Potassium Carbonate → Acetic acid 4-{8-[4-(4-isopropylpiperazin-1-yl)phenylamino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl}pyridin-2-ylmethyl ester

HRID 1783977Notes

Reaction equation

HRID 1783977 reaction equation
Br[C:2]1[N:7]2[N:8]=[CH:9][N:10]=[C:6]2[C:5]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([N:18]3[CH2:23][CH2:22][N:21]([CH:24]([CH3:26])[CH3:25])[CH2:20][CH2:19]3)=[CH:14][CH:13]=2)=[N:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].CC1(C)C(C)(C)OB([C:41]2[CH:46]=[CH:45][N:44]=[C:43]([CH2:47][O:48][C:49](=[O:51])[CH3:50])[CH:42]=2)O1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O1CCOCC1.O>[CH:24]([N:21]1[CH2:22][CH2:23][N:18]([C:15]2[CH:16]=[CH:17][C:12]([NH:11][C:5]3[C:6]4[N:7]([N:8]=[CH:9][N:10]=4)[C:2]([C:41]4[CH:46]=[CH:45][N:44]=[C:43]([CH2:47][O:48][C:49](=[O:51])[CH3:50])[CH:42]=4)=[CH:3][N:4]=3)=[CH:13][CH:14]=2)[CH2:19][CH2:20]1)([CH3:26])[CH3:25]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 49760405(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-YL)pyridin-2-YL)methyl acetateHCID 57590046(5-Bromo[1,2,4]triazolo[1,5-a]pyrazin-8-yl)-[4-(4-isopropylpiperazin-1-yl)-phenyl]amine

Product 1

HCID 57590057Acetic acid 4-{8-[4-(4-isopropylpiperazin-1-yl)phenylamino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl}pyridin-2-ylmethyl ester

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

A suspension of (5-bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)-[4-(4-isopropyl-piperazin-1-yl)phenyl]amine (300 mg, 0.723 mmol) and Pd(dppf)Cl2 (59 mg, 10 mol %) in 4/1 dioxane/water (5 mL) is stirred at rt and potassium carbonate (200 mg, 1.45 mmol, 2.0 equiv.) and acetic acid 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)pyridin-2-ylmethyl ester (300 mg, 1.08 mmol, 1.5 equiv.) are added. The resulting mixture is heated at 85° C. overnight. The resulting solution is partitioned between dichloromethane and water, and the organic layer is concentrated onto silica and purified by column chromatography (98/2 DCM/MeOH) to afford the title compound as a yellow solid. LCMS: Rt=0.78 min (100%), m/z 445 (M+H)+.

Workup

  1. temperatureThe resulting mixture is heated at 85° C. overnight
  2. customThe resulting solution is partitioned between dichloromethane and water
  3. concentrationthe organic layer is concentrated onto silica
  4. custompurified by column chromatography (98/2 DCM/MeOH)

Sources & evidence

ORD record
ord-fe5a3b077fb944c992dad3b05162cbbe
Source dataset
uspto-grants-2009_03
Patent number
US07501411B2

Reaction notes

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