Cesium carbonate → HCID 67466579, compound

HRID 1045999Notes

Reaction equation

HRID 1045999 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[C:14](I)=[CH:13][N:12]=[CH:11][N:10]=2)[C:5]([F:16])=[CH:4][C:3]=1[NH2:17].[CH3:18][N:19]1[CH:23]=[C:22](B2OC(C)(C)C(C)(C)O2)[CH:21]=[N:20]1.C(=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>[F:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[C:14]([C:22]3[CH:21]=[N:20][N:19]([CH3:18])[CH:23]=3)=[CH:13][N:12]=[CH:11][N:10]=2)[C:5]([F:16])=[CH:4][C:3]=1[NH2:17]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 66339751HCID 66339751, compound

Product 1

HCID 67466579HCID 67466579, compoundYield 90.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a degassed solution of 2,5-difluoro-4-(5-iodopyrimidin-4-yloxy)benzenamine (0.23 g, 0.659 mmol) in DMF (5 mL) was added 1-methyl-pyrazole-4-boronic acid pinacol ester (0.206 g, 0.988 mmol), cesium carbonate (0.644 g, 1977 mmol) in water (2 mL) and Pd(PPh3)4 (0.076 g, 0.066 mmol) and the mixture was stirred at 80° C. under an argon atmosphere for 1 hour. Water was added and the solution was extracted with EtOAc (3×). The organics were washed with 5% aqueous lithium chloride solution and brine, and then dried over MgSO4. The organics were filtered and concentrated under reduced pressure. The residue was treated with small amount of EtOAc and Et2O. The solid was collected by filtration to obtain 2,5-difluoro-4-(5-(1-methyl-1H-pyrazol-4-yl)pyrimidin-4-yloxy)benzenamine (0.18 g, 90% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.02 (s, 1H), 8.54 (s, 1H), 8.30 (s, 1H), 8.09 (s, 1H), 7.21 (m, 1H), 6.69 (m, 1H), 5.42 (s, 2H), 3.89 (s, 3H); MS (ESI) m/z: 304.1 (M+H+).

Workup

  1. extractionthe solution was extracted with EtOAc (3×)
  2. washThe organics were washed with 5% aqueous lithium chloride solution and brine
  3. dry with materialdried over MgSO4
  4. filtrationThe organics were filtered
  5. concentrationconcentrated under reduced pressure
  6. additionThe residue was treated with small amount of EtOAc and Et2O
  7. filtrationThe solid was collected by filtration

Sources & evidence

ORD record
ord-cf6a71b1c90c49e3b56187c69269e915
Source dataset
uspto-grants-2013_10
Patent number
US08569319B2

Reaction notes

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