1-Hydroxybenzotriazole → HCID 59146105, compound

HRID 1512851Notes

Reaction equation

HRID 1512851 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.C1C=CC2N(O)N=NC=2C=1.[F:25][C:26]1[CH:27]=[C:28]2[C:32](=[CH:33][C:34]=1/[C:35](/[NH:38]O)=[N:36]/[H])[NH:31][CH:30]=[C:29]2[CH2:40][CH2:41][C:42]([O:44][CH2:45][CH3:46])=[O:43].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>O1CCCC1.C(OCC)(=O)C.C(Cl)CCl>[Cl:1][C:2]1[CH:3]=[C:4]([C:5]2[O:7][N:36]=[C:35]([C:34]3[CH:33]=[C:32]4[C:28]([C:29]([CH2:40][CH2:41][C:42]([O:44][CH2:45][CH3:46])=[O:43])=[CH:30][NH:31]4)=[CH:27][C:26]=3[F:25])[N:38]=2)[CH:8]=[CH:9][C:10]=1[O:11][CH:12]([CH3:14])[CH3:13]

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 2724141Tetrabutylammonium FluorideHCID 225977283-Chloro-4-(propan-2-yloxy)benzoic acidHCID 178506486HCID 178506486, compound

Product 1

HCID 59146105HCID 59146105, compoundYield 69.1%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-chloro-4-[(1-methylethyl)oxy]benzoic acid (132 mg) in tetrahydrofuran (THF) (12 mL) was added EDC (235 mg) and HOBt (188 mg) and the mixture was stirred at RT for half an hour. Ethyl 3-{5-fluoro-6-[(Z)-(hydroxyamino)(imino)methyl]-1H-indol-3-yl}propanoate (D155) (180 mg) was then added and the resulting mixture was stirred for another 1 hour. Finally, TBAF (642 mg) was added to the solution and the reaction vessel was sealed and heated in Biotage Initiator using initial high at 120° C. for 2 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 eluting with EA and PA to give the designed product ethyl 3-[6-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-5-fluoro-1H-indol-3-yl]propanoate (D156) (200 mg). MS (ES): C24H23ClFN3O4 requires 471.1. found 472.2 (M+H+).

Workup

  1. stirringthe resulting mixture was stirred for another 1 hour
  2. customthe reaction vessel was sealed
  3. temperatureheated in Biotage Initiator
  4. customhigh at 120° C.
  5. customfor 2 hours
  6. temperatureAfter cooling
  7. customthe reaction
  8. washwashed with water (2×60 mL)
  9. concentrationThe organic layer was then concentrated under vacuo
  10. customthe residue was chromatographed on silica gel eluting with EA and PA

Sources & evidence

ORD record
ord-832e60b966ef4a4eac0bd3fc4fec674c
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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