Lithium Chloride → 5-(4-(benzyloxy)-3-fluorophenyl)-2-(4-fluorophenylamino)-3-methylpyrimidin-4(3H)-one

HRID 2241256Notes

Reaction equation

HRID 2241256 reaction equation
Br[C:2]1[C:3](=[O:17])[N:4]([CH3:16])[C:5]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=2)=[N:6][CH:7]=1.[CH2:18]([O:25][C:26]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28][C:27]=1[F:35])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[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>[CH2:18]([O:25][C:26]1[CH:31]=[CH:30][C:29]([C:2]2[C:3](=[O:17])[N:4]([CH3:16])[C:5]([NH:8][C:9]3[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=3)=[N:6][CH:7]=2)=[CH:28][C:27]=1[F:35])[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1

Participants

7

Reactant 3

HCID 433294Lithium ChlorideHCID 27377884-Benzyloxy-3-fluorophenylboronic AcidHCID 685151905-bromo-2-(4-fluorophenylamino)-3-methylpyrimidin-4(3H)-one

Product 1

HCID 685097675-(4-(benzyloxy)-3-fluorophenyl)-2-(4-fluorophenylamino)-3-methylpyrimidin-4(3H)-oneYield 76%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

A suspension of 5-bromo-2-(4-fluorophenylamino)-3-methylpyrimidin-4(3H)-one (0.130 g, 0.436 mmol), 4-(benzyloxy)-3-fluorophenylboronic acid (0.129 g, 0.523 mmol), Pd(PPh3)4 (0.025 g, 0.022 mmol) and lithium chloride (0.092 g, 2.18 mmol) in dioxane (1.5 mL) and 2 M aqueous Na2CO3 (1.5 mL) was stirred at 100° C. for 30 minutes. The reaction mixture was cooled to room temperature and then partitioned between EtOAc and H2O. The phases were separated, and the aqueous phase was re-extracted with EtOAc (1×). The combined organic layers were dried (Na2SO4), filtered and concentrated to yield a crude black solid. The crude product was purified by flash column chromatography, eluting with 10:1 dichloromethane/EtOAc. The desired product (0.139 g, 76%) was obtained as a grey-white solid.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. custompartitioned between EtOAc and H2O
  3. customThe phases were separated
  4. extractionthe aqueous phase was re-extracted with EtOAc (1×)
  5. dry with materialThe combined organic layers were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto yield a crude black solid
  9. customThe crude product was purified by flash column chromatography
  10. washeluting with 10:1 dichloromethane/EtOAc

Sources & evidence

ORD record
ord-56f6f8ec1a684317ab6ed0b3f5446e83
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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