Nitrogen → N-(2-(2-fluoro-5-methylphenyl)pyridin-4-yl)-2-(piperidin-4-yl)-2H-pyrazolo[4,3-b]pyridin-7-amine

HRID 1522613Notes

Reaction equation

HRID 1522613 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[C:9]1[CH:14]=[C:13]([NH2:15])[CH:12]=[CH:11][N:10]=1.I[C:17]1[C:18]2[C:19](=[CH:23][N:24]([CH:26]3[CH2:31][CH2:30][N:29](C(OC(C)(C)C)=O)[CH2:28][CH2:27]3)[N:25]=2)[N:20]=[CH:21][CH:22]=1.CC(C)([O-])C.N#N.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>C1(C)C(C)=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[C:9]1[CH:14]=[C:13]([NH:15][C:17]2[C:18]3[C:19](=[CH:23][N:24]([CH:26]4[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]4)[N:25]=3)[N:20]=[CH:21][CH:22]=2)[CH:12]=[CH:11][N:10]=1

Participants

8

Reactant 5

HCID 947NitrogenHCID 45749132-Methylpropan-2-olateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 674695782-(2-Fluoro-5-methylphenyl)pyridin-4-amineHCID 67469655tert-butyl 4-(7-iodo-2H-pyrazolo[4,3-b]pyridin-2-yl)piperidine-1-carboxylate

Product 1

HCID 54670504N-(2-(2-fluoro-5-methylphenyl)pyridin-4-yl)-2-(piperidin-4-yl)-2H-pyrazolo[4,3-b]pyridin-7-amineYield 87%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 7237O-XyleneSolvent

Conditions

Temperature
120 °C

Procedure

A solution of 2-(2-fluoro-5-methylphenyl)pyridin-4-amine (42.5 mg, 0.210 mmol), tert-butyl 4-(7-iodo-2H-pyrazolo[4,3-b]pyridin-2-yl)piperidine-1-carboxylate (60 mg, 0.140 mmol) and t-butoxide (18.85 mg, 0.196 mmol) in xylene (3 mL) was sparged with N2 and then 2-dicyclohexylphosphino-2′,4′,6′-tri-iso-propyl-1,1′-biphenyl (13.36 mg, 0.028 mmol) and tris(dibenzylideneacetone)dipalladium(0) (12.83 mg, 0.014 mmol) were added and the mixture was heated at 120° C. overnight. The reaction was cooled, concentrated, the residue treated with dichloromethane/TFA (1/1) and the solvent was removed in vacuo. The residue was dissolved with methanol and purified with preparative HPLC using a Sunfire Prep 5 μm C18, 75×30 mm column eluting with a gradient of 15-40% acetonitrile (containing 0.035% TFA) in water (containing 0.05% TFA) to give N-(2-(2-fluoro-5-methylphenyl)pyridin-4-yl)-2-(piperidin-4-yl)-2H-pyrazolo[4,3-b]pyridin-7-amine (49 mg, 87%)

Workup

  1. temperatureThe reaction was cooled
  2. concentrationconcentrated
  3. additionthe residue treated with dichloromethane/TFA (1/1)
  4. customthe solvent was removed in vacuo
  5. dissolutionThe residue was dissolved with methanol
  6. custompurified with preparative HPLC
  7. washeluting with a gradient of 15-40% acetonitrile (containing 0.035% TFA) in water (containing 0.05% TFA)

Sources & evidence

ORD record
ord-053819068b43460388768d6809178fab
Source dataset
uspto-grants-2015_07
Patent number
US09073918B2

Reaction notes

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