1-Hydroxybenzotriazole → HCID 59146137, compound

HRID 1512853Notes

Reaction equation

HRID 1512853 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]([OH:14])=O)[CH:5]=[N:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].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:12]2[O:14][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:5]=[N:6][C:7]=1[O:8][CH:9]([CH3:10])[CH3:11]

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 2724141Tetrabutylammonium FluorideHCID 180705825-Chloro-6-isopropoxynicotinic acidHCID 178506486HCID 178506486, compound

Product 1

HCID 59146137HCID 59146137, compoundYield 60.8%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 5-chloro-6-[(1-methylethyl)oxy]-3-pyridinecarboxylic acid (210 mg) in tetrahydrofuran (THF) (10 mL) was added EDC (373 mg) and HOBt (298 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 microwave 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-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-5-fluoro-1H-indol-3-yl]propanoate (D158) (280 mg). MS (ES): C23H22ClFN4O4 requires 472.1; found 473.2 (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-ba133a4920cc4177b468a0cb464c697a
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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