1-Hydroxybenzotriazole → HCID 59146170, compound

HRID 1512860Notes

Reaction equation

HRID 1512860 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](/[C:42](/[NH:45]O)=[N:43]/[H])[CH:29]=[C:30]2[C:34]=1[NH:33][C:32]([CH2:35][CH2:36][C:37]([O:39][CH2:40][CH3:41])=[O:38])=[CH:31]2.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>O1CCCC1.C(Cl)CCl>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:14][N:43]=[C:42]([C:28]3[CH:29]=[C:30]4[C:34](=[C:26]([F:25])[CH:27]=3)[NH:33][C:32]([CH2:35][CH2:36][C:37]([O:39][CH2:40][CH3:41])=[O:38])=[CH:31]4)[N:45]=2)[CH:5]=[N:6][C:7]=1[O:8][CH:9]([CH3:10])[CH3:11]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 2724141Tetrabutylammonium FluorideHCID 180705825-Chloro-6-isopropoxynicotinic acidHCID 178506512HCID 178506512, compound

Product 1

HCID 59146170HCID 59146170, compoundYield 74.4%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-chloro-6-[(1-methylethyl)oxy]-3-pyridinecarboxylic acid (368 mg) in tetrahydrofuran (30 mL) stirred at room temperature was added EDC (654 mg) and HOBT (522 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) (500 mg) was added. The reaction mixture was stirred at room temperature for an hour, and then TBAF (1.78 g) was added. The reaction mixture was sealed and heated in Biotage Initiator using initial high to 120° C. for 0.5 h. After cooling the reaction, the solvent was removed. The residue was diluted with EtOAc (30 mL), and the organic phase was washed with water (25 mL×4), dried over sodium sulphate and evaporated in vacuo. The crude product was purified by column chromatography to give ethyl 3-[5-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-7-fluoro-1H-indol-2-yl]propanoate (D166) (600 mg) as a yellow solid. MS (ES): C23H22ClFN4O4 requires 472; found 473.2 (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 0.5 h
  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-87112ad933684c619f53f1bfe563b63d
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

Loading…