Cesium carbonate → HCID 59233383, compound

HRID 1400087Notes

Reaction equation

HRID 1400087 reaction equation
Br[C:2]1[N:3]=[N:4][C:5]([C:10]([F:13])([F:12])[F:11])=[CH:6][C:7]=1[O:8][CH3:9].[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][CH:24]([NH2:27])[CH2:23][CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15].C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][CH:24]([NH:27][C:2]2[N:3]=[N:4][C:5]([C:10]([F:13])([F:12])[F:11])=[CH:6][C:7]=2[O:8][CH3:9])[CH2:23][CH2:22]1)=[O:20])([CH3:17])([CH3:15])[CH3:16]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 12682914-Amino-1-Boc-piperidineHCID 592333823-Bromo-4-methoxy-6-(trifluoromethyl)pyridazine

Product 1

HCID 59233383HCID 59233383, compoundYield 63.2%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

To a stirred solution of 3-bromo-4-methoxy-6-trifluoromethyl-pyridazine (D6) (0.79 g, 3.07 mmol), 4-amino-piperidine-1-carboxylic acid tert-butyl ester (0.74 g, 3.69 mmol) and cesium carbonate (2.0 g, 6.14 mmol) in toluene (15 ml) in a sealed tube under nitrogen, were added (R)-(+)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.29 g, 0.46 mmol) and palladium(II) acetate (0.034 g, 0.15 mmol). The reactiom mixture was stirred at 110° C. for 18 h. After cooling to room temperature, the reaction mixture was filtered though Celite and the filtrate was evaporated. The crude product was purified by flash column chromatography (silica gel; 3% ammonia in methanol (7M)/dichloromethane). The desired fractions were collected and evaporated in vacuo. to yield D7 (0.73 g, 63%) as a yellow solid. C16H23F3N4O3 requires 376; Found 377 (MH+).

Workup

  1. temperatureAfter cooling to room temperature
  2. filtrationthe reaction mixture was filtered though Celite
  3. customthe filtrate was evaporated
  4. customThe crude product was purified by flash column chromatography (silica gel; 3% ammonia in methanol (7M)/dichloromethane)
  5. customThe desired fractions were collected
  6. customevaporated in vacuo

Sources & evidence

ORD record
ord-7df0ef6da96c4be39665fc50b5f4f2ba
Source dataset
uspto-grants-2014_12
Patent number
US08906921B2

Reaction notes

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