Potassium Phosphate, Tribasic → 4-{4-(3-chloro-4-fluoro-phenyl)-6-[4-(3-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-pyrimidin-2-yl}-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

HRID 230947Notes

Reaction equation

HRID 230947 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:32]([O:36][C:37]([N:39]1[CH2:44][CH:43]=[C:42](B2OC(C)(C)C(C)(C)O2)[CH2:41][CH2:40]1)=[O:38])([CH3:35])([CH3:34])[CH3:33].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.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>[C:32]([O:36][C:37]([N:39]1[CH2:40][CH:41]=[C:42]([C:2]2[N:7]=[C:6]([C:8]3[CH:13]=[CH:12][C:11]([F:14])=[C:10]([Cl:15])[CH:9]=3)[CH:5]=[C:4]([N:16]3[CH2:21][CH2:20][N:19]([C:22]4[C:27]([C:28]([F:31])([F:29])[F:30])=[CH:26][CH:25]=[CH:24][N:23]=4)[CH2:18][CH2:17]3)[N:3]=2)[CH2:43][CH2:44]1)=[O:38])([CH3:35])([CH3:33])[CH3:34]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 577614902-Chloro-4-(3-chloro-4-fluoro-phenyl)-6-[4-(3-trifluoromethylpyridin-2-yl)-piperazin-1-yl]-pyrimidine

Product 1

HCID 577610754-{4-(3-chloro-4-fluoro-phenyl)-6-[4-(3-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-pyrimidin-2-yl}-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

Heat a solution of 2-chloro-4-(3-chloro-4-fluoro-phenyl)-6-[4-(3-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-pyrimidine (774 mg, 1.64 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (608 mg, 1.97 mmol (prepared essentially as described by Eastwood (2000) Tetrahedron Letters 41 (19):3705-3708), K3PO4 (2M, 1.64 mL) and Pd(PPh3)4 (76 mg, 0.07 mmol) in dioxane at 80° C. for 16 hours. Partition the reaction mixture between brine and EtOAc, dry the EtOAc layer (Na2SO4) and concentrate under reduced pressure. Flash chromatography (30% EtOAc in hexanes as eluent) yields 4-{4-(3-chloro-4-fluoro-phenyl)-6-[4-(3-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-pyrimidin-2-yl}-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester as a foam.

Workup

  1. customprepared essentially
  2. customPartition the reaction mixture between brine and EtOAc
  3. dry with materialdry the EtOAc layer (Na2SO4)
  4. concentrationconcentrate under reduced pressure

Sources & evidence

ORD record
ord-ed76598abb4342cdb68bb813bd48bd63
Source dataset
uspto-grants-2009_07
Patent number
US07566712B2

Reaction notes

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