Potassium Acetate → [5-(2-Fluoro-6-trifluoromethyl-pyridin-4-yl)imidazo[1,2-a]pyrazin-8-yl]-(4-morpholin-4-yl-phenyl)carbamic acid tert-butyl ester

HRID 1924934Notes

Reaction equation

HRID 1924934 reaction equation
[C:1]([O:5][C:6](=[O:30])[N:7]([C:20]1[C:21]2[N:22]([CH:27]=[CH:28][N:29]=2)[C:23](Br)=[CH:24][N:25]=1)[C:8]1[CH:13]=[CH:12][C:11]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)=[CH:10][CH:9]=1)([CH3:4])([CH3:3])[CH3:2].[F:31][C:32]1[CH:37]=[C:36](B2OC(C)(C)C(C)(C)O2)[CH:35]=[C:34]([C:47]([F:50])([F:49])[F:48])[N:33]=1.CC([O-])=O.[K+]>O1CCOCC1>[C:1]([O:5][C:6](=[O:30])[N:7]([C:20]1[C:21]2[N:22]([CH:27]=[CH:28][N:29]=2)[C:23]([C:36]2[CH:35]=[C:34]([C:47]([F:48])([F:49])[F:50])[N:33]=[C:32]([F:31])[CH:37]=2)=[CH:24][N:25]=1)[C:8]1[CH:13]=[CH:12][C:11]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)=[CH:10][CH:9]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 517044Potassium AcetateHCID 534170432-Fluoro-6-(trifluoromethyl)pyridine-4-boronic acid pinacol esterHCID 86616748(5-Bromoimidazo[1,2-a]pyrazin-8-yl)-(4-morpholin-4-ylphenyl)carbamic acid tert-butyl ester

Product 1

HCID 58228824[5-(2-Fluoro-6-trifluoromethyl-pyridin-4-yl)imidazo[1,2-a]pyrazin-8-yl]-(4-morpholin-4-yl-phenyl)carbamic acid tert-butyl esterYield 151.4%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

(5-Bromoimidazo[1,2-a]pyrazin-8-yl)-(4-morpholin-4-ylphenyl)carbamic acid tert-butyl ester (50 mg, 0.11 mmol), 2-fluoro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-6-(trifluoromethyl)pyridine (126 mg, 0.21 mmol), KOAc (31 mg, 0.32 mmol) and Pd(dppf)Cl2DCM (4.3 mg, 0.0053 mmol) are stirred under N2 in dioxane (0.3 mL) and heated at 85° C. for 2.5 h. The mixture is cooled and partitioned between NaHCO3 (5% aq., 5 mL) and EtOAc (15 mL). The layers are separated and the aqueous phase extracted with further EtOAc (2×10 mL). The combined organic extracts are washed with brine (10 mL), dried over Na2SO4 and evaporated under reduced pressure to afford the title compound as a brown oil (93 mg) which was used without further purification.

Workup

  1. temperatureThe mixture is cooled
  2. custompartitioned between NaHCO3 (5% aq., 5 mL) and EtOAc (15 mL)
  3. customThe layers are separated
  4. extractionthe aqueous phase extracted with further EtOAc (2×10 mL)
  5. washThe combined organic extracts are washed with brine (10 mL)
  6. dry with materialdried over Na2SO4
  7. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-36f50d0eeaee48988bd1e3248b64560c
Source dataset
uspto-grants-2012_05
Patent number
US08178530B2

Reaction notes

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