1-Hydroxybenzotriazole → HCID 59146030, compound

HRID 1512859Notes

Reaction equation

HRID 1512859 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[O:12][CH:13]([CH3:15])[CH3:14])[C:6]([OH:8])=O)#[N:2].C1C=CC2N(O)N=NC=2C=1.[F:26][C:27]1[CH:28]=[C:29](/[C:43](/[NH:46]O)=[N:44]/[H])[CH:30]=[C:31]2[C:35]=1[NH:34][C:33]([CH2:36][CH2:37][C:38]([O:40][CH2:41][CH3:42])=[O:39])=[CH:32]2.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>O1CCCC1.C(Cl)CCl>[C:1]([C:3]1[CH:4]=[C:5]([C:6]2[O:8][N:44]=[C:43]([C:29]3[CH:30]=[C:31]4[C:35](=[C:27]([F:26])[CH:28]=3)[NH:34][C:33]([CH2:36][CH2:37][C:38]([O:40][CH2:41][CH3:42])=[O:39])=[CH:32]4)[N:46]=2)[CH:9]=[CH:10][C:11]=1[O:12][CH:13]([CH3:15])[CH3:14])#[N:2]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 2724141Tetrabutylammonium FluorideHCID 21956832RP-101124HCID 178506512HCID 178506512, compound

Product 1

HCID 59146030HCID 59146030, compoundYield 53.3%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-cyano-4-[(1-methylethyl)oxy]benzoic acid (150 mg) in tetrahydrofuran (30 mL) stirred at room temperature was added EDC (280 mg) and HOBT (223 mg). The reaction mixture was stirred at room temperature for 0.5 h. Then ethyl 3-{7-fluoro-5-[(Z)-(hydroxyamino)(imino)methyl]-1H-indol-2-yl}propanoate (D163) (214 mg) was added. The reaction mixture was stirred at room temperature for an hour, and then TBAF (763 mg) was added. The reaction mixture was sealed and heated in Biotage Initiator using initial high to 120° C. for 2 hrs. After cooling the reaction, the solvent was removed. The residue was diluted with EtOAc (30 mL). The organic phase was washed with water (25 mL×4) and dried over sodium sulphate and evaporated in vacuo. The crude product was purified by column chromatography to give ethyl 3-[5-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-7-fluoro-1H-indol-2-yl]propanoate (D165) (180 mg) as a white solid. MS (ES): C25H23FN4O4 requires 462; found 463.2 (M+H+).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for an hour
  2. customThe reaction mixture was sealed
  3. temperatureheated in Biotage Initiator
  4. customhigh to 120° C.
  5. customfor 2 hrs
  6. temperatureAfter cooling
  7. customthe reaction
  8. customthe solvent was removed
  9. additionThe residue was diluted with EtOAc (30 mL)
  10. washThe organic phase was washed with water (25 mL×4)
  11. dry with materialdried over sodium sulphate
  12. customevaporated in vacuo
  13. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-bdeb81ab41b44f15b4d5572cac89d1df
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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