Hydrochloric Acid → N-[2-chloro-4-[[(3-hydroxyphenyl) carbonyl]aminomethyl]benzoyl]-3-benzoylamino-L-alanine

HRID 393104Notes

Reaction equation

HRID 393104 reaction equation
[NH2:1][CH2:2][C:3]1[CH:25]=[CH:24][C:6]([C:7]([NH:9][C@H:10]([C:21]([OH:23])=[O:22])[CH2:11][NH:12][C:13](=[O:20])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:8])=[C:5]([Cl:26])[CH:4]=1.[OH:27][C:28]1[CH:29]=[C:30]([CH:34]=[CH:35][CH:36]=1)[C:31](O)=[O:32].C1(N=C=NC2CCCCC2)CCCCC1.O.[OH-].[Li+].Cl>O1CCCC1.CN(C=O)C.O.CO>[Cl:26][C:5]1[CH:4]=[C:3]([CH2:2][NH:1][C:31]([C:30]2[CH:34]=[CH:35][CH:36]=[C:28]([OH:27])[CH:29]=2)=[O:32])[CH:25]=[CH:24][C:6]=1[C:7]([NH:9][C@H:10]([C:21]([OH:23])=[O:22])[CH2:11][NH:12][C:13](=[O:20])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:8]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 74203-Hydroxybenzoic AcidHCID 10868DicyclohexylcarbodiimideHCID 168937Lithium hydroxide, monohydrateHCID 53810550N-[4-(aminomethyl)-2-chlorobenzoyl]-3-benzoylamino-L-alanine

Product 1

HCID 59977275N-[2-chloro-4-[[(3-hydroxyphenyl) carbonyl]aminomethyl]benzoyl]-3-benzoylamino-L-alanineYield 9.5%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Procedure

A mixture of N-[4-(aminomethyl)-2-chlorobenzoyl]-3-benzoylamino-L-alanine (Example 363; 100 mg, 0.26 mmol), 3-hydroxybenzoic acid (40 mg, 0.29 mmol) and dicyclohexylcarbodiimide (60 mg, 0.29 mmol) in tetrahydrofuran/DMF (4:1; 2.5 mL) was stirred at room temperature overnight. Methanol (1 mL) and a solution of lithium hydroxide monohydrate (100 mg, 2.4 mmol) in water (1 mL) were added and the solution was stirred at room temperature overnight. The solution was made acidic with 1 M HCl and extracted with ethyl acetate. The ethyl acetate was evaporated and the residue purified by HPLC to give N-[2-chloro-4-[[(3-hydroxyphenyl)carbonyl]aminomethyl]benzoyl]-3-benzoylamino-L-alanine (12.2 mg, 9%) as a white solid.

Workup

  1. stirringthe solution was stirred at room temperature overnight
  2. extractionextracted with ethyl acetate
  3. customThe ethyl acetate was evaporated
  4. customthe residue purified by HPLC

Sources & evidence

ORD record
ord-1a46c9bd114044939343eab4c34d99e4
Source dataset
uspto-grants-2004_10
Patent number
US06803384B2

Reaction notes

Loading…