1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 59146050, compound

HRID 1512836Notes

Reaction equation

HRID 1512836 reaction equation
C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[Cl:22][C:23]1[CH:24]=[C:25]([C:33]([OH:35])=O)[CH:26]=[N:27][C:28]=1[O:29][CH:30]([CH3:32])[CH3:31].[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:33]2[O:35][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:26]=[N:27][C:28]=1[O:29][CH:30]([CH3:31])[CH3:32]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 2724141Tetrabutylammonium FluorideHCID 180705825-Chloro-6-isopropoxynicotinic acidHCID 178506513HCID 178506513, compound

Product 1

HCID 59146050HCID 59146050, compoundYield 105.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

HOBT (211 mg) and EDCI (260 mg) were added to a solution of 5-chloro-6-[(1-methylethyl)oxy]-3-pyridinecarboxylic acid (148 mg) in THF (4 mL). The resulting solution was stirred for 1 hour. Ethyl 3-{5-fluoro-7-[(Z)-(hydroxyamino)(imino)methyl]-1H-indol-3-yl}propanoate (D136) (302 mg) in THF (4 mL) was added, and the reaction mixture was stirred at RT for 1.5 hours. TBAF (780 mg) 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 EA 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-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-5-fluoro-1H-indol-3-yl]propanoate (D139) (341 mg) as a pale yellow solid. δH (CDCl3, 400 MHz): 1.26 (3H, t), 1.47 (6H, d), 2.73 (2H, t), 3.12 (2H, t), 4.15 (2H, q), 5.52 (1H, m), 7.24 (1H, d), 7.47 (1H, dd), 7.86 (1H, dd), 8.43 (1H, d), 8.93 (1H, d), 9.54 (1H, br s). MS (ES): C23H22ClFN4O4 requires 472; found 473.2 (M+H+).

Workup

  1. stirringthe reaction mixture was stirred at RT for 1.5 hours
  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 EA 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-d833c4ec54d742249cde2dd191b77cac
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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