Triethylamine → methyl N-({3'-fluoro-4'-[(6-fluoro-1,3-benzothiazol-2-yl)amino]biphenyl-4-yl}carbonyl)-L-valinate

HRID 2356817Notes

Reaction equation

HRID 2356817 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:19]2[CH:24]=[CH:23][C:22]([C:25](O)=[O:26])=[CH:21][CH:20]=2)[CH:5]=[CH:6][C:7]=1[NH:8][C:9]1[S:10][C:11]2[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:12]=2[N:13]=1.Cl.[CH3:29][O:30][C:31](=[O:37])[C@H:32]([CH:34]([CH3:36])[CH3:35])[NH2:33].C(N(CC)CC)C.ON1C2C=CC=CC=2N=N1.C(N=C=NC(C)C)(C)C>C(Cl)Cl.CCOC(C)=O.CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([C:19]2[CH:24]=[CH:23][C:22]([C:25]([NH:33][C@H:32]([C:31]([O:30][CH3:29])=[O:37])[CH:34]([CH3:36])[CH3:35])=[O:26])=[CH:21][CH:20]=2)[CH:5]=[CH:6][C:7]=1[NH:8][C:9]1[S:10][C:11]2[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:12]=2[N:13]=1

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 12734DiisopropylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 111190Methyl valinate hydrochlorideHCID 7147096HCID 7147096, compound

Product 1

HCID 59009703methyl N-({3'-fluoro-4'-[(6-fluoro-1,3-benzothiazol-2-yl)amino]biphenyl-4-yl}carbonyl)-L-valinate

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

3′-Fluoro-4′-[(6-fluoro-1,3-benzothiazol-2-yl)amino]biphenyl-4-carboxylic acid (0.084 g, 0.22 mmol) and L-valine methyl ester hydrochloride (0.044 g, 0.26 mmol) were suspended in CH2Cl2 (5 mL), and triethylamine (0.04 mL, 0.26 mmol), 1-hydroxybenzotriazole (0.0296 g, 0.22 mmol), and N,N′-diisopropylcarbodiimide (0.030 mL, 0.22 mmol) were added. DMF (2.0 mL) was added to achieve dissolution, and the reaction mixture was stirred at rt overnight. The reaction mixture was diluted with EtOAc (50 mL) and was washed with water (2×50 mL) and brine (50 mL). The combined organic phases were dried over MgSO4, filtered, and concentrated in vacuo. The crude material was purified by flash column chromatography (Biotage® system; 30-40% EtOAc/Hexanes gradient). This yielded 90.4 mg (83%) of the desired product as a white solid.

Workup

  1. dissolutiondissolution
  2. washwas washed with water (2×50 mL) and brine (50 mL)
  3. dry with materialThe combined organic phases were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by flash column chromatography (Biotage® system; 30-40% EtOAc/Hexanes gradient)

Sources & evidence

ORD record
ord-a719b61d202b46cc9249a4da68c76fea
Source dataset
uspto-grants-2010_07
Patent number
US07759376B2

Reaction notes

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