Hydrochloric Acid → 5-(5-{3-Chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indazole

HRID 2189734Notes

Reaction equation

HRID 2189734 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.CCN=C=NCCCN(C)C.Cl.Cl.C1C=CC2N(O)N=NC=2C=1.O[NH:39][C:40]([C:42]1[CH:43]=[C:44]2[C:48](=[CH:49][CH:50]=1)[NH:47][N:46]=[CH:45]2)=[NH:41]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:5]2[O:7][N:39]=[C:40]([C:42]3[CH:43]=[C:44]4[C:48](=[CH:49][CH:50]=3)[NH:47][N:46]=[CH:45]4)[N:41]=2)[CH:8]=[CH:9][C:10]=1[O:11][CH:12]([CH3:14])[CH3:13]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 225977283-Chloro-4-(propan-2-yloxy)benzoic acidHCID 178513242HCID 178513242, compound

Product 1

HCID 532392355-(5-{3-Chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indazoleYield 34.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-chloro-4-[(1-methylethyl)oxy]benzoic acid (D3) (712 mg), EDCl.HCl (699 mg) and HOBT (493 mg) were dissolved in DMF (16.5 ml) and stirred at RT for 10 minutes. N-hydroxy-1H-indazole-5-carboximidamide (D2) (584 mg) was added and the mixture heated to 80° C. for 12 hours. The reaction mixture was then cooled to RT and left to stand for the weekend, evaporated to dryness and re-dissolved in H2O. This solution was extracted with EtOAc (×3) and the combined extracts washed with brine, evaporated and triturated with DCM twice, sonicated for 4 mins before filtering, drying and repeating once to give the title compound (407 mg) as a pink solid. δH (d6-DMSO, 400 MHz): 1.37 (6H, d), 4.89 (1H, septet), 7.46 (1H, d), 7.73 (1H, d), 8.04 (1H, d), 8.13 (1H, d), 8.20 (1H, s), 8.28 (1H, s), 8.58 (1H, s). MS (ES): C18H15ClN4O2 requires 354; found 355 (M+H).

Workup

  1. temperaturethe mixture heated to 80° C. for 12 hours
  2. temperatureThe reaction mixture was then cooled to RT
  3. waitleft
  4. customevaporated to dryness
  5. dissolutionre-dissolved in H2O
  6. extractionThis solution was extracted with EtOAc (×3)
  7. washthe combined extracts washed with brine
  8. customevaporated
  9. customtriturated with DCM twice
  10. customsonicated for 4 mins
  11. filtrationbefore filtering
  12. customdrying

Sources & evidence

ORD record
ord-abba82b1d9d24c09bb6948872cd45c2e
Source dataset
uspto-grants-2012_12
Patent number
US08324254B2

Reaction notes

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