Water → 4-{[3-(4-Hydroxy-phenyl)-6-methyl-imidazo[1,2-a]pyrazin-8-ylamino]-methyl}-benzenesulfonamide

HRID 1809197

Reaction equation

HRID 1809197 reaction equation
Br[C:2]1[N:6]2[CH:7]=[C:8]([CH3:23])[N:9]=[C:10]([NH:11][CH2:12][C:13]3[CH:18]=[CH:17][C:16]([S:19]([NH2:22])(=[O:21])=[O:20])=[CH:15][CH:14]=3)[C:5]2=[N:4][CH:3]=1.CC1(C)C(C)(C)OB([C:32]2[CH:37]=[CH:36][C:35]([OH:38])=[CH:34][CH:33]=2)O1.C([O-])([O-])=O.[K+].[K+].O.O(C1C=CC=CC=1P(C1C=CC=CC=1)C1C=CC=CC=1)C1C=CC=CC=1P(C1C=CC=CC=1)C1C=CC=CC=1>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[OH:38][C:35]1[CH:36]=[CH:37][C:32]([C:2]2[N:6]3[CH:7]=[C:8]([CH3:23])[N:9]=[C:10]([NH:11][CH2:12][C:13]4[CH:18]=[CH:17][C:16]([S:19]([NH2:22])(=[O:21])=[O:20])=[CH:15][CH:14]=4)[C:5]3=[N:4][CH:3]=2)=[CH:33][CH:34]=1

Participants

8

Reactant 5

HCID 962WaterHCID 11430Potassium CarbonateHCID 27346244-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenolHCID 4285986Bis[2-(diphenylphosphino)phenyl] etherHCID 583371644-[(3-Bromo-6-methyl-imidazo[1,2-a]pyrazin-8-ylamino)-methyl]-benzenesulfonamide

Product 1

HCID 1359983054-{[3-(4-Hydroxy-phenyl)-6-methyl-imidazo[1,2-a]pyrazin-8-ylamino]-methyl}-benzenesulfonamideYield 29.3%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
88 °C

Procedure

A mixture of 4-[(3-bromo-6-methyl-imidazo[1,2-a]pyrazin-8-ylamino)-methyl]-benzenesulfonamide (0.1 g, 0.252 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenol (0.061 g, 0.277 mmol), K2CO3 1.5M in water (0.34 mL, 0.504 mmol), Pd(OAc)2 (3.0 mg, 0.013 mmol), and (oxidi-2,1-phenylene)bis(diphenylphosphine) (14 mg, 0.026 mmol) in DMF 1 mL was stirred at 88° C. overnight. Then the reaction mixture is filtered through cotton, diluted with AcOEt, washed with water, the organic layer dried with MgSO4 (anhydrous), filtered and evaporated. The crude mixture is purified by prep. HPLC under acid conditions using a gradient of 0.1% formic acid in H2O/0.1% formic acid in acetonitrile (95/5:5 min, 9/1:13 min, 0/1:4 min) to give 4-{[3-(4-hydroxy-phenyl)-6-methyl-imidazo[1,2-a]pyrazin-8-ylamino]-methyl}-benzenesulfonamide as a brown oil (30.2 mg) LC-MS m/z 410 [M+H]+.

Workup

  1. filtrationThen the reaction mixture is filtered through cotton
  2. additiondiluted with AcOEt
  3. washwashed with water
  4. dry with materialthe organic layer dried with MgSO4 (anhydrous)
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude mixture is purified by prep
  8. customa gradient of 0.1% formic acid in H2O/0.1% formic acid in acetonitrile (95/5:5 min, 9/1:13 min, 0/1:4 min)

Sources & evidence

ORD record
ord-a5d0a2a6009d443daba0c4e424880dc4
Source dataset
uspto-grants-2013_01
Patent number
US08362018B2

Linked notes

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