Tert-butoxycarbonylalanine → 2-((S)-1-Aminoethyl)-5-fluoro-3-phenyl-3H-benzoimidazole-4-carboxylic acid methyl ester dihydrochloride
Reaction equation
[CH3:1][O:2][C:3](=[O:19])[C:4]1[C:9]([F:10])=[CH:8][CH:7]=[C:6]([NH2:11])[C:5]=1[NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[CH3:20][C@H:21]([NH:25]C(OC(C)(C)C)=O)[C:22](O)=O.C1C=NC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[ClH:54]>C(Cl)Cl.O>[ClH:54].[ClH:54].[CH3:1][O:2][C:3]([C:4]1[C:5]2[N:12]([C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:20]([C@@H:21]([NH2:25])[CH3:22])=[N:11][C:6]=2[CH:7]=[CH:8][C:9]=1[F:10])=[O:19]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 0 °C
Procedure
To a solution of 3-amino-6-fluoro-2-phenylaminobenzoic acid methyl ester (1 g, 3.8 mmol), Boc-ala-OH (727 mg, 3.8 mmol) and HOAT (522 mg, 3.8 mmol) in DCM (20 mL) at 0° C. was added N-(3-dimethylaminopropyl)-n′-ethylcarbodiimide hydrochloride (810 mg, 4.2 mmol) and the reaction mixture stirred at 0° C. for 2 h. The reaction mixture was diluted with water and extracted with DCM (3×10 mL). The combined organic fractions were washed with brine, dried (MgSO4) and concentrated in vacuo. The residue was dissolved in HCl in dioxane (20 mL, 4 M) and the reaction mixture heated at 75° C. for 45 min. The reaction mixture was concentrated in vacuo to give the title product as a dark purple solid (1.48 g, 100%). LCMS (Method C): RT=1.95 min, [M+H]+=314.
Workup
- extractionextracted with DCM (3×10 mL)
- washThe combined organic fractions were washed with brine
- dry with materialdried (MgSO4)
- concentrationconcentrated in vacuo
- dissolutionThe residue was dissolved in HCl in dioxane (20 mL, 4 M)
- temperaturethe reaction mixture heated at 75° C. for 45 min
- concentrationThe reaction mixture was concentrated in vacuo
Sources & evidence
- ORD record
- ord-6aefcb86734848dd84833d03bafce271
- Source dataset
- uspto-grants-2014_02
- Patent number
- US08653089B2
Reaction notes
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