Cesium carbonate → 4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)benzenamine

HRID 1098544Notes

Reaction equation

HRID 1098544 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH2:15])=[CH:11][CH:10]=2)[CH:5]=[CH:4][N:3]=1.[N:16]1[N:17]=[CH:18][CH2:19][CH:20]=1.[C:21]([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:21][N:16]1[CH:20]=[C:19]([C:2]2[CH:7]=[C:6]([O:8][C:9]3[CH:14]=[CH:13][C:12]([NH2:15])=[CH:11][CH:10]=3)[CH:5]=[CH:4][N:3]=2)[CH:18]=[N:17]1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 120297994H-pyrazoleHCID 578334304-(2-Chloro-pyridin-4-yloxy)-phenylamine

Product 1

HCID 589169634-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)benzenamineYield 82.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

4-(2-Chloro-pyridin-4-yloxy)-phenylamine (0.7 g, 3.2 mmol), 1-methyl-4-(4,4,5,5-tetramethyl)-[1,3,2]dioxaborolan-2-yl)-4H-pyrazole (1.0 g, 4.8 mmol), Cs2CO3 (4.0 g, 12.3 mmol) and Pd(PPh3)4 (0.45 g, 0.4 mmol) were combined in a mixture of DMF and water (3:1, 20 mL). The reaction mixture was degassed, blanketed with argon and heated to 90° C. overnight. The reaction mixture was diluted with water and extracted with EtOAc (3×50 mL). The combined organics were washed with saturated brine, dried (MgSO4), concentrated in vacuo and purified by silica gel chromatography to provide 4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)benzenamine (0.7 g, 74% yield). 1H NMR (300 MHz, DMSO-d6), δ 8.29 (d, J=5.7 Hz, 1 H), 8.19 (s, 1 H), 7.90 (s, 1 H), 7.10 (d, J=2.4 Hz, 1 H), 6.83 (d, J=8.7 Hz, 2 H), 6.62 (d, J=8.7 Hz 2 H), 6.52 (dd, J=2.4, 5.7 Hz, 1 H), 5.10 (s, 2 H), 3.84 (s, 3 H); MS (ESI) m/z: 267.3 (M+H+)

Workup

  1. customThe reaction mixture was degassed
  2. additionThe reaction mixture was diluted with water
  3. extractionextracted with EtOAc (3×50 mL)
  4. washThe combined organics were washed with saturated brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-587ade711dfe409f965ed1d731dc6cc1
Source dataset
uspto-grants-2012_03
Patent number
US08143293B2

Reaction notes

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