Cesium carbonate → N-(6-Methoxy-pyridazin-3-yl)-2,2-dimethyl-propionamide

HRID 226108

Reaction equation

HRID 226108 reaction equation
Cl[C:2]1[N:3]=[N:4][C:5]([O:8][CH3:9])=[CH:6][CH:7]=1.[CH3:10][C:11]([CH3:16])([CH3:15])[C:12]([NH2:14])=[O:13].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:9][O:8][C:5]1[N:4]=[N:3][C:2]([NH:14][C:12](=[O:13])[C:11]([CH3:16])([CH3:15])[CH3:10])=[CH:7][CH:6]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 12957TrimethylacetamideHCID 744033-Chloro-6-methoxypyridazineHCID 634876Binap, (A+-)-

Product 1

HCID 68840920N-(6-Methoxy-pyridazin-3-yl)-2,2-dimethyl-propionamideYield 175.2%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

3-Chloro-6-methoxy-pyridazine (10.0 g, 69. 18 mmol) is mixed with 2,2-dimethyl-propionamide (8.40 g, 83.01 mmol), BINAP (2.15 g, 3.46 mmol), Cs2CO3 (33.8 g, 103.8 mmol) in dioxane (150 mL). It is degassed by passing N2 through for 10 min at rt. Pd2(dba)3 (3.16 g, 3.46 mmol) is then added and the resulting reaction is refluxed overnight. The reaction is cooled to rt, diluted with EtOAc (150 mL); filtered through silica gel; washed with EtOAc (2×150 mL). The filtrate is washed with H2O (2×300 mL); dried with MgSO4; filtered and concentrated. Purification of the crude material by chromatography gives the title compound (6.59 g, 31.53 mmol, 46%). 1H NMR (CDCl3): δ. 1.35 (s, 9H), 4.08 (s, 3H), 7.01 (d, J=9.7 Hz, 1H), 8.41 (d, J=9.7 Hz, 1H), 8.44 (bs, 1H) ppm. ES-MS (m/z): calcd for C10H15N3O2 (M+H)+: 210.3. found: 210.1.

Workup

  1. customIt is degassed
  2. customthrough for 10 min
  3. customat rt
  4. customthe resulting reaction
  5. temperatureis refluxed overnight
  6. filtrationfiltered through silica gel
  7. washwashed with EtOAc (2×150 mL)
  8. washThe filtrate is washed with H2O (2×300 mL)
  9. dry with materialdried with MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customPurification of the crude material by chromatography

Sources & evidence

ORD record
ord-d7cb36f3b524427992584efaf5ffbc39
Source dataset
uspto-grants-2009_07
Patent number
US07557103B2

Linked notes

Loading…