1-Hydroxybenzotriazole → 3-benzoylamino-N-[2-chloro-4-[[[(3-hydroxyphenyl) methyl]amino]carbonyl]benzoyl]-L-alanine, methyl ester

HRID 393062Notes

Reaction equation

HRID 393062 reaction equation
C(N(C(C)C)CC)(C)C.[Cl:10][C:11]1[CH:19]=[C:18]([C:20]([NH:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([OH:30])[CH:25]=2)=[O:21])[CH:17]=[CH:16][C:12]=1[C:13]([OH:15])=O.Cl.[CH3:32][O:33][C:34](=[O:47])[C@H:35]([CH2:37][NH:38][C:39](=[O:46])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)[NH2:36].C1C=CC2N(O)N=NC=2C=1>CN(C)C=O>[C:39]([NH:38][CH2:37][C@@H:35]([C:34]([O:33][CH3:32])=[O:47])[NH:36][C:13](=[O:15])[C:12]1[CH:16]=[CH:17][C:18]([C:20]([NH:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([OH:30])[CH:25]=2)=[O:21])=[CH:19][C:11]=1[Cl:10])(=[O:46])[C:40]1[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 226613972-Chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoic acidHCID 45926097(S)-Methyl 2-amino-3-benzamidopropanoate hydrochloride

Product 1

HCID 1317230313-benzoylamino-N-[2-chloro-4-[[[(3-hydroxyphenyl) methyl]amino]carbonyl]benzoyl]-L-alanine, methyl esterYield 71.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Diisopropylethylamine (27 mL, 147.2 mmol) was added dropwise to a cooled (˜0° C.) solution of 2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoic acid (Example 26; 9.00 g, 29.4 mmol), 3-benzoylamino-L-alanine methyl ester hydrochloride (Example 300; 11.4 g, 44.2 mmol), HTBU (13.4 g, 35.3 mmol) and HOBT (4.8 g, 35.3 mmol) in N,N-dimethylformamide (125 mL). The reaction was allowed to warm to room temperature and to stir for 18 h. The solvent was concentrated under vacuum to remove most of the N,N-dimethylformamide. Ethyl acetate was added and the solution was washed with water (2×150 mL). 1 M HCl (3×100 mL) and brine. The solution was dried (MgSO4), filtered, evaporated, and chromatographed (0-50% acetone/dichloromethane) to give 3-benzoylamino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine, methyl ester (10.7 g, 71%).

Workup

  1. concentrationThe solvent was concentrated under vacuum
  2. customto remove most of the N,N-dimethylformamide
  3. additionEthyl acetate was added
  4. washthe solution was washed with water (2×150 mL)
  5. dry with materialThe solution was dried (MgSO4)
  6. filtrationfiltered
  7. customevaporated
  8. customchromatographed (0-50% acetone/dichloromethane)

Sources & evidence

ORD record
ord-b6d1a42bc10142779fc9e6d0107dbde3
Source dataset
uspto-grants-2004_10
Patent number
US06803384B2

Reaction notes

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