1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Ethyl 3-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-6-fluoro-1H-indol-3-yl]propanoate

HRID 1512842Notes

Reaction equation

HRID 1512842 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[O:11][CH:12]([CH3:14])[CH3:13])[C:5]([OH:7])=O.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[F:36][C:37]1[C:45](/[C:46](/[NH:49]O)=[N:47]/[H])=[C:44]2[C:40]([C:41]([CH2:51][CH2:52][C:53]([O:55][CH2:56][CH3:57])=[O:54])=[CH:42][NH:43]2)=[CH:39][CH:38]=1>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C:5]2[O:7][N:47]=[C:46]([C:45]3[C:37]([F:36])=[CH:38][CH:39]=[C:40]4[C:44]=3[NH:43][CH:42]=[C:41]4[CH2:51][CH2:52][C:53]([O:55][CH2:56][CH3:57])=[O:54])[N:49]=2)[CH:8]=[CH:9][C:10]=1[O:11][CH:12]([CH3:14])[CH3:13]

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 225977283-Chloro-4-(propan-2-yloxy)benzoic acidHCID 178506517HCID 178506517, compound

Product 1

HCID 59146158Ethyl 3-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-6-fluoro-1H-indol-3-yl]propanoateYield 47.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To the solution of 3-chloro-4-[(1-methylethyl)oxy]benzoic acid (D32) (676 mg) in tetrahydrofuran (50 mL) were added EDCI (824 mg) and HOBT (658 mg). The resulting solution was stirred at room temperature for 1 hour. Then ethyl 3-{6-fluoro-7-[(Z)-(hydroxyamino)(imino)methyl]-1H-indol-3-yl}propanoate (D145) (840 mg) was added and the solution was stirred at room temperature for another 2 hours. THF was removed in vacuo and the residue was dissolved in ethyl acetate (50 mL), washed with water (2×10 mL) and dried over sodium sulphate. The organic phase was concentrated. The residue was dissolved in THF (3 mL), TBAF (3 g) was added and the reaction solution was stirred under microwave (120° C., 2.5 hours). The reaction solution was poured into ethyl acetate (100 mL), washed with water (3×20 mL), dried over sodium sulphate. The organic phase was concentrate and the residue was purified by column chromatography to afford ethyl 3-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-6-fluoro-1H-indol-3-yl]propanoate (D146) (640 mg) as an off white solid. MS (ES): C24H23ClFN3O4 requires 471; found 472.2 (M+H+).

Workup

  1. stirringthe solution was stirred at room temperature for another 2 hours
  2. customTHF was removed in vacuo
  3. dissolutionthe residue was dissolved in ethyl acetate (50 mL)
  4. washwashed with water (2×10 mL)
  5. dry with materialdried over sodium sulphate
  6. concentrationThe organic phase was concentrated
  7. dissolutionThe residue was dissolved in THF (3 mL)
  8. additionTBAF (3 g) was added
  9. stirringthe reaction solution was stirred under microwave (120° C., 2.5 hours)
  10. additionThe reaction solution was poured into ethyl acetate (100 mL)
  11. washwashed with water (3×20 mL)
  12. dry with materialdried over sodium sulphate
  13. concentrationThe organic phase was concentrate
  14. customthe residue was purified by column chromatography

Sources & evidence

ORD record
ord-81cee3b06bcf4328890b085a35068772
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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