Tert-butoxycarbonylalanine → {1-[6-Fluoro-1-(3-fluoropyridin-2-yl)-1H-benzoimidazol-2-yl]ethyl}carbamic acid tert-butyl ester

HRID 243115Notes

Reaction equation

HRID 243115 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:15]([F:16])=[CH:14][CH:13]=[CH:12][N:11]=2)[C:5]([NH2:8])=[CH:6][CH:7]=1.[C:17]([O:21][C:22]([NH:24][C@@H:25]([CH3:29])[C:26](O)=O)=[O:23])([CH3:20])([CH3:19])[CH3:18].C1C=NC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>C(Cl)Cl>[C:17]([O:21][C:22](=[O:23])[NH:24][CH:25]([C:26]1[N:9]([C:10]2[C:15]([F:16])=[CH:14][CH:13]=[CH:12][N:11]=2)[C:4]2[CH:3]=[C:2]([F:1])[CH:7]=[CH:6][C:5]=2[N:8]=1)[CH3:29])([CH3:20])([CH3:19])[CH3:18]

Participants

6

Reactant 4

HCID 85082Tert-butoxycarbonylalanineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 681569974-Fluoro-N2-(3-fluoropyridin-2-yl)benzene-1,2-diamine

Product 1

HCID 68156913{1-[6-Fluoro-1-(3-fluoropyridin-2-yl)-1H-benzoimidazol-2-yl]ethyl}carbamic acid tert-butyl esterYield 61%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 4-fluoro-N2-(3-fluoropyridin-2-yl)benzene-1,2-diamine (81 mg, 0.37 mmol), (S)-2-tertbutoxycarbonylaminopropionic acid (76 mg, 0.40 mmol), HOAt (55 mg, 0.40 mmol) and N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (77 mg, 0.40 mmol) in DCM (5 mL) was stirred at 0° C. for 2 h. The reaction mixture was partitioned between DCM and a saturated aqueous solution of NaHCO3. The organic layer was dried and concentrated in vacuo. The resulting residue was taken up in AcOH (5 mL) and heated at 70° C. for 24 h. After cooling to RT, the volatiles were removed in vacuo and the resulting residue partitioned between EtOAc and a saturated aqueous solution of NaHCO3. The organic fraction was washed with water, followed by brine, then dried (Na2SO4) and concentrated in vacuo. The resulting oil was purified by column chromatography (Si—PCC, gradient 0-10% MeOH in EtOAc) to afford the title compound as an orange oil (84 mg, 61%). LCMS (Method C): RT 3.28 min [M+H]+ 375.22

Workup

  1. customThe reaction mixture was partitioned between DCM
  2. customThe organic layer was dried
  3. concentrationconcentrated in vacuo
  4. temperatureheated at 70° C. for 24 h
  5. temperatureAfter cooling to RT
  6. customthe volatiles were removed in vacuo
  7. customthe resulting residue partitioned between EtOAc
  8. washThe organic fraction was washed with water
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated in vacuo
  11. customThe resulting oil was purified by column chromatography (Si—PCC, gradient 0-10% MeOH in EtOAc)

Sources & evidence

ORD record
ord-0418fb699b78497b9d66ab9b86ee6601
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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