Lithium Chloride → 5-(2,5-difluoro-4-methoxyphenyl)-3-methyl-2-(phenylamino)pyrimidin-4(3H)-one

HRID 1676378Notes

Reaction equation

HRID 1676378 reaction equation
Br[C:2]1[C:3](=[O:16])[N:4]([CH3:15])[C:5]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[N:6][CH:7]=1.[F:17][C:18]1[CH:23]=[C:22]([O:24][CH3:25])[C:21]([F:26])=[CH:20][C:19]=1B(O)O.[Cl-].[Li+]>O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+].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:17][C:18]1[CH:23]=[C:22]([O:24][CH3:25])[C:21]([F:26])=[CH:20][C:19]=1[C:2]1[C:3](=[O:16])[N:4]([CH3:15])[C:5]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[N:6][CH:7]=1

Participants

7

Reactant 3

HCID 433294Lithium ChlorideHCID 36965512,5-Difluoro-4-methoxyphenylboronic acidHCID 673454265-bromo-3-methyl-2-(phenylamino)pyrimidin-4(3H)-one

Product 1

HCID 673475135-(2,5-difluoro-4-methoxyphenyl)-3-methyl-2-(phenylamino)pyrimidin-4(3H)-one

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 10340Sodium CarbonateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of 5-bromo-3-methyl-2-(phenylamino)pyrimidin-4(3H)-one (Example 143, Step C, 0.100 g, 0.357 mmol), 2,5-difluoro-4-methoxyphenylboronic acid (0.081 g, 0.428 mmol), Pd(PPh3)4 (0.021 g, 0.018 mmol) and lithium chloride (0.076 g, 1.78 mmol) in dioxane (2 mL) and 2M aqueous Na2CO3 (2 mL) was stirred at 100° C. for 15 minutes. The reaction mixture was cooled to room temperature and then partitioned between EtOAc and H2O. The layers were separated and the aqueous layer was re-extracted with EtOAc (1×). The combined organic layers were dried over Na2SO4, filtered and concentrated. The crude product was purified by flash column chromatography, eluting with 5:1 CH2Cl2/EtOAc. The product was obtained (77 mg; 63%) as a grey-white solid. 1H NMR (400 MHz, DMSO-d6) δ 8.95 (br s, 1H), 7.74 (s, 1H), 7.55-7.49 (m, 2H), 7.39-7.28 (m, 3H), 7.18-7.13 (m, 2H), 3.86 (s, 3H), 3.54 (s, 3H). LRMS (ESI pos) m/e 344 (M+1).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. custompartitioned between EtOAc and H2O
  3. customThe layers were separated
  4. extractionthe aqueous layer was re-extracted with EtOAc (1×)
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by flash column chromatography
  9. washeluting with 5:1 CH2Cl2/EtOAc
  10. customThe product was obtained (77 mg; 63%) as a grey-white solid

Sources & evidence

ORD record
ord-16df0cdc644e4b5389cb9b1ec79e6f4d
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

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