Cesium fluoride → 4-Methoxy-2-(1-methyl-1H-pyrazol-4-yl)pyrimidin-5-amine

HRID 2205922Notes

Reaction equation

HRID 2205922 reaction equation
Cl[C:2]1[N:7]=[C:6]([O:8][CH3:9])[C:5]([NH2:10])=[CH:4][N:3]=1.[CH3:11][N:12]1[CH:16]=[C:15](B2OC(C)(C)C(C)(C)O2)[CH:14]=[N:13]1.[F-].[Cs+]>COCCOC.CO.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>[CH3:9][O:8][C:6]1[C:5]([NH2:10])=[CH:4][N:3]=[C:2]([C:15]2[CH:14]=[N:13][N:12]([CH3:11])[CH:16]=2)[N:7]=1

Participants

7

Reactant 3

HCID 25953Cesium fluorideHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 211863562-Chloro-4-methoxypyrimidin-5-amine

Product 1

HCID 682911184-Methoxy-2-(1-methyl-1H-pyrazol-4-yl)pyrimidin-5-amineYield 93%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 86595564Dimethoxyethane methanolSolvent

Conditions

Temperature
150 °C

Procedure

Tetrakis(triphenylphosphine)palladium (30 mg, 0.026 mmol) was added to a solution of 2-chloro-4-methoxypyrimidin-5-amine (41 mg, 0.257 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (107 mg, 0.514 mmol) and cesium fluoride (117 mg, 0.771 mmol) in DME/MeOH (2/1, 1.6 mL). The reaction mixture was heated under microwave irradiation at 150° C. for 10 minutes. The reaction was then diluted with EtOAc and quenched with water. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were dried (Na2SO4), filtered and concentrated under reduced pressure. The crude mixture was purified via Biotage silica gel column chromatography eluting with DCM/EtOH 99/1 to 90/10 followed by filtration through a SCX-2 column to afford the title product as a white solid (49 mg, 93%). 1H NMR (500 MHz, CDCl3): δ 3.68 (br s, 2H), 3.93 (s, 3H), 4.06 (s, 3H), 7.88 (s, 1H), 7.92 (s, 1H), 8.04 (s, 1H). LC (Method B)-MS (ESI, m/z) tR 1.33 min, 206 [M+H]+

Workup

  1. customquenched with water
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with EtOAc
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude mixture was purified via Biotage silica gel column chromatography
  8. washeluting with DCM/EtOH 99/1 to 90/10
  9. filtrationfollowed by filtration through a SCX-2 column

Sources & evidence

ORD record
ord-9ffd82174dc1473cae9d58f9b3f065d8
Source dataset
uspto-grants-2016_06
Patent number
US09371319B2

Reaction notes

Loading…