Diisopropylethylamine → N-benzyl-1-(1-(4-chlorobenzyl)-3-methyl-1H-indole-2-carbonyl)piperidine-4-carboxamide

HRID 83684

Reaction equation

HRID 83684 reaction equation
[Cl:1][C:2]1[CH:21]=[CH:20][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]([CH3:16])=[C:8]2[C:17]([OH:19])=O)=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:55]([NH:62][C:63]([CH:65]1[CH2:70][CH2:69][NH:68][CH2:67][CH2:66]1)=[O:64])[C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1>CCOC(C)=O.CN(C=O)C>[CH2:55]([NH:62][C:63]([CH:65]1[CH2:70][CH2:69][N:68]([C:17]([C:8]2[N:7]([CH2:6][C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:21][CH:20]=3)[C:15]3[C:10]([C:9]=2[CH3:16])=[CH:11][CH:12]=[CH:13][CH:14]=3)=[O:19])[CH2:67][CH2:66]1)=[O:64])[C:56]1[CH:57]=[CH:58][CH:59]=[CH:60][CH:61]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 3868064N-benzylpiperidine-4-carboxamideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 683797421-(4-chlorobenzyl)-3-methyl-1H-indole-2-carboxylic acid

Product 1

HCID 66571685N-benzyl-1-(1-(4-chlorobenzyl)-3-methyl-1H-indole-2-carbonyl)piperidine-4-carboxamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

The following was added to sequentially to DMF (3 mL): 1-(4-chlorobenzyl)-3-methyl-1H-indole-2-carboxylic acid (90 mg, 0.315 mmol), DIPEA (0.170 mL, 0.945 mmol), and HATU (144 mg, 0.378 mmol). This was allowed to stir for 30 min at rt, after which time the crude N-benzylpiperidine-4-carboxamide (˜70 mg, 0.315 mmol) was added. The reaction was stirred at rt for 17 h, at which time the reaction was diluted with 1:1 EtOAc:diethyl ether and washed with 10% aq. sodium carbonate (2×), dried over magnesium sulfate, and concentrated. The residue was purified via silica gel flash chromatography (20 g silica, 50% EtOAc/Hexanes) to afford the title compound as an oil. Yield: (77 mg, 0.153 mmol, 51%) 1H NMR (400 MHz, CDCl3) 7.59, 7.34-7.14, 7.03, 5.73, 5.57, 5.43-5.32, 4.76, 4.43, 3.77-3.64, 3.10, 2.80, 2.19-1.52

Workup

  1. stirringThe reaction was stirred at rt for 17 h, at which time the reaction
  2. washdiethyl ether and washed with 10% aq. sodium carbonate (2×)
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified via silica gel flash chromatography (20 g silica, 50% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-3d24471df73c4188ab81f0d26204cecc
Source dataset
uspto-grants-2014_09
Patent number
US08846684B2

Linked notes

Loading…