1-Hydroxybenzotriazole → Pentanamide, 5-chloro-N-[(1S)-1-(4-fluorophenyl)ethyl]-2-[[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]methylene]-, (2E)-

HRID 1362670Notes

Reaction equation

HRID 1362670 reaction equation
FC(F)(F)C(O)=O.[Cl:8][CH2:9][CH2:10][CH2:11][C:12](=[CH:16][C:17]1[CH:22]=[CH:21][C:20]([N:23]2[CH:27]=[C:26]([CH3:28])[N:25]=[CH:24]2)=[C:19]([O:29][CH3:30])[CH:18]=1)[C:13]([OH:15])=O.[F:31][C:32]1[CH:37]=[CH:36][C:35]([C@@H:38]([NH2:40])[CH3:39])=[CH:34][CH:33]=1.C(N(C(C)C)CC)(C)C.C1C=CC2N(O)N=NC=2C=1>C(Cl)CCl.CN(C=O)C>[F:31][C:32]1[CH:37]=[CH:36][C:35]([C@@H:38]([NH:40][C:13](=[O:15])/[C:12](=[CH:16]/[C:17]2[CH:22]=[CH:21][C:20]([N:23]3[CH:27]=[C:26]([CH3:28])[N:25]=[CH:24]3)=[C:19]([O:29][CH3:30])[CH:18]=2)/[CH2:11][CH2:10][CH2:9][Cl:8])[CH3:39])=[CH:34][CH:33]=1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2779063(S)-1-(4-Fluorophenyl)-ethylamineHCID 669601895-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid trifluoroacetate

Product 1

HCID 66961696Pentanamide, 5-chloro-N-[(1S)-1-(4-fluorophenyl)ethyl]-2-[[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]methylene]-, (2E)-Yield 48%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6228DimethylformamideSolvent

Procedure

To a DMF (50 mL) solution of 5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid trifluoroacetic acid salt (8.00 g) and (S)-1-(4-fluorophenyl)ethylamine (2.60 g), IPEA (12.4 mL), EDC (6.82 g) and HOBT (4.81 g) were added one by one, and the reaction solution was agitated at room temperature overnight. After confirming disappearance of the starting materials, the solvent was concentrated under reduced pressure, water and ethyl acetate were added to the residue, and the organic layer was partitioned. After the organic layer was washed with a saturated saline solution, it was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The obtained residue was purified by silica gel chromatography (elution solvent: heptane-ethyl acetate=2:3->1:1->ethyl acetate), and 3.90 g of the title compound was obtained. The physical properties of the compound are as follows.

Workup

  1. concentrationthe solvent was concentrated under reduced pressure, water and ethyl acetate
  2. additionwere added to the residue
  3. customthe organic layer was partitioned
  4. washAfter the organic layer was washed with a saturated saline solution, it
  5. dry with materialwas dried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe obtained residue was purified by silica gel chromatography (elution solvent: heptane-ethyl acetate=2:3->1:1->ethyl acetate)

Sources & evidence

ORD record
ord-975f0203c7b14835b27d08a8d4e12f11
Source dataset
uspto-grants-2011_02
Patent number
US07880009B2

Reaction notes

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