Trifluoroacetic acid → (2S)-2-[[1-cyclohexyl-2-(3-furyl)benzimidazole-5-carbonyl]amino]-3-(4-hydroxyphenyl)propanoic acid

HRID 1018243Notes

Reaction equation

HRID 1018243 reaction equation
[CH:1]1([N:7]2[C:11]3[CH:12]=[CH:13][C:14]([C:16](O)=[O:17])=[CH:15][C:10]=3[N:9]=[C:8]2[C:19]2[CH:23]=[CH:22][O:21][CH:20]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C.Cl.C[O:57][C:58](=[O:69])[C@H:59]([CH2:61][C:62]1[CH:67]=[CH:66][C:65]([OH:68])=[CH:64][CH:63]=1)[NH2:60].[OH-].[Na+].C(O)(C(F)(F)F)=O>CN(C=O)C>[CH:1]1([N:7]2[C:11]3[CH:12]=[CH:13][C:14]([C:16]([NH:60][C@@H:59]([CH2:61][C:62]4[CH:67]=[CH:66][C:65]([OH:68])=[CH:64][CH:63]=4)[C:58]([OH:57])=[O:69])=[O:17])=[CH:15][C:10]=3[N:9]=[C:8]2[C:19]2[CH:23]=[CH:22][O:21][CH:20]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

8

Reactant 6

HCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 76956Methyl tyrosinate hydrochlorideHCID 81531DiisopropylethylamineHCID 4911131-Cyclohexyl-2-(furan-3-yl)-1H-benzimidazole-5-carboxylic acidHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate

Product 1

HCID 490759(2S)-2-[[1-cyclohexyl-2-(3-furyl)benzimidazole-5-carbonyl]amino]-3-(4-hydroxyphenyl)propanoic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The carboxylic acid of example 2 (0.075 g, 0.24 mmol) and TBTU (1.2 equiv., 0.29 mmol, 0.093 g) were dissolved in DMF (0.5 mL) and DIEA (5 equiv., 1.2 mmol, 0.21 mL) was added followed by tyrosine methyl ester hydrochloride (1.2 equiv., 0.29 mmol, 0.036 g). The mixture was stirred 30 min at room temperature. The reaction mixture was added drop-wise to 1 N NaOH (10 mL) and the mixture stirred until complete hydrolysis of the methyl ester (as determined by HPLC analysis). The pH of the solution was then adjusted to 5-6 by drop-wise addition of 1 NHCl. The gray precipitate that formed was collected by filtration, washed with water and dried (125 mg). The solid was further purified by reversed-phase HPLC using 0.1% TFA—0.1% TFA in acetonitrile gradients to give after lyophilisation, the TFA salt of the title compound as a white amorphous solid (35 mg).

Workup

  1. additionThe pH of the solution was then adjusted to 5-6 by drop-wise addition of 1 NHCl
  2. customThe gray precipitate that formed
  3. filtrationwas collected by filtration
  4. washwashed with water
  5. customdried (125 mg)
  6. customThe solid was further purified by reversed-phase
  7. customto give after lyophilisation

Sources & evidence

ORD record
ord-f567da91ac36458186f4db077ef5b7e5
Source dataset
uspto-grants-2002_11
Patent number
US06479508B1

Reaction notes

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