1-Hydroxybenzotriazole → HCID 66961741, compound

HRID 1362677Notes

Reaction equation

HRID 1362677 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.[N:31]1([C:37]2[N:42]=[CH:41][C:40]([CH2:43][NH2:44])=[CH:39][CH:38]=2)[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C>O.C(Cl)CCl.CN(C=O)C>[N:31]1([C:37]2[N:42]=[CH:41][C:40]([CH2:43][NH:44][C:13](=[O:15])/[C:12](=[CH:16]/[C:17]3[CH:22]=[CH:21][C:20]([N:23]4[CH:27]=[C:26]([CH3:28])[N:25]=[CH:24]4)=[C:19]([O:29][CH3:30])[CH:18]=3)/[CH2:11][CH2:10][CH2:9][Cl:8])=[CH:39][CH:38]=2)[CH2:32][CH2:33][O:34][CH2:35][CH2:36]1

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 162273801-[6-(Morpholin-4-yl)pyridin-3-yl]methanamineHCID 66960186(E)-5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid trifluoroacetate

Product 1

HCID 66961741HCID 66961741, compoundYield 92.4%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To an ethanol (50 mL) solution of 2-[6-(morpholin-4-yl)pyridine-3-yl]methylisoindoindol-1,3-dione (3.8 g) obtained above, hydrazine monohydrate (2.95 mL) was added, and heat-refluxing of the reaction solution was carried out for 2 hours. The reaction solution was allowed to be cooled to room temperature, diethyl ether (100 mL) was added to the reaction solution, and the reaction solution was agitated for 30 minutes at room temperature. C-[6-(morpholin-4-yl)pyridine-3-yl]methylamine (3.0 g) was obtained by filtering off insoluble solids in the reaction solution and condensing the obtained filtrate under reduced pressure. To a DMF (30 mL) solution of (E)-5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid trifluoroacetic acid salt (0.20 g) obtained in Example 418 and C-[6-(morpholin-4-yl)pyridine-3-yl]methylamine (0.30 g), HOBT (0.181 g), IPEA (0.388 mL) and EDC (0.257 g) were added at room temperature, and the reaction solution was agitated at room temperature for 12 hours. The reaction solution was added to water and the reaction solution was extracted with ethyl acetate. The obtained organic layer was washed with a saturated salt solution, and concentrated under reduced pressure after dried over anhydrous magnesium sulfate. The residue was purified by silica gel column chromatography (elution solvent: from heptane-ethyl acetate system to methanol-ethyl acetate system) and 0.21 g of (E)-5-chloro-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene]valeric acid [6-(morpholin-4-yl)pyridine-3-yl]methyl amide was obtained.

Workup

  1. filtrationby filtering off insoluble solids
  2. customin the reaction solution and condensing the obtained filtrate under reduced pressure
  3. extractionthe reaction solution was extracted with ethyl acetate
  4. washThe obtained organic layer was washed with a saturated salt solution
  5. concentrationconcentrated under reduced pressure
  6. dry with materialafter dried over anhydrous magnesium sulfate
  7. customThe residue was purified by silica gel column chromatography (elution solvent: from heptane-ethyl acetate system to methanol-ethyl acetate system)

Sources & evidence

ORD record
ord-271467abb23b4dd3b2ca24b675505c20
Source dataset
uspto-grants-2011_02
Patent number
US07880009B2

Reaction notes

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