Diisopropylethylamine → 4-[[(2,6-dichlorophenyl)carbonyl]amino]-N-[[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]sulfonyl]phenyl]carbonyl]-L-phenylalanine methyl ester

HRID 1976959Notes

Reaction equation

HRID 1976959 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([S:11]([NH:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([OH:22])[CH:17]=2)(=[O:13])=[O:12])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.[CH3:23][O:24][C:25](=[O:46])[C@H:26]([CH2:28][C:29]1[CH:34]=[CH:33][C:32]([NH:35][C:36]([C:38]2[C:43]([Cl:44])=[CH:42][CH:41]=[CH:40][C:39]=2[Cl:45])=[O:37])=[CH:31][CH:30]=1)[NH2:27].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C)C=O>[CH3:23][O:24][C:25](=[O:46])[C@H:26]([CH2:28][C:29]1[CH:30]=[CH:31][C:32]([NH:35][C:36]([C:38]2[C:43]([Cl:44])=[CH:42][CH:41]=[CH:40][C:39]=2[Cl:45])=[O:37])=[CH:33][CH:34]=1)[NH:27][C:4]([C:3]1[CH:7]=[CH:8][C:9]([S:11]([NH:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([OH:22])[CH:17]=2)(=[O:13])=[O:12])=[CH:10][C:2]=1[Cl:1])=[O:6]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 219993292-Chloro-4-[(3-hydroxybenzylamino)sulfonyl]benzoic acidHCID 233839334-(2,6-Dichlorobenzoylamino)-L-phenylalanine methyl ester

Product 1

HCID 541912724-[[(2,6-dichlorophenyl)carbonyl]amino]-N-[[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]sulfonyl]phenyl]carbonyl]-L-phenylalanine methyl esterYield 54.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 2-chloro-4-[(3-hydroxybenzylamino)sulfonyl]benzoic acid (50 mg; 0.146 mmol), 4-[[(2,6-dichlorophenyl)carbonyl]amino]-L-phenylalanine methyl ester (60 mg; 0.1486 mmol), HBTU (5 mg; 0.15 mmol) and DIPEA (0.102 mL; 0.585 mmol) in dimethylformamide (3 mL) was stirred for 17 hr under argon at room temperature, then was concentrated to dryness under reduced pressure. The residue was partitioned between dichloromethane (25 mL) and 0.5 N HCl (25 mL). The separated aqueous phase was re-extracted with dichloromethane (10 mL), then the organic extacts were washed in turn with water (2×25 mL). The combined dichloromethane layers were dried (Na2SO4) and evaporated to give 90 mg of the crude product as a dark oil. Chromatography of the oil over silica gel (9 g; 4:1 ethyl acetate-hexane) yielded 55 mg of 4-[[(2,6-dichlorophenyl)carbonyl]amino]-N-[[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]sulfonyl]phenyl]carbonyl]-L-phenylalanine methyl ester, as a colorless solid. FAB HRMS: (C31H26Cl3N3O7S) Obs. Mass 690.0639 Calcd. Mass 690.0635 (M+H).

Workup

  1. concentrationwas concentrated to dryness under reduced pressure
  2. customThe residue was partitioned between dichloromethane (25 mL) and 0.5 N HCl (25 mL)
  3. extractionThe separated aqueous phase was re-extracted with dichloromethane (10 mL)
  4. washthe organic extacts were washed in turn with water (2×25 mL)
  5. dry with materialThe combined dichloromethane layers were dried (Na2SO4)
  6. customevaporated
  7. customto give 90 mg of the crude product as a dark oil

Sources & evidence

ORD record
ord-a517b86567e34ff79cf42e4628d53603
Source dataset
uspto-grants-2001_05
Patent number
US06229011B1

Reaction notes

Loading…