1-Hydroxybenzotriazole → Rac-1-acetyl-piperidine-4-carboxylic acid{2-[[6-chloro-3-(3-chloro-benzyl)-2-oxo-2,3-dihydro-1h-indol-3-yl]-(2,2-dimethyl-propyl)-amino]-ethyl}-amide

HRID 556499Notes

Reaction equation

HRID 556499 reaction equation
[NH2:1][CH2:2][CH2:3][N:4]([CH2:24][C:25]([CH3:28])([CH3:27])[CH3:26])[C:5]1([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[CH:18]=2)[C:13]2[C:8](=[CH:9][C:10]([Cl:14])=[CH:11][CH:12]=2)[NH:7][C:6]1=[O:15].[C:29]([N:32]1[CH2:37][CH2:36][CH:35]([C:38](O)=[O:39])[CH2:34][CH2:33]1)(=[O:31])[CH3:30].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>ClCCl>[Cl:14][C:10]1[CH:9]=[C:8]2[C:13]([C:5]([N:4]([CH2:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH2:3][CH2:2][NH:1][C:38]([CH:35]3[CH2:34][CH2:33][N:32]([C:29](=[O:31])[CH3:30])[CH2:37][CH2:36]3)=[O:39])([CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[CH:18]=3)[C:6](=[O:15])[NH:7]2)=[CH:12][CH:11]=1

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 1172551-Acetylpiperidine-4-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57507348HCID 57507348, compound

Product 1

HCID 59703577Rac-1-acetyl-piperidine-4-carboxylic acid{2-[[6-chloro-3-(3-chloro-benzyl)-2-oxo-2,3-dihydro-1h-indol-3-yl]-(2,2-dimethyl-propyl)-amino]-ethyl}-amideYield 32.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The mixture 3-[(2-Amino-ethyl)-(2,2-dimethyl-propyl)-amino]-6-chloro-3-(3-chloro-benzyl)-1,3-dihydro-indol-2-one (120 mg, 0.286 mmol), 1-Acetyl-piperidine-4-carboxylic acid (59 mg, 0.344 mmol), EDC.HCl (66 mg, 0.344 mmol), HOBt (46 mg, 0.344 mmol) and DIPEA (111 mg, 0.860 mmol) in dichloro-methane (2 mL) was stirred at room temperature for overnight. The crude was then purified with Prep-HPLC to give 54 mg rac-1-Acetyl-piperidine-4-carboxylic acid{2-[[6-chloro-3-(3-chloro-benzyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-(2,2-dimethyl-propyl)-amino]-ethyl}-amide of as a white solid. Then 18 mg rac-1-Acetyl-piperidine-4-carboxylic acid{2-[[6-chloro-3-(3-chloro-benzyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-(2,2-dimethyl-propyl)-amino]-ethyl}-amide was separated by chiral preparative HPLC to obtain 7 mg 1-Acetyl-piperidine-4-carboxylic acid{2-[[(S)-6-chloro-3-(3-chloro-benzyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-(2,2-dimethyl-propyl)-amino]-ethyl}-amide MS: [M+H]+=573.

Workup

  1. customThe crude was then purified with Prep-HPLC

Sources & evidence

ORD record
ord-ded95ea1418343f6a790402da565db7b
Source dataset
uspto-grants-2011_11
Patent number
US08058269B2

Reaction notes

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