1-Hydroxybenzotriazole → HCID 67025263, compound

HRID 1512852Notes

Reaction equation

HRID 1512852 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]2[C:33](=[CH:34][C:35]=1/[C:36](/[NH:39]O)=[N:37]/[H])[NH:32][CH:31]=[C:30]2[CH2:41][CH2:42][C:43]([O:45][CH2:46][CH3:47])=[O:44].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>O1CCCC1.C(OCC)(=O)C.C(Cl)CCl>[C:1]([C:3]1[CH:4]=[C:5]([C:6]2[O:8][N:37]=[C:36]([C:35]3[CH:34]=[C:33]4[C:29]([C:30]([CH2:41][CH2:42][C:43]([O:45][CH2:46][CH3:47])=[O:44])=[CH:31][NH:32]4)=[CH:28][C:27]=3[F:26])[N:39]=2)[CH:9]=[CH:10][C:11]=1[O:12][CH:13]([CH3:15])[CH3:14])#[N:2]

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 2724141Tetrabutylammonium FluorideHCID 21956832RP-101124HCID 178506486HCID 178506486, compound

Product 1

HCID 67025263HCID 67025263, compoundYield 55.5%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 3-cyano-4-[(1-methylethyl)oxy]benzoic acid (200 mg) in tetrahydrofuran (THF) (10 mL) was added EDC (374 mg) and HOBt (299 mg). The mixture was stirred for half an hour. Ethyl 3-{5-fluoro-6-[(Z)-(hydroxyamino)(imino)methyl]-1H-indol-3-yl}propanoate (D155) (286 mg) was then added and the resulting mixture was stirred further for 1 hour. Finally, TBAF (1019 mg) was added to the solution and the reaction vessel was sealed and heated in macrowave at 120° C. for two hours. After cooling the reaction, the solution was diluted with ethyl acetate (80 mL) and washed with water (2×60 mL). The organic layer was then concentrated under vacuo and the residue was chromatographed on silica gel to give the designed product ethyl 3-[6-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-5-fluoro-1H-indol-3-yl]propanoate (D157) (250 mg). MS (ES): C25H23FN4O4 requires 462.2; found 463.2 (M+H+).

Workup

  1. stirringthe resulting mixture was stirred further for 1 hour
  2. customthe reaction vessel was sealed
  3. temperatureAfter cooling
  4. customthe reaction
  5. washwashed with water (2×60 mL)
  6. concentrationThe organic layer was then concentrated under vacuo
  7. customthe residue was chromatographed on silica gel

Sources & evidence

ORD record
ord-1974219af25448459dad89bb7073df0b
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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