Diisopropylethylamine → 1-(3,3-Dimethyl-butyl)-piperidine-4-carboxylic Acid 4-[(4-chloro-phenyl)-methyl-carbamoyl]-2-methyl-benzylamide

HRID 220977Notes

Reaction equation

HRID 220977 reaction equation
CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:25][C:26]([CH3:39])([CH3:38])[CH2:27][CH2:28][N:29]1[CH2:34][CH2:33][CH:32]([C:35]([OH:37])=O)[CH2:31][CH2:30]1.CCN(C(C)C)C(C)C.[NH2:49][CH2:50][C:51]1[CH:67]=[CH:66][C:54]([C:55]([N:57]([C:59]2[CH:64]=[CH:63][C:62]([Cl:65])=[CH:61][CH:60]=2)[CH3:58])=[O:56])=[CH:53][C:52]=1[CH3:68]>CN(C=O)C.CCOC(C)=O>[Cl:65][C:62]1[CH:63]=[CH:64][C:59]([N:57]([CH3:58])[C:55]([C:54]2[CH:66]=[CH:67][C:51]([CH2:50][NH:49][C:35]([CH:32]3[CH2:31][CH2:30][N:29]([CH2:28][CH2:27][C:26]([CH3:25])([CH3:39])[CH3:38])[CH2:34][CH2:33]3)=[O:37])=[C:52]([CH3:68])[CH:53]=2)=[O:56])=[CH:60][CH:61]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 231123781-(3,3-Dimethylbutyl)piperidine-4-carboxylic acidHCID 575552204-Aminomethyl-N-(4-chloro-phenyl)-3,N-dimethyl-benzamide

Product 1

HCID 575554281-(3,3-Dimethyl-butyl)-piperidine-4-carboxylic Acid 4-[(4-chloro-phenyl)-methyl-carbamoyl]-2-methyl-benzylamideYield 83%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

HBTU (296 mg, 0.78 mmol) was added to a solution of 1-(3,3-dimethyl-butyl)-piperidine-4-carboxylic acid from Example E15 (182 mg, 0.73 mmol) in DMF (5 ml) and DIEA (0.272 ml, 1.56 mmol). The mixture was stirred at room temperature for 2 h then 4-aminomethyl-N-(4-chloro-phenyl)-3,N-dimethyl-benzamide from Example E115.2 (150 mg, 0.52 mmol) was added. The mixture was stirred for 2 h at room temperature then diluted with EtOAc, washed with saturated NaHCO3 then brine, dried and concentrated in vacuo. The residue was purified by preparative HPLC (eluant; 0.5% 35% ammonia:9.5% methanol:90% dichloromethane) to give a white powder identified as the title compound (209 mg, 83%).

Workup

  1. stirringThe mixture was stirred for 2 h at room temperature
  2. washwashed with saturated NaHCO3
  3. dry with materialbrine, dried
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by preparative HPLC (eluant; 0.5% 35% ammonia:9.5% methanol:90% dichloromethane)
  6. customto give a white powder

Sources & evidence

ORD record
ord-6bc183089b3143d18b804a2044101a58
Source dataset
uspto-grants-2012_06
Patent number
US08202858B2

Reaction notes

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