1-Hydroxybenzotriazole → HCID 66849985, compound

HRID 1846937Notes

Reaction equation

HRID 1846937 reaction equation
[F:1][C:2]([F:8])([F:7])[CH2:3][C:4](O)=[O:5].C1C=CC2N(O)N=NC=2C=1.[NH:19]([C:21]1[N:22]=[N:23][C:24]([C:27]2[CH:32]=[CH:31][C:30]([O:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)=[CH:29][CH:28]=2)=[CH:25][CH:26]=1)[NH2:20].CCOP(O)N(C(C)C)C(C)C>C(Cl)Cl.C1(N=C=NC2CCCCC2)CCCCC1.CCN=C=NCCCN(C)C.Cl.CO.C([O-])(O)=O.[Na+]>[F:1][C:2]([F:8])([F:7])[CH2:3][C:4]([NH:20][NH:19][C:21]1[N:22]=[N:23][C:24]([C:27]2[CH:32]=[CH:31][C:30]([O:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)=[CH:29][CH:28]=2)=[CH:25][CH:26]=1)=[O:5]

Participants

10

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 1954513'-O-ethyl-N,N-diisopropylphosphoramiditeHCID 27779723,3,3-Trifluoropropionic acidHCID 10265556HCID 10265556, compound

Product 1

HCID 66849985HCID 66849985, compound

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent3×HCID 10868DicyclohexylcarbodiimideSolventHCID 516892Sodium BicarbonateSolventHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideSolvent2×

Procedure

To a solution of 3,3,3-trifluoropropionic acid (2.07 mmole) in DCM (10 mL), was added EDCI HCl (3.02 mmole) and HOBt (2.07 mmole). The solution was stirred at RT for 0.5 hour followed by addition of 3-hydrazinyl-6-(4-phenoxyphenyl)pyridazine A, prepared as disclosed in Example 3, (2.07 mmole) in 30 mL of DCM and EDIPA ((7.24 mmole). The coupling reaction will also work with 1,3-dicyclohexylcarbodiimide and DCM as a solvent or EDCI HCl and methanol as a solvent. The resulting reaction mixture was stirred at RT overnight. The mixture was diluted with saturated aqueous NaHCO3. The organic extract was washed with H2O and dried over Na2SO4 and then evaporated in vacuo. The crude product was purified with prep TLC eluting with 5% methanol and dichloromethane mixture to give B.

Workup

  1. customprepared
  2. customThe coupling reaction
  3. customThe resulting reaction mixture
  4. stirringwas stirred at RT overnight
  5. extractionThe organic extract
  6. washwas washed with H2O
  7. dry with materialdried over Na2SO4
  8. customevaporated in vacuo
  9. customThe crude product was purified with prep TLC
  10. washeluting with 5% methanol and dichloromethane mixture
  11. customto give B

Sources & evidence

ORD record
ord-3f113ad60b654ebe928d893e8e2816f1
Source dataset
uspto-grants-2015_02
Patent number
US08952034B2

Reaction notes

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