4-Methylmorpholine → N-(2-dimethylaminoethyl)-2-oxo-3-(2-oxo-2,3-dihydro-1H-benzimidazol-5-ylmethyl)-2,3-dihydrobenzoxazole-5-carboxamide

HRID 1970867Notes

Reaction equation

HRID 1970867 reaction equation
[O:1]=[C:2]1[N:6]([CH2:7][C:8]2[CH:17]=[CH:16][C:11]3[NH:12][C:13](=[O:15])[NH:14][C:10]=3[CH:9]=2)[C:5]2[CH:18]=[C:19]([C:22]([OH:24])=O)[CH:20]=[CH:21][C:4]=2[O:3]1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.[CH3:53][N:54]([CH3:58])[CH2:55][CH2:56][NH2:57]>CN(C=O)C.O>[CH3:53][N:54]([CH3:58])[CH2:55][CH2:56][NH:57][C:22]([C:19]1[CH:20]=[CH:21][C:4]2[O:3][C:2](=[O:1])[N:6]([CH2:7][C:8]3[CH:17]=[CH:16][C:11]4[NH:12][C:13](=[O:15])[NH:14][C:10]=4[CH:9]=3)[C:5]=2[CH:18]=1)=[O:24]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 66053N,N-DimethylethylenediamineHCID 757711-HydroxybenzotriazoleHCID 595647202-oxo-3-(2-oxo-2,3-dihydro-1H-benzimidazol-5-ylmethyl)-2,3-dihydrobenzoxazole-5-carboxylic acid

Product 1

HCID 59564717N-(2-dimethylaminoethyl)-2-oxo-3-(2-oxo-2,3-dihydro-1H-benzimidazol-5-ylmethyl)-2,3-dihydrobenzoxazole-5-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

330 mg (0.76 mmol) of 2-oxo-3-(2-oxo-2,3-dihydro-1H-benzimidazol-5-yl-methyl)-2,3-dihydrobenzoxazole-5-carboxylic acid are dissolved in 3 ml of DMF, and 294 mg (1.52 mmol) of EDCI, 106 mg (0.76 mmol) of HOBt and 157 μl (1.52 mmol) of N-methylmorpholine are added. 81 mg (0.91 mmol) of 2-dimethylaminoethylamine are subsequently added, and the reaction solution is stirred at room temperature for 3 days. The reaction mixture is subsequently added to water and extracted with dichloromethane. The organic phase is dried over sodium sulfate, evaporated to dryness and purified by column chromatography on silica gel. The product is purified again by preparative HPLC; 100 mg of “A35” trifluoromethylacetate; ESI 397 (M+H), HPLC: Rt=3.89 min (method A).

Workup

  1. extractionextracted with dichloromethane
  2. dry with materialThe organic phase is dried over sodium sulfate
  3. customevaporated to dryness
  4. custompurified by column chromatography on silica gel
  5. customThe product is purified again by preparative HPLC

Sources & evidence

ORD record
ord-efb10128de8141e9a96c7fcc2846bc5b
Source dataset
uspto-grants-2013_04
Patent number
US08431572B2

Reaction notes

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