1-Hydroxybenzotriazole → HCID 59146122, compound

HRID 1512766Notes

Reaction equation

HRID 1512766 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.O[NH:26]/[C:27](=[N:46]/[H])/[C:28]1[CH:29]=[CH:30][CH:31]=[C:32]2[C:36]=1[NH:35][CH:34]=[C:33]2[CH2:37][CH2:38][CH2:39][CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>O1CCCC1.C(Cl)CCl>[Cl:1][C:2]1[CH:3]=[C:4]([C:5]2[O:7][N:46]=[C:27]([C:28]3[CH:29]=[CH:30][CH:31]=[C:32]4[C:36]=3[NH:35][CH:34]=[C:33]4[CH2:37][CH2:38][CH2:39][CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42])[N:26]=2)[CH:8]=[CH:9][C:10]=1[O:11][CH:12]([CH3:14])[CH3:13]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 2724141Tetrabutylammonium FluorideHCID 225977283-Chloro-4-(propan-2-yloxy)benzoic acidHCID 178506491HCID 178506491, compound

Product 1

HCID 59146122HCID 59146122, compoundYield 19.4%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-chloro-4-[(1-methylethyl)oxy]benzoic acid (279 mg) in tetrahydrofuran (40 mL) stirred at room temp was added EDC (479 mg) and HOBT (363 mg). The reaction mixture was stirred at room temperature for 2 h. Then ethyl 5-{7-[(E)-(hydroxyamino)(imino)methyl]-1H-indol-3-yl}pentanoate (D55) (390 mg) was added. The reaction mixture was stirred at 60° C. for 1 h, and then TBAF (1.0 mol/L in THF, 5 mL) was added. The reaction solution was concentrated and transferred to a microwave vessel. The reaction vessel was sealed and heated in Biotage Initiator using initial normal to 145° C. for 3 h. After cooling the reaction, the solvent was removed and the residue was purified by Mass Directed AutoPrep to afford ethyl 5-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indol-3-yl]pentanoate (D56) (120 mg) as a yellow solid. δH (CDCl3, 400 MHz): 1.25 (3H, t), 1.45 (6H, d), 1.75-1.78 (4H, m), 2.37 (2H, t), 2.84 (2H, t), 4.14 (2H, q), 4.68-4.74 (1H, m), 7.05 (1H, d), 7.14-7.15 (1H, m), 7.25 (1H, t), 8.08 (1H, dd), 8.09 (1H, dd), 8.27 (1H, d), 9.58 (1H, s). MS (ES): C26H28ClN3O4 requires 481; found 482.2 (M+H+).

Workup

  1. stirringThe reaction mixture was stirred at 60° C. for 1 h
  2. concentrationThe reaction solution was concentrated
  3. customtransferred to a microwave vessel
  4. customThe reaction vessel was sealed
  5. temperatureheated in Biotage Initiator
  6. customnormal to 145° C.
  7. customfor 3 h
  8. temperatureAfter cooling
  9. customthe reaction
  10. customthe solvent was removed
  11. customthe residue was purified by Mass Directed AutoPrep

Sources & evidence

ORD record
ord-17200a5058174a83a0d72da96e0243f0
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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