Water → 3-methyl-4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)benzenamine

HRID 2060665Notes

Reaction equation

HRID 2060665 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][C:10]=2[CH3:16])[CH:5]=[CH:4][N:3]=1.[N:17]1[N:18]=[CH:19][CH2:20][CH:21]=1.[C:22]([O-])([O-])=O.[Cs+].[Cs+].O>CN(C=O)C.CCOC(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>[CH3:16][C:10]1[CH:11]=[C:12]([NH2:15])[CH:13]=[CH:14][C:9]=1[O:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([C:20]2[CH:21]=[N:17][N:18]([CH3:22])[CH:19]=2)[CH:7]=1

Participants

8

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 120297994H-pyrazoleHCID 866196714-(2-Chloropyridin-4-yloxy)-3-methylbenzenamine

Product 1

HCID 672540383-methyl-4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)benzenamineYield 88.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A solution of 4-(2-chloropyridin-4-yloxy)-3-methylbenzenamine (595 mg, 2.54 mmol), 1-methyl-4-(4,4,5,5-tetramethyl)-[1,3,2]dioxaborolan-2-yl)-4H-pyrazole (790 mg, 3.80 mmol) and Cs2CO3 (2.53 g, 7.77 mmol) in 10 mL of DMF (10 mL)/water (3 mL) was de-gassed under vacuum and blanketed with nitrogen. Pd(PPh3)4 (295 mg, 0.26 mmol) was added and the reaction mixture was heated to 90° C. overnight. The reaction mixture was diluted with EtOAc (30 mL) and washed with water (2×10 mL) and brine (2×10 mL). The aqueous portion was extracted with EtOAc (2×15 mL) and the combined organics were washed with brine (10 mL), concentrated in vacuo and purified on silica gel to provide 3-methyl-4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)benzenamine as a pale yellow foam (627 mg, 88% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.27 (d, J=6.0 Hz, 1H), 8.18 (s, 1H), 7.90 (d, J=0.7 Hz, 1H), 7.07 (d, J=2.2 Hz, 1H), 6.74 (d, J=8.6 Hz, 1H), 6.49 (d, J=2.5 Hz, 1H), 6.46-6.40 (m, 2H), 5.02 (s, 2H), 3.84 (s, 3H), 1.94 (s, 3H); MS (ESI) m/z: 281.2 (M+H+).

Workup

  1. washwashed with water (2×10 mL) and brine (2×10 mL)
  2. extractionThe aqueous portion was extracted with EtOAc (2×15 mL)
  3. washthe combined organics were washed with brine (10 mL)
  4. concentrationconcentrated in vacuo
  5. custompurified on silica gel

Sources & evidence

ORD record
ord-c66ce28bdbc5401395998d537d66d8b1
Source dataset
uspto-grants-2012_10
Patent number
US08278331B2

Reaction notes

Loading…