Cesium carbonate → 1-(2,2-Diethoxyethyl)-N-(2-methoxy-5-nitrophenyl)-3-(pyridin-3-yl)-1H-pyrazole-5-amine

HRID 1055638Notes

Reaction equation

HRID 1055638 reaction equation
[CH2:1]([O:3][CH:4]([O:18][CH2:19][CH3:20])[CH2:5][N:6]1[C:10]([NH2:11])=[CH:9][C:8]([C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)=[N:7]1)[CH3:2].Br[C:22]1[CH:27]=[C:26]([N+:28]([O-:30])=[O:29])[CH:25]=[CH:24][C:23]=1[O:31][CH3:32].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([O:3][CH:4]([O:18][CH2:19][CH3:20])[CH2:5][N:6]1[C:10]([NH:11][C:24]2[CH:25]=[C:26]([N+:28]([O-:30])=[O:29])[CH:27]=[CH:22][C:23]=2[O:31][CH3:32])=[CH:9][C:8]([C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)=[N:7]1)[CH3:2]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 788702-Bromo-4-nitroanisoleHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 10516606HCID 10516606, compound

Product 1

HCID 896999171-(2,2-Diethoxyethyl)-N-(2-methoxy-5-nitrophenyl)-3-(pyridin-3-yl)-1H-pyrazole-5-amine

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

200 mg (0.72 mmol) of the compound of Example 4A together with 201 mg (0.87 mmol) of 2-bromo-4-nitroanisole were dissolved in 3.6 ml of dioxane, the mixture was degassed with argon and 16 mg (0.07 mmol) of palladium(II) acetate, 63 mg (0.11 mmol) of xantphos [4,5-bis(diphenylphosphino)-9,9-dimethylxanthene] and 589 mg (1.81 mmol) of caesium carbonate were added. The mixture was heated in a microwave oven (Biotage Initiator, with Dynamic Field Tuning) at 150° C. for 30 min. The reaction was then filtered through kieselguhr, the filtrate was concentrated under reduced pressure and the residue was separated by preparative HPLC (Method 12) into its components. The product-containing fractions were combined and, under reduced pressure, concentrated almost completely. The residue was made alkaline with a little saturated aqueous sodium bicarbonate solution. The precipitate formed was filtered off, washed with water and dried. This gave 210 mg (92% pure, 62% of theory) of the title compound.

Workup

  1. additionwere added
  2. filtrationThe reaction was then filtered through kieselguhr
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. customthe residue was separated by preparative HPLC (Method 12) into its components
  5. concentrationconcentrated almost completely
  6. customThe precipitate formed
  7. filtrationwas filtered off
  8. washwashed with water
  9. customdried

Sources & evidence

ORD record
ord-0c8b3f4cf02e4c1e88bfd04ebfe6bbb3
Source dataset
uspto-grants-2016_07
Patent number
US09394309B2

Reaction notes

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