1,2-Dimethoxyethane → 4-{4-[6-(3-Amino-phenyl)-imidazo[1,2-a]pyrazin-8-ylamino]-phenyl}-piperazine-1-carboxylic Acid Tert-Butyl Ester

HRID 751593Notes

Reaction equation

HRID 751593 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([NH:20][C:21]3[C:22]4[N:23]([CH:28]=[CH:29][N:30]=4)[CH:24]=[C:25](Br)[N:26]=3)=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].S(O)(O)(=O)=O.[NH2:36][C:37]1[CH:38]=[C:39](B(O)O)[CH:40]=[CH:41][CH:42]=1.NC1C=C(B(O)O)C=CC=1.C(=O)([O-])[O-].[Na+].[Na+].C(COC)OC>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([NH:20][C:21]3[C:22]4[N:23]([CH:28]=[CH:29][N:30]=4)[CH:24]=[C:25]([C:41]4[CH:40]=[CH:39][CH:38]=[C:37]([NH2:36])[CH:42]=4)[N:26]=3)=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 162111393-Aminophenylboronic Acid HemisulfateHCID 597547324-[4-(6-Bromo-imidazo[1,2-a]pyrazin-8-ylamino)-phenyl]-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 597546974-{4-[6-(3-Amino-phenyl)-imidazo[1,2-a]pyrazin-8-ylamino]-phenyl}-piperazine-1-carboxylic Acid Tert-Butyl Ester

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of 4-(6-bromoimidazo[1,2-a]pyrazin-8-ylamino)benzoic acid ethyl ester (13) (4,33 mmol), 3-aminophenylboronic acid hemisulfate (5,63 mmol), tetrakis(triphenylphosphine)palladium (0.2 mmol), 1N aqueous sodium carbonate solution (13 mL), and dimethoxyethane (70 mL) is heated at 95° C. for 2 days. The mixture is allowed to cool, treated with water (100 mL), and extracted with ethyl acetate (3×80 mL). The extracts are washed with water (2×75 mL) and brine (1×75 mL), dried over magnesium sulfate, and evaporated in vacuo. The residue is chromatographed over silica gel, eluting with ethyl acetate, to give 4-{4-[6-(3-amino-phenyl)-imidazo[1,2-a]pyrazin-8-ylamino]-phenyl}-piperazine-1-carboxylic acid tert-butyl ester (14) as a cream solid.

Workup

  1. temperatureto cool
  2. extractionextracted with ethyl acetate (3×80 mL)
  3. washThe extracts are washed with water (2×75 mL) and brine (1×75 mL)
  4. dry with materialdried over magnesium sulfate
  5. customevaporated in vacuo
  6. customThe residue is chromatographed over silica gel
  7. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-e4849771d0464c6c899f7f9b093153bf
Source dataset
uspto-grants-2008_07
Patent number
US07405295B2

Reaction notes

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