Diisopropylethylamine → 4-[4-(4-tert-butyl-phenyl)-piperazin-1-yl]-1-[(R)-3-(4-nitro-3-trifluoromethyl-phenylamino)-pyrrolidin-1-yl]-butan-1-one

HRID 511204Notes

Reaction equation

HRID 511204 reaction equation
[Li+].[C:2]([C:6]1[CH:11]=[CH:10][C:9]([N:12]2[CH2:17][CH2:16][N:15]([CH2:18][CH2:19][CH2:20][C:21]([O-])=[O:22])[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.C(N(C(C)C)CC)(C)C.Cl.[N+:58]([C:61]1[CH:66]=[CH:65][C:64]([NH:67][C@@H:68]2[CH2:72][CH2:71][NH:70][CH2:69]2)=[CH:63][C:62]=1[C:73]([F:76])([F:75])[F:74])([O-:60])=[O:59].[O-2].[Al+3].[O-2].[O-2].[Al+3]>O1CCCC1.CN(C)C=O>[C:2]([C:6]1[CH:7]=[CH:8][C:9]([N:12]2[CH2:17][CH2:16][N:15]([CH2:18][CH2:19][CH2:20][C:21]([N:70]3[CH2:71][CH2:72][C@@H:68]([NH:67][C:64]4[CH:65]=[CH:66][C:61]([N+:58]([O-:60])=[O:59])=[C:62]([C:73]([F:74])([F:76])[F:75])[CH:63]=4)[CH2:69]3)=[O:22])[CH2:14][CH2:13]2)=[CH:10][CH:11]=1)([CH3:4])([CH3:5])[CH3:3]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 9989226AluminaHCID 585763684-[4-(4-Tert-butylphenyl)-piperazin-1-yl]-butyric acid lithium saltHCID 67995634(4-nitro-3-trifluoromethyl-phenyl)-(R)-pyrrolidin-3-yl-amine hydrochloride

Product 1

HCID 585770164-[4-(4-tert-butyl-phenyl)-piperazin-1-yl]-1-[(R)-3-(4-nitro-3-trifluoromethyl-phenylamino)-pyrrolidin-1-yl]-butan-1-oneYield 60%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To as suspension of 4-[4-(4-tert-butylphenyl)-piperazin-1-yl]-butyric acid lithium salt (15 mg; 0.05 mmol, prepared in accord with Example 167) in tetrahydrofuran (1 mL) is added a solution of tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate (19 mg; 0.05 mmol) in dimethylformamide (0.5 mL). After 15 minutes at room temperature, diisopropylethyl amine (25 μL; 0.15 mmol) and a solution of (4-nitro-3-trifluoromethyl-phenyl)-(R)-pyrrolidin-3-yl-amine hydrochloride (16 mg; 0.05 mmol, prepared in accord with Example 165) in dimethylformamide (0.5 mL) is added and the reaction mixture is stirred at room temperature for one hour. Aluminium oxide (90 active basic) is then added and stiffing is continued. 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 (17 mg; 0.030 mmol). The structure was confirmed using Protocol I-D. Calculated mass=562; observed mass=562; HPLC retention time=1.60 min.

Workup

  1. customThe solids are removed by filtration
  2. concentrationthe filtrate is concentrated under high vacuum
  3. customThe obtained residue is purified by preparative HPLC

Sources & evidence

ORD record
ord-b179ae3cbdc8478c9d04ab9f279c6148
Source dataset
uspto-grants-2015_08
Patent number
US09096524B2

Reaction notes

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