Water → Tert-butyl{1-[4-(2-phenyl-9-pyrazin-2-yl[1,2,4]triazolo[4',3':1,6]pyrido[2,3-b]pyrazin-3-yl)phenyl]cyclobutyl}carbamate

HRID 2104134Notes

Reaction equation

HRID 2104134 reaction equation
Cl[C:2]1[N:3]=[C:4]2[CH:17]=[CH:16][C:15]3=[N:18][N:19]=[C:20]([C:21]4[CH:26]=[N:25][CH:24]=[CH:23][N:22]=4)[N:14]3[C:5]2=[N:6][C:7]=1[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[C:27]([O:31][C:32](=[O:53])[NH:33][C:34]1([C:38]2[CH:43]=[CH:42][C:41](B3OC(C)(C)C(C)(C)O3)=[CH:40][CH:39]=2)[CH2:37][CH2:36][CH2:35]1)([CH3:30])([CH3:29])[CH3:28].C(=O)([O-])[O-].[K+].[K+].O>CN1C(=O)CCC1.CO.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C.O1CCOCC1.CN1C(=O)CCC1>[C:8]1([C:7]2[N:6]=[C:5]3[N:14]4[C:20]([C:21]5[CH:26]=[N:25][CH:24]=[CH:23][N:22]=5)=[N:19][N:18]=[C:15]4[CH:16]=[CH:17][C:4]3=[N:3][C:2]=2[C:41]2[CH:42]=[CH:43][C:38]([C:34]3([NH:33][C:32](=[O:53])[O:31][C:27]([CH3:30])([CH3:28])[CH3:29])[CH2:37][CH2:36][CH2:35]3)=[CH:39][CH:40]=2)[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

9

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 578054793-Chloro-2-phenyl-9-pyrazin-2-yl[1,2,4]triazolo[4',3':1,6]pyrido[2,3-b]pyrazineHCID 58326444tert-Butyl (1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclobutyl)carbamate

Product 1

HCID 57805478Tert-butyl{1-[4-(2-phenyl-9-pyrazin-2-yl[1,2,4]triazolo[4',3':1,6]pyrido[2,3-b]pyrazin-3-yl)phenyl]cyclobutyl}carbamate

Reagents, catalysts & solvents 4

HCID 178418851HCID 178418851, compoundCatalystHCID 13387N-methyl-2-pyrrolidoneSolventHCID 312751,4-DioxaneSolventHCID 22395687NMP MethanolSolvent

Conditions

Temperature
80 °C

Procedure

To a microwave vial was added 3-chloro-2-phenyl-9-pyrazin-2-yl[1,2,4]triazolo[4′,3′:1,6]pyrido[2,3-b]pyrazine (8-5, 0.151 g, 0.421 mmol), tert-butyl{1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]cyclobutyl}carbamate (8-6, 0.236 g, 0.631 mmol), potassium carbonate (0.174 g, 1.262 mmol), bis(tri-t-butylphosphine)palladium(0) (21.51 mg, 0.042 mmol), water (0.2 mL), NMP (0.2 mL), and 1.4 Dioxane (0.8 mL). The reaction mixture was then heated to 80° C. under microwave irradiation for 10 minutes. The reaction mixture was then permitted to cool to room temperature, diluted with NMP/MeOH, and filtered through a syringe filter. The resulting residue was then purified by reverse phase column chromatography (Sunfire C18) eluting with 5 to 100% acetonitrile/(0.1% TFA/water) gradient. The appropriate fractions were then concentrated in vacuo to give 8-7 as a green solid. HRMS (M+H)+: observed=571.2591, calculated=571.2565.

Workup

  1. temperatureto cool to room temperature
  2. filtrationfiltered through a syringe
  3. filtrationfilter
  4. customThe resulting residue was then purified by reverse phase column chromatography (Sunfire C18)
  5. washeluting with 5 to 100% acetonitrile/(0.1% TFA/water) gradient
  6. concentrationThe appropriate fractions were then concentrated in vacuo

Sources & evidence

ORD record
ord-93c64bc59fb84959a0ee8feea4b01f26
Source dataset
uspto-grants-2009_08
Patent number
US07576209B2

Reaction notes

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