1,2-Dichloroethane → (2r)-3-[(4-{[1h-Benzimidazol-2-yl(4-tert-butylcyclohexyl)amino]methyl}benzoyl)-amino]-2-hydroxypropanoic acid

HRID 229987Notes

Reaction equation

HRID 229987 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[N:10]([CH2:21][C:22]1[CH:30]=[CH:29][C:25]([C:26](O)=[O:27])=[CH:24][CH:23]=1)[CH:11]1[CH2:16][CH2:15][CH:14]([C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:13][CH2:12]1.C[O:32][C:33](=[O:38])[CH:34]([OH:37])[CH2:35][NH2:36].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C.[Li+].[OH-].C(O)(C(F)(F)F)=O>CN(C=O)C.O>[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[N:10]([CH2:21][C:22]1[CH:30]=[CH:29][C:25]([C:26]([NH:36][CH2:35][C@@H:34]([OH:37])[C:33]([OH:32])=[O:38])=[O:27])=[CH:24][CH:23]=1)[CH:11]1[CH2:16][CH2:15][CH:14]([C:17]([CH3:20])([CH3:18])[CH3:19])[CH2:13][CH2:12]1

Participants

10

Reactant 7

HCID 111,2-DichloroethaneHCID 3939Lithium HydroxideHCID 6422Trifluoroacetic acidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 11105589Methyl 3-amino-2-hydroxypropanoateHCID 688356554-{[1h-Benzimidazol-2-yl(4-tert-butylcyclohexyl)amino]methyl}benzoic acid

Product 1

HCID 57758798(2r)-3-[(4-{[1h-Benzimidazol-2-yl(4-tert-butylcyclohexyl)amino]methyl}benzoyl)-amino]-2-hydroxypropanoic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of the title compound of Example 1 Step D (0.04 mmol, 16 mg), the hydrochloride salt of 2-hydroxy β-alanine methyl ester (0.06 mmol, 9 mg), HOBt (0.1 mmol, 15 mg), and EDC (0.12 mmol, 23 mg) in 0.4 mL of DMF was added DIEA (0.2 mmol, 35 μL). After 3 h the reaction was partitioned into EtOAc/brine. The organic phase was dried with MgSO4 and concentrated under reduced pressure. The residue was taken up in 1 mL of dioxane and a solution of LiOH (1 mmol, 24 mg) in 0.5 mL of H2O was added. The reaction was stirred at ambient temperature overnight, acidified with TFA and the product was purified by reverse-phase chromatography (Condition A) and lyophilized, affording the title compound as a white solid. MS (ESI): m/z 493 (M+H). HPLC A: 1.73 min.

Workup

  1. customAfter 3 h the reaction was partitioned into EtOAc/brine
  2. dry with materialThe organic phase was dried with MgSO4
  3. concentrationconcentrated under reduced pressure
  4. customthe product was purified by reverse-phase chromatography (Condition A) and

Sources & evidence

ORD record
ord-d464e379e9b44668aa1fbe1e62a81124
Source dataset
uspto-grants-2009_07
Patent number
US07563815B2

Reaction notes

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