1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 68158058, compound

HRID 243134Notes

Reaction equation

HRID 243134 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH3:17])[CH:11]=2)[C:5]([NH2:8])=[CH:6][CH:7]=1.C(OC([NH:25][C@@H:26]([CH3:30])[C:27](O)=O)=O)(C)(C)C.C1C=NC2N(O)N=NC=2C=1.CN(C)CCCN=C=NCC>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]2[N:8]=[C:27]([C@@H:26]([NH2:25])[CH3:30])[N:9]([C:10]3[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH3:17])[CH:11]=3)[C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 85082Tert-butoxycarbonylalanineHCID 181649HOAtHCID 62377108HCID 62377108, compound

Product 1

HCID 68158058HCID 68158058, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

4-Fluoro-N2-(3-methoxyphenyl)benzene-1,2-diamine (0.7 g, 2.99 mmol) was dissolved in DCM (10 mL), under an atmosphere of nitrogen and (S)-2-tert-butoxycarbonylaminopropionic acid (0.63 g, 3.29 mmol) and HOAt (0.45 g, 3.29 mmol) added. The mixture was cooled to 0° C. before N-(3-dimethylaminopropyl)-N′ ethylcarbodiimide (0.63 g, 3.29 mmol) was added portion wise. The reaction mixture was stirred at 0° C. for 1 h, before being allowed to reach RT. It was then diluted with DCM (40 mL) and washed with 10% citric acid and brine (20 mL). The organic fraction was dried (MgSO4), filtered and concentrated in vacuo. The residue was dissolved in acetic acid (10 mL) and heated at 70° C. overnight. The resultant mixture was allowed to cool to RT and concentrated in vacuo to afford a dark brown gum. This was purified by column chromatography (SiO2, gradient 0-5% MeOH in DCM) to afford boc protected title compound as a red gum, which solidified on standing (0.78 g, 68%). This was dissolved in DCM (10 mL) and TFA (3 mL) added. The reaction mixture was stirred at RT for 1 h. The resultant mixture was concentrated in vacuo and the residue dissolved in DCM (40 mL) and stirred vigorously with saturated aqueous NaHCO3 for 10 minutes. The layers were separated and the organic fraction washed with brine (20 mL), dried (MgSO4), filtered and concentrated in vacuo to afford the title compound as a red gum (0.4 g, 70%). LCMS (Method B): RT 1.90 min [M+H]+ 286.0

Workup

  1. additionwas added portion wise
  2. customto reach RT
  3. washwashed with 10% citric acid and brine (20 mL)
  4. dry with materialThe organic fraction was dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residue was dissolved in acetic acid (10 mL)
  8. temperatureheated at 70° C. overnight
  9. temperatureto cool to RT
  10. concentrationconcentrated in vacuo
  11. customto afford a dark brown gum
  12. customThis was purified by column chromatography (SiO2, gradient 0-5% MeOH in DCM)

Sources & evidence

ORD record
ord-a431c349e0be4594b1c88df345ba9650
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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