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

HRID 1976952Notes

Reaction equation

HRID 1976952 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([C:11]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([OH:20])[CH:15]=2)=[O:12])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.[CH3:21][O:22][C:23](=[O:44])[C@H:24]([CH2:26][C:27]1[CH:32]=[CH:31][C:30]([NH:33][C:34](=[O:43])[C:35]2[C:40]([Cl:41])=[CH:39][CH:38]=[CH:37][C:36]=2[Cl:42])=[CH:29][CH:28]=1)[NH2:25].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>[CH3:21][O:22][C:23](=[O:44])[C@H:24]([CH2:26][C:27]1[CH:28]=[CH:29][C:30]([NH:33][C:34]([C:35]2[C:40]([Cl:41])=[CH:39][CH:38]=[CH:37][C:36]=2[Cl:42])=[O:43])=[CH:31][CH:32]=1)[NH:25][C:4]([C:3]1[CH:7]=[CH:8][C:9]([C:11]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([OH:20])[CH:15]=2)=[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 219993342-Chloro-4-[[(3-hydroxyphenyl)amino]carbonyl]benzoic acidHCID 233839334-(2,6-Dichlorobenzoylamino)-L-phenylalanine methyl ester

Product 1

HCID 54181036N-[[2-chloro-4-[[(3-hydroxyphenyl)amino]carbonyl]phenyl]carbonyl]-4-[[(2,6-dichlorophenyl)carbonyl]amino]-L-phenylalanine methyl esterYield 40.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In an argon atmosphere, to a stirred solution of 2-chloro-4-[[(3-hydroxyphenyl)amino]carbonyl]benzoic acid (45 mg; 0.1472 mmol), 4-(2,6-dichlorobenzoylamino)-L-phenylalanine methyl ester (60 mg; 0.1488 mmol) and HBTU (59 mg; 0.16 mmol) in dimethylformamide (3 mL) was added DIPEA (0.102 mL; 0.585 mmol). The reaction mixture was stirred for 17 hr at room temperature, then was concentrated to dryness in vacuo and the residue was partitioned between dichloromethane (25 mL) and 0.5 N HCl (10 mL). The organic layer was washed with water and the aqueous layers were backwashed in turn with dichloromethane. The combined dichloromethane extracts were dried (Na2SO4) and evaporated to give 80 mg of crude material that was crystallized from methanol-ethyl acetate to provide 38 mg of N-[[2-chloro-4-[[(3-hydroxyphenyl)amino]carbonyl]phenyl]carbonyl]-4-[[(2,6-dichlorophenyl)carbonyl]amino]-L-phenylalanine methyl ester. mp 230-232° C. FAB HRMS: (C32H26Cl3N3O6) Obs. Mass 654.0952 Calcd. Mass 654.0965 (M+H).

Workup

  1. concentrationwas concentrated to dryness in vacuo
  2. customthe residue was partitioned between dichloromethane (25 mL) and 0.5 N HCl (10 mL)
  3. washThe organic layer was washed with water
  4. dry with materialThe combined dichloromethane extracts were dried (Na2SO4)
  5. customevaporated
  6. customto give 80 mg of crude material that
  7. customwas crystallized from methanol-ethyl acetate

Sources & evidence

ORD record
ord-6b21f31fd9304edbbd8a827f5220dd7f
Source dataset
uspto-grants-2001_05
Patent number
US06229011B1

Reaction notes

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