Methyl 2,2-difluoro-2-(quinolin-6-yl)acetate → HCID 57690938, compound

HRID 40384Notes

Reaction equation

HRID 40384 reaction equation
Cl.[CH3:2][C:3]1[CH:7]=[C:6]([C:8]2[N:13]=[N:12][C:11]([NH:14][NH2:15])=[CH:10][CH:9]=2)[O:5][N:4]=1.[F:16][C:17]([F:32])([C:22]1[CH:23]=[C:24]2[C:29](=[CH:30][CH:31]=1)[N:28]=[CH:27][CH:26]=[CH:25]2)[C:18](OC)=O>Cl.CO>[F:32][C:17]([F:16])([C:18]1[N:12]2[N:13]=[C:8]([C:6]3[O:5][N:4]=[C:3]([CH3:2])[CH:7]=3)[CH:9]=[CH:10][C:11]2=[N:14][N:15]=1)[C:22]1[CH:23]=[C:24]2[C:29](=[CH:30][CH:31]=1)[N:28]=[CH:27][CH:26]=[CH:25]2

Participants

5

Reactant 2

HCID 58955252Methyl 2,2-difluoro-2-(quinolin-6-yl)acetateHCID 67502860HCID 67502860, compound

Product 1

HCID 57690938HCID 57690938, compound

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolvent

Conditions

Temperature
150 °C

Procedure

A suspension of 1-(6-(3-methylisoxazol-5-yl)pyridazin-3-yl)hydrazine hydrochloride (200 mg, 879 μmol) and methyl 2,2-difluoro-2-(quinolin-6-yl)acetate (208 mg, 879 μmol) in 5 M HCl (1 mL) was appropriately sealed and heated to 150° C. with microwaves for 4 h. The reaction was then quenched by a dropwise into cold 5 M NaOH (2 mL) and aqueous extracted with CHCl3/IPA (25 mL). The organic phase was then dried over MgSO4, concentrated, and purified with silica (40 g) eluting with 1>5% 2 M NH3 in MeOH/DCM. The product was then further purified on RP-HPLC eluting with water/ACN (0.1% TFA). Combined fractions concentrated, dissolved in DCM (5 mL) and MeOH (5 mL), then stirred with Si-Carbonate (0.5 g; 35 mmol) for 1 h. Si-Carbonate removed by filtration and filtrated concentrated with <0.5 mL remaining with product isolated by trituration. MS (ESI pos. ion) m/z: 379 (MH+). Calc'd exact mass for C19H12F2N6O: 378.

Workup

  1. customwas appropriately sealed
  2. customThe reaction was then quenched by a dropwise into cold 5 M NaOH (2 mL)
  3. extractionaqueous extracted with CHCl3/IPA (25 mL)
  4. dry with materialThe organic phase was then dried over MgSO4
  5. concentrationconcentrated
  6. custompurified with silica (40 g)
  7. washeluting with 1>5% 2 M NH3 in MeOH/DCM
  8. customThe product was then further purified on RP-HPLC
  9. washeluting with water/ACN (0.1% TFA)
  10. concentrationCombined fractions concentrated
  11. dissolutiondissolved in DCM (5 mL)
  12. customSi-Carbonate removed by filtration
  13. filtrationfiltrated
  14. concentrationconcentrated with <0.5 mL
  15. customisolated by trituration

Sources & evidence

ORD record
ord-90d53261ef874e4ea3ff93899bda5202
Source dataset
uspto-grants-2013_09
Patent number
US08524900B2

Reaction notes

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