Methyl iodide → HCID 86710615, compound

HRID 1027216Notes

Reaction equation

HRID 1027216 reaction equation
C(OC1C=C2C(C=CC(O)=C2)=CC=1C1N=NC(N(C)C2CC(C)(C)NC(C)(C)C2)=CC=1)C1C=CC=CC=1.[H-].[Na+].CI.[CH2:42]([O:49][C:50]1[C:51]([C:62]2[N:67]=[N:66][C:65]([N:68]([CH3:80])[CH:69]3[CH2:74][C:73]([CH3:76])([CH3:75])[N:72](C)[C:71]([CH3:79])([CH3:78])[CH2:70]3)=[CH:64][CH:63]=2)=[CH:52][C:53]2[C:58]([CH:59]=1)=[CH:57][C:56]([O:60][CH3:61])=[CH:55][CH:54]=2)[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1>CN(C=O)C>[CH2:42]([O:49][C:50]1[C:51]([C:62]2[N:67]=[N:66][C:65]([N:68]([CH3:80])[CH:69]3[CH2:74][C:73]([CH3:75])([CH3:76])[NH:72][C:71]([CH3:79])([CH3:78])[CH2:70]3)=[CH:64][CH:63]=2)=[CH:52][C:53]2[C:58]([CH:59]=1)=[CH:57][C:56]([O:60][CH3:61])=[CH:55][CH:54]=2)[C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1

Participants

6

Reactant 4

HCID 6328Methyl iodide2×HCID 24758Sodium hydrideHCID 86710616HCID 86710616, compoundHCID 136377150HCID 136377150, compound2×

Product 1

HCID 86710615HCID 86710615, compoundYield 80%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a reaction mixture of 7-(benzyloxy)-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalen-2-ol (Intermediate 5-1, 500 mg, 1.01 mmol) in DMF (3 mL) was added 60% wt NaH (48.3 mg, 1.21 mmol) at 0° C. The mixture was stirred for 0.5 h, then methyl iodide (0.063 mL, 1.01 mmol) was added. The mixture was stirred at RT for 1.5 hours, then another portion of methyl iodide (0.063 mL, 1.01 mmol) was added. The reaction mixture was stirred at RT overnight, then slowly quenched with water. The residue was partitioned between water and DCM, and the aqueous layer was further extracted with DCM. The combined organic layers were dried over Na2SO4, and concentrated in vacuo. The residue was purified via silica gel flash column chromatography (0-20% 1.5 M NH3 in MeOH/DCM) to give a mixture of Intermediate 5-4 and 6-(3-(benzyloxy)-6-methoxynaphthalen-2-yl)-N-methyl-N-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyridazin-3-amine which was used without further purification (412 mg, 80% yield). MS (M+1)=511.5.

Workup

  1. stirringThe mixture was stirred at RT for 1.5 hours
  2. stirringThe reaction mixture was stirred at RT overnight
  3. customslowly quenched with water
  4. customThe residue was partitioned between water and DCM
  5. extractionthe aqueous layer was further extracted with DCM
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified via silica gel flash column chromatography (0-20% 1.5 M NH3 in MeOH/DCM)
  9. customto give
  10. customwas used without further purification (412 mg, 80% yield)

Sources & evidence

ORD record
ord-e1382f7392b44c1680d16524bcd076d4
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

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