Dichloromethane → N-(2-diethylamino-ethyl)-4-(2-benzyloxy-acetylamino)-2-methoxy-benzamide

HRID 32288

Reaction equation

HRID 32288 reaction equation
[CH2:1]([O:8][CH2:9][C:10]([OH:12])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)Cl.CN(C)CCCN=C=NCC.[NH2:27][C:28]1[CH:43]=[CH:42][C:31]([C:32]([NH:34][CH2:35][CH2:36][N:37]([CH2:40][CH3:41])[CH2:38][CH3:39])=[O:33])=[C:30]([O:44][CH3:45])[CH:29]=1>O>[CH2:40]([N:37]([CH2:38][CH3:39])[CH2:36][CH2:35][NH:34][C:32](=[O:33])[C:31]1[CH:42]=[CH:43][C:28]([NH:27][C:10](=[O:12])[CH2:9][O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[CH:29][C:30]=1[O:44][CH3:45])[CH3:41]

Participants

6

Reactant 4

HCID 6344Dichloromethane2×HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 773744-Amino-N-[2-(diethylamino)ethyl]-2-methoxybenzamideHCID 290301(Benzyloxy)acetic acid

Product 1

HCID 59793337N-(2-diethylamino-ethyl)-4-(2-benzyloxy-acetylamino)-2-methoxy-benzamideYield 27%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
4 °C

Procedure

664 mg (4 mmol) of benzyloxyacetic acid is introduced into 20 ml of methylene chloride, mixed with 768 mg (4 mmol) of N′-(3-dimethylaminopropyl)-N-ethylcarbodiimide (EDG), and stirred for 0.5 hour at 4° C. Then, 1.06 g (4 mmol) of 4-amino-N-(2-diethylamino-ethyl)-2-methoxy-benzamide in a total of 12 ml of methylene chloride is added to the batch and stirred for 48 hours at room temperature. After 30 ml of water is added, it is extracted twice with 30 ml each of methylene chloride. The organic phase is dried, filtered and concentrated by evaporation. The residue is chromatographed on 20 g of Isolute NH2 (50 μm) with methylene chloride. The correspondingly combined fractions are concentrated by evaporation and chromatographed again on 20 g of Isolute NH2 (50 μm) with a gradient from cyclohexane to cyclohexane:methylene chloride=50:50 as an eluant, and 348 mg (27% of theory) of N-(2-diethylamino-ethyl)-4-(2-benzyloxy-acetylamino)-2-methoxy-benzamide is obtained as an oil.

Workup

  1. stirringstirred for 48 hours at room temperature
  2. extractionit is extracted twice with 30 ml each of methylene chloride
  3. customThe organic phase is dried
  4. filtrationfiltered
  5. concentrationconcentrated by evaporation
  6. customThe residue is chromatographed on 20 g of Isolute NH2 (50 μm) with methylene chloride
  7. concentrationThe correspondingly combined fractions are concentrated by evaporation
  8. customchromatographed again on 20 g of Isolute NH2 (50 μm) with a gradient from cyclohexane to cyclohexane

Sources & evidence

ORD record
ord-82caffa4065a4ce5a8a0b285a7b56e7f
Source dataset
uspto-grants-2008_09
Patent number
US07427390B2

Linked notes

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