Sodium Carbonate → HCID 131734227, compound

HRID 1498050Notes

Reaction equation

HRID 1498050 reaction equation
[N:1]1([C:5]2[C:10]3=[C:11]([C:14]4[CH:15]=[N:16][N:17]([CH3:20])[C:18]=4Br)[N:12]=[CH:13][N:9]3[N:8]=[CH:7][N:6]=2)[CH2:4][CH2:3][CH2:2]1.[F:21][C:22]([F:33])([F:32])[C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1.[C:34](=[O:37])([O-])[O-:35].[Na+].[Na+]>C(O)C.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:21][C:22]([F:33])([F:32])[C:34]([OH:35])=[O:37].[N:1]1([C:5]2[C:10]3=[C:11]([C:14]4[CH:15]=[N:16][N:17]([CH3:20])[C:18]=4[C:26]4[CH:27]=[CH:28][C:23]([C:22]([F:33])([F:32])[F:21])=[CH:24][CH:25]=4)[N:12]=[CH:13][N:9]3[N:8]=[CH:7][N:6]=2)[CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 68181924HCID 68181924, compound

Product 1

HCID 131734227HCID 131734227, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Procedure

4-(Azetidin-1-yl)-5-(5-bromo-1-methyl-1H-pyrazol-4-yl)imidazo[5,1-f][1,2,4]triazine (15 mg, 0.045 mmol), [4-(trifluoromethyl)phenyl]boronic acid (9.50 mg, 0.0500 mmol), tetrakis(triphenylphosphine)palladium(0) (4.6 mg, 0.0040 mmol) and sodium carbonate (9.5 mg, 0.090 mmol) were combined in ethanol (4 mL), and the reaction mixture was heated at reflux for 18 hours. After filtration, the filtrate was concentrated in vacuo and purified via reversed-phase HPLC (Column: Waters Sunfire C18, 19×100 mm, 5 μm; Mobile phase A: 0.05% TFA in water (v/v); Mobile phase B: 0.05% TFA in acetonitrile (v/v); Gradient: 5% to 100% B). Yield: 4.5 mg, 0.011 mmol, 24%. Retention time: 2.32 minutes (Column: Waters Atlantis dC18, 4.6×50 mm, 5 μm; Mobile phase A: 0.05% TFA in water (v/v); Mobile phase B: 0.05% TFA in acetonitrile (v/v); Gradient: linear, 5% to 95% B over 4.0 minutes; Flow rate: 2 mL/minute). LCMS m/z 400.2 (M+1).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux for 18 hours
  3. filtrationAfter filtration
  4. concentrationthe filtrate was concentrated in vacuo
  5. custompurified via reversed-phase HPLC (Column: Waters Sunfire C18, 19×100 mm, 5 μm; Mobile phase A: 0.05% TFA in water (v/v); Mobile phase B: 0.05% TFA in acetonitrile (v/v); Gradient: 5% to 100% B)
  6. customRetention time: 2.32 minutes (Column: Waters Atlantis dC18, 4.6×50 mm, 5 μm; Mobile phase A: 0.05% TFA in water (v/v); Mobile phase B: 0.05% TFA in acetonitrile (v/v); Gradient: linear, 5% to 95% B over 4.0 minutes; Flow rate: 2 mL/minute)

Sources & evidence

ORD record
ord-909aa944897841299ab6384adf0510f7
Source dataset
uspto-grants-2015_12
Patent number
US09200000B2

Reaction notes

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