1,2-Dichloroethane → 1-(1-(4-chlorobenzyl)-1H-indole-2-carbonyl)-N-((2,3-dihydro-1H-inden-1-yl)methyl)piperidine-4-carboxamide

HRID 83676Notes

Reaction equation

HRID 83676 reaction equation
[Cl:1][C:2]1[CH:28]=[CH:27][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH:9]=[C:8]2[C:16]([N:18]2[CH2:23][CH2:22][CH:21]([C:24](O)=[O:25])[CH2:20][CH2:19]2)=[O:17])=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.C(Cl)CCl.[CH:42]1[CH:43]=[CH:44][C:45]2N(O)N=N[C:46]=2[CH:47]=1.Cl.[CH2:53]1[C:61]2C(=CC=CC=2)C[CH:54]1[CH2:62][NH2:63]>C(OCC)(=O)C.C(Cl)Cl>[Cl:1][C:2]1[CH:28]=[CH:27][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH:9]=[C:8]2[C:16]([N:18]2[CH2:23][CH2:22][CH:21]([C:24]([NH:63][CH2:62][CH:54]3[C:45]4[C:46](=[CH:47][CH:42]=[CH:43][CH:44]=4)[CH2:61][CH2:53]3)=[O:25])[CH2:20][CH2:19]2)=[O:17])=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 54594123INDAN-2-YL-METHYLAMINE HYDROCHLORIDEHCID 573857961-(1-(4-chlorobenzyl)-1H-indole-2-carbonyl)piperidine-4-carboxylic acid

Product 1

HCID 665716821-(1-(4-chlorobenzyl)-1H-indole-2-carbonyl)-N-((2,3-dihydro-1H-inden-1-yl)methyl)piperidine-4-carboxamide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

The following was added sequentially to DCM (6 mL): 1-(1-(4-chlorobenzyl)-1H-indole-2-carbonyl)piperidine-4-carboxylic acid (134 mg, 0.340 mmol), DIPEA (0.178 mL, 1.019 mmol), EDC (78 mg, 0.408 mmol), HOBT (62.4 mg, 0.408 mmol), and 2-indanmethanamine hydrochloride (62 mg, 0.340 mmol). The mixture was stirred for 18 h at rt, at which time the solution diluted with a 1:1 solution of ethyl acetate:diethyl ether and washed with 1M HCl (1×), 10% aq. sodium carbonate (1×) and brine (1×). The organic phase was dried with magnesium sulfate and concentrated in vacuo. The resulting residue was dissolved in EtOAc and precipitated out hexanes, and then collected over a filter and washed with diethyl ether to give the title compound as a white solid. (Yield: 72 mg, 0.137 mmol, 41%) 1H NMR (400 MHz, CDCl3) 7.63, 7.32, 7.28-7.11, 7.01, 6.62, 5.45, 5.38, 4.36, 3.70-3.52, 3.51-3.07, 3.06-2.76, 2.30-2.19, 1.86-1.61, 1.49

Workup

  1. washdiethyl ether and washed with 1M HCl (1×), 10% aq. sodium carbonate (1×) and brine (1×)
  2. dry with materialThe organic phase was dried with magnesium sulfate
  3. concentrationconcentrated in vacuo
  4. dissolutionThe resulting residue was dissolved in EtOAc
  5. customprecipitated out hexanes
  6. customcollected over
  7. filtrationa filter
  8. washwashed with diethyl ether

Sources & evidence

ORD record
ord-33db8dd020784bb8ad8beb42fdd38a83
Source dataset
uspto-grants-2014_09
Patent number
US08846684B2

Reaction notes

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