Sodium Hydroxide → HCID 59596576, compound

HRID 2264969Notes

Reaction equation

HRID 2264969 reaction equation
[OH-].[Na+].C(O[C:6]([C:8]1[N:16]([CH3:17])[C:15]2[CH:14]=[CH:13][N:12]=[N:11][C:10]=2[C:9]=1[NH:18][C:19]1[CH:24]=[CH:23][C:22]([I:25])=[CH:21][C:20]=1[F:26])=[O:7])C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.CCN(C(C)C)C(C)C.[CH:57]([O:59][CH2:60][CH2:61][O:62][NH2:63])=[CH2:58]>C1COCC1>[CH:57]([O:59][CH2:60][CH2:61][O:62][NH:63][C:6]([C:8]1[N:16]([CH3:17])[C:15]2[CH:14]=[CH:13][N:12]=[N:11][C:10]=2[C:9]=1[NH:18][C:19]1[CH:24]=[CH:23][C:22]([I:25])=[CH:21][C:20]=1[F:26])=[O:7])=[CH2:58]

Participants

8

Reactant 6

HCID 14798Sodium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 21867017O-(2-(Vinyloxy)ethyl)hydroxylamineHCID 59596521HCID 59596521, compound

Product 1

HCID 59596576HCID 59596576, compoundYield 54.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

Sodium hydroxide (0.9 mL, 1M) was added to a suspension of 7-(2-fluoro-4-iodo-phenylamino)-5-methyl-5H-pyrrolo[3,2-c]pyridazine-6-carboxylic acid ethyl ester (242 mg, 0.55 mmol) in IMS (10 ml) and the reaction heated at 70° C. for 2 hours. The reaction mixture was concentrated in vacuo and the residue azeotroped with toluene (×3) to give a solid. The resultant crude solid was suspended in THF and HOBT (103 mg, 0.77 mmol), EDCI (136 mg, 0.69 mmol), DIPEA (0.144 ml, 0.83 mmol) and O-(2-vinyloxy-ethyl)-hydroxylamine (85 mg, 0.825 mmol) were then added and the reaction stirred at room temperature for 72 hours. The mixture was then concentrated in vacuo and the resultant residue dissolved in ethyl acetate (20 ml) and washed with water. The organic layer was separated, dried (Na2SO4), and filtered before concentrating in vacuo. The crude residue was purified by flash chromatography (Si-PPC, gradient 0-90% ethyl acetate in cyclohexane then 20% methanol in ethyl acetate) to yield the title compound as an orange solid (148 mg, 54%). LCMS (method B): RT=2.64 min, M+H+=498.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue azeotroped with toluene (×3)
  3. customto give a solid
  4. concentrationThe mixture was then concentrated in vacuo
  5. dissolutionthe resultant residue dissolved in ethyl acetate (20 ml)
  6. washwashed with water
  7. customThe organic layer was separated
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationbefore concentrating in vacuo
  11. customThe crude residue was purified by flash chromatography (Si-PPC, gradient 0-90% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-9f3b214287e04753ad833705cf4103bb
Source dataset
uspto-grants-2010_12
Patent number
US07855216B2

Reaction notes

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