1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 59146118, compound

HRID 1512834Notes

Reaction equation

HRID 1512834 reaction equation
C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[Cl:22][C:23]1[CH:24]=[C:25]([CH:29]=[CH:30][C:31]=1[O:32][CH:33]([CH3:35])[CH3:34])[C:26]([OH:28])=O.[F:36][C:37]1[CH:38]=[C:39]2[C:43](=[C:44](/[C:46](/[NH:49]O)=[N:47]/[H])[CH:45]=1)[NH:42][CH:41]=[C:40]2[CH2:51][CH2:52][C:53]([O:55][CH2:56][CH3:57])=[O:54].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[Cl:22][C:23]1[CH:24]=[C:25]([C:26]2[O:28][N:47]=[C:46]([C:44]3[CH:45]=[C:37]([F:36])[CH:38]=[C:39]4[C:43]=3[NH:42][CH:41]=[C:40]4[CH2:51][CH2:52][C:53]([O:55][CH2:56][CH3:57])=[O:54])[N:49]=2)[CH:29]=[CH:30][C:31]=1[O:32][CH:33]([CH3:35])[CH3:34]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 2724141Tetrabutylammonium FluorideHCID 225977283-Chloro-4-(propan-2-yloxy)benzoic acidHCID 178506513HCID 178506513, compound

Product 1

HCID 59146118HCID 59146118, compoundYield 86.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

HOBT (216 mg) and EDCI (273 mg) were added to a solution of 3-chloro-4-[(1-methylethyl)oxy]benzoic acid (D32) (151 mg) in THF (4 mL). The reaction mixture was stirred at RT for 1 hour. Ethyl 3-{5-fluoro-7-[(Z)-(hydroxyamino)(imino)methyl]-1H-indol-3-yl}propanoate (D136) (268 mg) in THF (4 mL) was added. Then stirring continued overnight. TBAF (1.18 g) was then added. The reaction vessel was sealed and heated in Biotage Initiator using initial normal to 120° C. for 1.5 hours. After cooling, the reaction was quenched with water, and extracted with EtOAc for 3 times. The combined organic solution was washed with brine, and dried over anhydrous sodium sulfate. The dried solution was concentrated. 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)-5-fluoro-1H-indol-3-yl]propanoate (D137) (287 mg) as a pale yellow solid. MS (ES): C24H23ClFN3O4 requires 471; found 472.2 (M+H+).

Workup

  1. stirringThen stirring continued overnight
  2. customThe reaction vessel was sealed
  3. temperatureheated in Biotage Initiator
  4. customnormal to 120° C.
  5. customfor 1.5 hours
  6. temperatureAfter cooling
  7. customthe reaction was quenched with water
  8. extractionextracted with EtOAc for 3 times
  9. washThe combined organic solution was washed with brine
  10. dry with materialdried over anhydrous sodium sulfate
  11. concentrationThe dried solution was concentrated
  12. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-af491b96451d456998ebb782f25efc13
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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