Piperidine → 2-{4-[(E)-3-(3,4-dichloro-phenyl)-acryloyl]-7-oxo-[1,4]diazepan-1-yl}-4-oxo-4-piperidin-1-yl-butyric acid methyl ester

HRID 2095536Notes

Reaction equation

HRID 2095536 reaction equation
[CH3:1][O:2][C:3](=[O:29])[CH:4]([N:9]1[C:15](=[O:16])[CH2:14][CH2:13][N:12]([C:17](=[O:28])/[CH:18]=[CH:19]/[C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([Cl:27])[CH:21]=2)[CH2:11][CH2:10]1)[CH2:5][C:6](O)=[O:7].[NH:30]1[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.OS([O-])(=O)=O.[K+]>ClCCl>[CH3:1][O:2][C:3](=[O:29])[CH:4]([N:9]1[C:15](=[O:16])[CH2:14][CH2:13][N:12]([C:17](=[O:28])/[CH:18]=[CH:19]/[C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([Cl:27])[CH:21]=2)[CH2:11][CH2:10]1)[CH2:5][C:6](=[O:7])[N:30]1[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1

Participants

7

Reactant 5

HCID 8082PiperidineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 516920Potassium bisulfateHCID 670740782-{4-[(E)-3-(3,4-Dichloro-phenyl)-acryloyl]-7-oxo-[1,4]diazepan-1-yl}-succinic acid 1-methyl ester2×

Product 1

HCID 670740682-{4-[(E)-3-(3,4-dichloro-phenyl)-acryloyl]-7-oxo-[1,4]diazepan-1-yl}-4-oxo-4-piperidin-1-yl-butyric acid methyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 0.286 g (0.65 mmol) of 2-{4-[(E)-3-(3,4-dichloro-phenyl)-acryloyl]-7-oxo-[1,4]diazepan-1-yl}-succinic acid 1-methyl ester (intermediate 7) in 15 ml of dichloromethane was treated with 0.070 ml (0.71 mmol) of piperidine and at 0° C. with 0.148 g (0.77 mmol) of EDCI and 0.009 g (0.06 mmol) of HOBT. Over night, the suspension was naturally warmed to RT, poured on aqueous 10% KHSO4 solution and extracted with EtOAc (3×). The organic phases were washed with aqueous saturated NaHCO3 and aqueous 10% NaCl, dried (Na2SO4) and evaporated to give 0.332 g (quant.) of the titled compound as white foam. MS: 510.1 (MH+, 2Cl).

Workup

  1. waitOver night
  2. extractionextracted with EtOAc (3×)
  3. washThe organic phases were washed with aqueous saturated NaHCO3 and aqueous 10% NaCl
  4. dry with materialdried (Na2SO4)
  5. customevaporated

Sources & evidence

ORD record
ord-f95da79bac6f406792bec94a224d73a8
Source dataset
uspto-grants-2013_05
Patent number
US08445674B2

Reaction notes

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