto-grants-2015_08
Patent number
US09096524B2

Reaction notes

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