Methyl iodide → HCID 86686141, compound

HRID 869192Notes

Reaction equation

HRID 869192 reaction equation
[C:1]([O:5][C:6]([N:8]([CH2:26][C:27]1([C:31]2[C:36]([F:37])=[CH:35][CH:34]=[CH:33][N:32]=2)[CH2:30][CH2:29][CH2:28]1)[C:9]1[N:14]=[N:13][C:12]([CH:15]2[N:19]=[C:18]([OH:20])[CH:17]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[S:16]2)=[CH:11][CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:38]I.[H-].[Na+]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]([CH2:26][C:27]1([C:31]2[C:36]([F:37])=[CH:35][CH:34]=[CH:33][N:32]=2)[CH2:30][CH2:29][CH2:28]1)[C:9]1[N:14]=[N:13][C:12]([CH:15]2[N:19]=[C:18]([O:20][CH3:38])[CH:17]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[S:16]2)=[CH:11][CH:10]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 178470551HCID 178470551, compound

Product 1

HCID 86686141HCID 86686141, compoundYield 53.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

To a stirring solution of ethyl 2-(6-(t-butoxycarbonyl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)amino)pyridazin-3-yl)-4-hydroxy-2,5-dihydrothiazole-5-carboxylate (350 mg, 0.7 mmol) in DMF (4 mL) was added methyl iodide (200 μL, 3.3 mmol) and sodium hydride (60% dispersion in mineral oil, 40 mg, 1 mmol). The reaction was stirred at rt for 1 h and at 40° C. for 45 min. The reaction was then concentrated and quenched with water (5 mL), poured into ethyl acetate (150 mL), and washed with 0.1M HCl (50 mL, aq) and brine (50 mL). The organic layer was separated, dried over Na2SO4, filtered, concentrated and purified by silica gel column chromatography (EtOAC/hexanes) to afford 205 mg of ethyl 2-(6-(tert-butoxycarbonyl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)amino)pyridazin-3-yl)-4-methoxy-2,5-dihydrothiazole-5-carboxylate. This compound was dissolved in methanol (4 mL) and 1M KOH (aq, 2 mL). The reaction mixture was heated to 75° C. and stirred for 45 min. The reaction was cooled and the pH was adjusted to 4 using 1M HCl. The reaction was then poured into ethyl acetate (50 mL), washed with brine (15 mL), dried over Na2SO4, filtered, and concentrated to give 175 mg of 2-(6-(t-butoxycarbonyl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)amino)pyridazin-3-yl)-4-methoxy-2,5-dihydrothiazole-5-carboxylic acid as a white foam.

Workup

  1. concentrationThe reaction was then concentrated
  2. customquenched with water (5 mL)
  3. additionpoured into ethyl acetate (150 mL)
  4. washwashed with 0.1M HCl (50 mL, aq) and brine (50 mL)
  5. customThe organic layer was separated
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custompurified by silica gel column chromatography (EtOAC/hexanes)

Sources & evidence

ORD record
ord-c6b2dd18dafd452c98db0f7243ca16d3
Source dataset
uspto-grants-2015_03
Patent number
US08969346B2

Reaction notes

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