Potassium Carbonate → 2-Methoxy-N-(6-methylpyridin-3-yl)methyl-4-[5-(1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-ylamino]-benzamide

HRID 605994Notes

Reaction equation

HRID 605994 reaction equation
[NH:1]1[CH:5]=[C:4](B(O)O)[CH:3]=[N:2]1.Br[C:10]1[N:15]2[N:16]=[CH:17][N:18]=[C:14]2[C:13]([NH:19][C:20]2[CH:36]=[CH:35][C:23]([C:24]([NH:26][CH2:27][C:28]3[CH:29]=[N:30][C:31]([CH3:34])=[CH:32][CH:33]=3)=[O:25])=[C:22]([OH:37])[CH:21]=2)=[N:12][CH:11]=1.[C:38]([O-])([O-])=O.[K+].[K+].S(O)(C)(=O)=O.CO>CO.C(Cl)Cl>[CH3:38][O:37][C:22]1[CH:21]=[C:20]([NH:19][C:13]2[C:14]3[N:15]([N:16]=[CH:17][N:18]=3)[C:10]([C:4]3[CH:3]=[N:2][NH:1][CH:5]=3)=[CH:11][N:12]=2)[CH:36]=[CH:35][C:23]=1[C:24]([NH:26][CH2:27][C:28]1[CH:29]=[N:30][C:31]([CH3:34])=[CH:32][CH:33]=1)=[O:25]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 177502781H-Pyrazole-4-boronic acidHCID 866196654-(5-Bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-ylamino)-2-hydroxy-N-[(6-methyl-pyridin-3-yl)methyl]benzamideHCID 86749230Methanesulfonic acid methanol

Product 1

HCID 1359796172-Methoxy-N-(6-methylpyridin-3-yl)methyl-4-[5-(1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-ylamino]-benzamide

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Procedure

Pyrazole-4-boronic acid (19 mg, 0.17 mmol), 4-(5-bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-ylamino)-2-hydroxy-N-[(6-methyl-pyridin-3-yl)methyl]benzamide (40 mg, 0.085 mmol), K2CO3 (24 mg, 0.17 mmol) and Pd(dppf)Cl2CH2Cl2 (4 mg, 0.005 mmol) are weighed into a sealable tube. The tube is flushed with nitrogen and dioxane-water (4:1, 4 mL) is added. The tube is sealed, placed in an ultrasonic bath under a flow of nitrogen gas for 30 seconds and then placed into an oil bath at 85° C. The reaction is stirred for 28 hours, adding additional portions of boronic acid (10 mg) and catalyst (2 mg) after 2 h and 18 h. The crude mixture is absorbed onto SiO2 and purified by column chromatography, eluting with 1%-10% MeOH/DCM. The product obtained is redissolved in MeOH/DCM (4:1, 10 mL) and 0.1 M MsOH/MeOH (2 eq) is added, the solvents evaporated and the residue taken up in water and lyophillised to afford the title compound as its bis-mesylate salt (38 mg). LCMS: Rt 0.92 min (93.9%) m/z (ESI) 455 (M+H)+.

Workup

  1. customThe tube is flushed with nitrogen and dioxane-water (4:1, 4 mL)
  2. additionis added
  3. customThe tube is sealed
  4. customplaced into an oil bath at 85° C
  5. additionadding additional portions of boronic acid (10 mg) and catalyst (2 mg) after 2 h
  6. custom18 h
  7. customThe crude mixture is absorbed onto SiO2
  8. custompurified by column chromatography
  9. washeluting with 1%-10% MeOH/DCM
  10. customThe product obtained
  11. customthe solvents evaporated

Sources & evidence

ORD record
ord-70fc1ee019954c728bfd9a8e7971514c
Source dataset
uspto-grants-2011_03
Patent number
US07915256B2

Reaction notes

Loading…