1-Hydroxybenzotriazole → 4-benzyloxy-N-{2-[4-(3-methyl-thiophene-2-carbonyl)-piperazin-1-yl]-2-oxo-ethyl}-benzamide

HRID 1177840Notes

Reaction equation

HRID 1177840 reaction equation
[CH3:1][C:2]1[CH:6]=[CH:5][S:4][C:3]=1[C:7]([OH:9])=O.[CH2:10]([O:17][C:18]1[CH:35]=[CH:34][C:21]([C:22]([NH:24][CH2:25][C:26](=[O:33])[N:27]2[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]2)=[O:23])=[CH:20][CH:19]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C.O>[CH2:10]([O:17][C:18]1[CH:35]=[CH:34][C:21]([C:22]([NH:24][CH2:25][C:26]([N:27]2[CH2:32][CH2:31][N:30]([C:7]([C:3]3[S:4][CH:5]=[CH:6][C:2]=3[CH3:1])=[O:9])[CH2:29][CH2:28]2)=[O:33])=[O:23])=[CH:20][CH:19]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 902693-Methyl-2-thenoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 595595894-benzyloxy-N-(2-oxo-2-piperazin-1-yl-ethyl)-benzamide

Product 1

HCID 251659084-benzyloxy-N-{2-[4-(3-methyl-thiophene-2-carbonyl)-piperazin-1-yl]-2-oxo-ethyl}-benzamideYield 46%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

3-Methyl-2-thiophene carboxylic acid (74 mg, 0.53 mmol) was added to 4-benzyloxy-N-(2-oxo-2-piperazin-1-yl-ethyl)-benzamide (155 mg, 0.44 mmol) in DMF (5 mL). EDCI.HCl (126 mg, 0.66 mmol), HOBT (71 mg, 0.53 mmol) and DIPEA (227 μL, 1.32 mmol) were then added and the resulting mixture was allowed to stir at room temperature overnight. Water was then added and the product was extracted with EtOAc and washed with brine. The organic phase was dried over Na2SO4 and concentrated under reduced pressure to afford a crude product. Column chromatography purification (using neutral alumina 90:10 EtOAc:MeOH as the eluent) afforded 4-benzyloxy-N-{2-[4-(3-methyl-thiophene-2-carbonyl)-piperazin-1-yl]-2-oxo-ethyl}-benzamide in 46% yield. LC-MS purity: 87%. 1H NMR (DMSO-D6): δ 8.4 (t, 1H), 7.8 (d, 2H), 7.6 (d, 1H), 7.4 (m, 5H), 7.1 (d, 2H), 6.9 (d, 1H), 5.2 (s, 2H), 4.2 (d, 2H), 3.5 (d, 8H), 2.3 (s, 3H).

Workup

  1. extractionthe product was extracted with EtOAc
  2. washwashed with brine
  3. dry with materialThe organic phase was dried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customto afford a crude product
  6. customColumn chromatography purification (

Sources & evidence

ORD record
ord-d35096eea9a24cf6ab791eb387a96391
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

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