Diisopropylethylamine → 1-[4-(4-Nitro-3-trifluoromethyl-phenylamino)-piperidin-1-yl]-3-[4-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)-piperazin-1-yl]-propan-1-one

HRID 511164Notes

Reaction equation

HRID 511164 reaction equation
[Li+].[F:2][C:3]([F:21])([F:20])[C:4]1[S:8][C:7]([N:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][C:17]([O-:19])=O)[CH2:11][CH2:10]2)=[N:6][N:5]=1.F[P-](F)(F)(F)(F)F.CN(C)C(ON1C2C=CC=CC=2N=N1)=[N+](C)C.Cl.[N+:47]([C:50]1[CH:55]=[CH:54][C:53]([NH:56][CH:57]2[CH2:62][CH2:61][NH:60][CH2:59][CH2:58]2)=[CH:52][C:51]=1[C:63]([F:66])([F:65])[F:64])([O-:49])=[O:48].C(N(C(C)C)CC)(C)C.[O-2].[Al+3].[O-2].[O-2].[Al+3]>CN(C)C=O.O1CCCC1>[N+:47]([C:50]1[CH:55]=[CH:54][C:53]([NH:56][CH:57]2[CH2:58][CH2:59][N:60]([C:17](=[O:19])[CH2:16][CH2:15][N:12]3[CH2:11][CH2:10][N:9]([C:7]4[S:8][C:4]([C:3]([F:2])([F:21])[F:20])=[N:5][N:6]=4)[CH2:14][CH2:13]3)[CH2:61][CH2:62]2)=[CH:52][C:51]=1[C:63]([F:66])([F:64])[F:65])([O-:49])=[O:48]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 9989226AluminaHCID 58576587HCID 58576587, compoundHCID 66671805(4-Nitro-3-trifluoromethyl-phenyl)-piperidin-4-yl-amine hydrochloride

Product 1

HCID 585767001-[4-(4-Nitro-3-trifluoromethyl-phenylamino)-piperidin-1-yl]-3-[4-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)-piperazin-1-yl]-propan-1-oneYield 54%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

3-[4-(5-Trifluoromethyl-[1,3,4]thiadiazol-2-yl)-piperazin-1-yl]-propionic acid lithium salt (15 mg; 0.05 mmol, prepared in accordance with Example 123) and tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate (19 mg; 0.05 mmol) are diluted in a 2 to 1 mixture of dimethylformamide and tetrahydrofuran (0.75 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 added and the reaction is then stirred. After 4 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 (16 mg; 0.027 mmol). The structure was confirmed using Protocol I-D. Calculated mass=582; observed mass=582; HPLC retention time=1.41 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-cd263e21622541098ef41e4c1dae4ab3
Source dataset
uspto-grants-2015_08
Patent number
US09096524B2

Reaction notes

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