1-Hydroxybenzotriazole → (e)-5-Chloro-2-[3-methoxy-4-(4-methyl-1h-imidazol-1-yl)benzylidene]valeric acid[3-fluoro-4-(morpholin-4-yl)benzyl]amide

HRID 1362673Notes

Reaction equation

HRID 1362673 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:33]=[C:34]([CH:37]=[CH:38][C:39]=1[N:40]1[CH2:45][CH2:44][O:43][CH2:42][CH2:41]1)[CH2:35][NH2:36].C(N(C(C)C)CC)(C)C.C1C=CC2N(O)N=NC=2C=1>C(OCC)(=O)C.O.C(Cl)CCl.CN(C=O)C>[F:31][C:32]1[CH:33]=[C:34]([CH:37]=[CH:38][C:39]=1[N:40]1[CH2:45][CH2:44][O:43][CH2:42][CH2:41]1)[CH2:35][NH:36][C:13](=[O:15])/[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)/[CH2:11][CH2:10][CH2:9][Cl:8]

Participants

9

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 11572017[3-Fluoro-4-(morpholin-4-yl)phenyl]methanamineHCID 669601895-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid trifluoroacetate

Product 1

HCID 66961400(e)-5-Chloro-2-[3-methoxy-4-(4-methyl-1h-imidazol-1-yl)benzylidene]valeric acid[3-fluoro-4-(morpholin-4-yl)benzyl]amideYield 57.5%

Reagents, catalysts & solvents 4

HCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a DMF (4.0 mL) solution of 5-chloro-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene]-valeric acid trifluoroacetic acid salt (200 mg) obtained in Example 418 and 3-fluoro-4-(morpholin-4-yl)benzylamine (112 mg), IPEA (231 mg), EDC (171 mg) and HOBT (120 mg) were added one by one, and the reaction solution was agitated at room temperature overnight. After confirming disappearance of the starting materials, water and ethyl acetate were added to the reaction solution, and the organic layer was partitioned. After the obtained organic layer was washed with a saturated saline solution, it was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. 135 mg of the title compound was obtained by purifying the obtained residue by silica gel chromatography (elution solvent: ethyl acetate->ethyl acetate:methanol=90:10). The physical properties of the compound are as follows.

Workup

  1. additionwere added to the reaction solution
  2. customthe organic layer was partitioned
  3. washAfter the obtained organic layer was washed with a saturated saline solution, it
  4. dry with materialwas dried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-dfb9b4d688fd422f98571c783cd2a55e
Source dataset
uspto-grants-2011_02
Patent number
US07880009B2

Reaction notes

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