Cesium carbonate → HCID 59233381, compound

HRID 1400081Notes

Reaction equation

HRID 1400081 reaction equation
Cl[C:2]1[N:3]=[N:4][C:5]([Cl:10])=[CH:6][C:7]=1[O:8][CH3:9].[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][CH:21]([NH2:24])[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].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:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][CH:21]([NH:24][C:2]2[N:3]=[N:4][C:5]([Cl:10])=[CH:6][C:7]=2[O:8][CH3:9])[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:12])[CH3:13]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 12682914-Amino-1-Boc-piperidineHCID 64013433,6-dichloro-4-methoxypyridazine

Product 1

HCID 59233381HCID 59233381, compoundYield 32%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

To a stirred solution of 3,6-dichloro-4-methoxy-pyridazine (0.73 g, 4.08 mmol) (prepared by a procedure similar to that described in Eichenberger, K.; Rometsch, R.; Druey, J. Australian Journal of Chemistry 1956, 9, 1755-1764), 4-amino-piperidine-1-carboxylic acid tert-butyl ester (0.98 g, 4.90 mmol) and cesium carbonate (2.66 g, 8.16 mmol) in toluene (15 ml) in a sealed tube under nitrogen, were added (R)-(+)-2,2′-bis (diphenylphosphino)-1,1′-binaphthyl (0.38 g, 0.61 mmol) and palladium(II) acetate (0.046 g, 0.20 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 D1 (0.44 g, 32%) as a yellow solid. C15H23ClN4O3 requires 342; Found 343 (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-ded7f4e1861c473d85b04987eb868ac4
Source dataset
uspto-grants-2014_12
Patent number
US08906921B2

Reaction notes

Loading…