Cesium carbonate → 1-{4-(3-Chloro-4-fluoro-phenyl)-6-[4-(3-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-pyrimidin-2-yl}-4-propyl-piperazin-2-one

HRID 230949Notes

Reaction equation

HRID 230949 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[C:10]([Cl:15])[CH:9]=2)[CH:5]=[C:4]([N:16]2[CH2:21][CH2:20][N:19]([C:22]3[C:27]([C:28]([F:31])([F:30])[F:29])=[CH:26][CH:25]=[CH:24][N:23]=3)[CH2:18][CH2:17]2)[N:3]=1.C(O[C:37]([N:39]1[CH2:44][CH2:43][NH:42][C:41](=[O:45])[CH2:40]1)=O)(C)(C)C.C([O-])([O-])=O.[Cs+].[Cs+].[C:52]1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=C[CH:53]=1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:15][C:10]1[CH:9]=[C:8]([C:6]2[CH:5]=[C:4]([N:16]3[CH2:17][CH2:18][N:19]([C:22]4[C:27]([C:28]([F:30])([F:29])[F:31])=[CH:26][CH:25]=[CH:24][N:23]=4)[CH2:20][CH2:21]3)[N:3]=[C:2]([N:42]3[CH2:43][CH2:44][N:39]([CH2:37][CH2:52][CH3:53])[CH2:40][C:41]3=[O:45])[N:7]=2)[CH:13]=[CH:12][C:11]=1[F:14]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 3157178Tert-butyl 3-oxopiperazine-1-carboxylateHCID 577614902-Chloro-4-(3-chloro-4-fluoro-phenyl)-6-[4-(3-trifluoromethylpyridin-2-yl)-piperazin-1-yl]-pyrimidine

Product 1

HCID 577616391-{4-(3-Chloro-4-fluoro-phenyl)-6-[4-(3-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-pyrimidin-2-yl}-4-propyl-piperazin-2-one

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 2-chloro-4-(3-chloro-4-fluoro-phenyl)-6-[4-(3-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-pyrimidine (259 mg, 0.55 mmol), 3-oxo-piperazine-1-carboxylic acid tert-butyl ester (prepared essentially as described by Kane and Carr (1980) Teit. Lett. 21:3019-20; 132 mg, 0.66 mmol) and Cs2CO3 (250 mg, 0.77 mmol) in dioxane, add 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (19 mg, 0.03 mmol). Purge the reaction mixture for 10 minutes with nitrogen gas and then add Pd2(dba)3 (10 mg, 0.011 mmol). After purging with nitrogen gas for an additional 5 minutes, heat the mixture at 90° C. for 16 hours under nitrogen atmosphere. Filter the mixture through celite and concentrate under reduced pressure to give the title compound.

Workup

  1. customPurge the reaction mixture for 10 minutes with nitrogen gas
  2. customAfter purging with nitrogen gas for an additional 5 minutes
  3. filtrationFilter the mixture through celite and
  4. concentrationconcentrate under reduced pressure

Sources & evidence

ORD record
ord-a19edf61d7dc49f98e32f7742fc042b7
Source dataset
uspto-grants-2009_07
Patent number
US07566712B2

Reaction notes

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