Cesium carbonate → HCID 46222817, compound

HRID 1907813Notes

Reaction equation

HRID 1907813 reaction equation
C([C:5]1[CH:19]=[CH:18][CH:17]=[CH:16][C:6]=1[C:7]([NH:9][CH:10]1[CH2:15][CH2:14][CH2:13][NH:12][CH2:11]1)=[O:8])(C)(C)C.Cl[C:21]1[CH:22]=[C:23]([NH:29][C:30]2[CH:34]=[C:33]([CH3:35])[N:32]([CH3:36])[N:31]=2)[C:24](=[O:28])[N:25]([CH3:27])[N:26]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)[C:50]2C=CC3[C:52](=CC=CC=3)[C:51]=2[C:60]2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl.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].O1CCOCC1>[C:51]([C:18]1[CH:19]=[CH:5][C:6]([C:7]([NH:9][C@@H:10]2[CH2:15][CH2:14][CH2:13][N:12]([C:21]3[CH:22]=[C:23]([NH:29][C:30]4[CH:34]=[C:33]([CH3:35])[N:32]([CH3:36])[N:31]=4)[C:24](=[O:28])[N:25]([CH3:27])[N:26]=3)[CH2:11]2)=[O:8])=[CH:16][CH:17]=1)([CH3:60])([CH3:52])[CH3:50]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 585400026-chloro-4-(1,5-dimethyl-1H-pyrazol-3-ylamino)-2-methylpyridazin-3(2H)-oneHCID 67416702HCID 67416702, compound

Product 1

HCID 46222817HCID 46222817, compoundYield 325%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A 100-mL pressure flask is equipped with a magnetic stirrer was charged with tert-butyl-N-(piperidin-3-yl)benzamide (130 mg, 0.5 mmol), dioxane (10 mL), 6-chloro-4(1,5-dimethyl-1H-pyrazol-3-ylamino)-2-methylpyridazin-3(2H)-one (127 mg, 0.5 mmol), and cesium carbonate (326 mg, 1 mmol). Argon is bubbled through the solution whilst sonicating for 15 min. Tris(dibenzylideneacetone)dipalladium (0) (46 mg, 0.05 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (66 mg, 0.1 mmol) were then added, the flask was sealed and heated to 120° C. for 8 h. The resulting mixture was diluted with dichloromethane (300 mL) and washed with water (120 mL) filtered through a pad of celite, concentrated and purified by flash chromatography on silica gel to afford a 65% yield of (R)-4-tert-butyl-N-(1-(5-(1,5-dimethyl-1H-pyrazol-3-ylamino)-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)piperidin-3-yl)benzamide as a white solid (155 mg, 0.325 mmol).

Workup

  1. customA 100-mL pressure flask is equipped with a magnetic stirrer
  2. customArgon is bubbled through the solution
  3. customwhilst sonicating for 15 min
  4. customthe flask was sealed
  5. washwashed with water (120 mL)
  6. filtrationfiltered through a pad of celite
  7. concentrationconcentrated
  8. custompurified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-17a8fdbbb64642f18900f68bcd78b5b4
Source dataset
uspto-grants-2013_12
Patent number
US08598174B2

Reaction notes

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