Hydrochloric Acid → 3-{8-[4-(Morpholine-4-carbonyl)-phenylamino]-imidazo[1,2-a]pyrazin-6-yl}-benzoic acid

HRID 751588Notes

Reaction equation

HRID 751588 reaction equation
Br[C:2]1[N:3]=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)=[O:19])=[CH:14][CH:13]=2)[C:5]2[N:6]([CH:8]=[CH:9][N:10]=2)[CH:7]=1.[C:26]([C:29]1[CH:30]=[C:31](B(O)O)[CH:32]=[CH:33][CH:34]=1)([OH:28])=[O:27].C([O-])([O-])=O.[Na+].[Na+].Cl>COCCOC.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>[N:20]1([C:18]([C:15]2[CH:16]=[CH:17][C:12]([NH:11][C:4]3[C:5]4[N:6]([CH:8]=[CH:9][N:10]=4)[CH:7]=[C:2]([C:33]4[CH:34]=[C:29]([CH:30]=[CH:31][CH:32]=4)[C:26]([OH:28])=[O:27])[N:3]=3)=[CH:13][CH:14]=2)=[O:19])[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 27339573-Carboxyphenylboronic acidHCID 59754722[4-(6-Bromo-imidazo[1,2-a]pyrazin-8-ylamino)-phenyl]-morpholin-4-yl-methanone

Product 1

HCID 597546943-{8-[4-(Morpholine-4-carbonyl)-phenylamino]-imidazo[1,2-a]pyrazin-6-yl}-benzoic acid

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
95 °C

Procedure

The bromide (8) (2,46 mmol) is dissolved in 10 mL DME (ethylene glycol, dimethyl ether) in a sealable pressure vessel and N2 is bubbled through for 10 min. Tetrakis(triphenylphosphine)palladium (0.24 mmol) is added and N2 is bubbled through the reaction for another 10 minutes. 3-Carboxyphenyl boronic acid (3.1 mmol) and 1N Na2CO3 solution (10 mL) are then added, the vessel sealed, and the reaction heated to 95° C. for 16 hrs. with vigorous stirring. After cooling to room temperature, the reaction is acidified to pH 3 with 1N HCl and extracted with ethyl acetate (3×25 mL). The pooled ethyl acetate layers are washed with brine, dried over sodium sulfate, and the solvent removed in vacuo. The resulting solid is then dissolved in a minimal volume of CH2Cl2 and precipitated out as a whitish-tan solid by slow addition of ethyl acetate (5 mL) followed by hexanes (30 mL) to yield 3-{8-[4-(Morpholine-4-carbonyl)-phenylamino]-imidazo[1,2-a]pyrazin-6-yl}-benzoic acid (9).

Workup

  1. customN2 is bubbled through for 10 min
  2. customN2 is bubbled through the reaction for another 10 minutes
  3. customthe vessel sealed
  4. temperatureAfter cooling to room temperature
  5. extractionextracted with ethyl acetate (3×25 mL)
  6. washThe pooled ethyl acetate layers are washed with brine
  7. dry with materialdried over sodium sulfate
  8. customthe solvent removed in vacuo
  9. dissolutionThe resulting solid is then dissolved in a minimal volume of CH2Cl2
  10. customprecipitated out as a whitish-tan solid by slow addition of ethyl acetate (5 mL)

Sources & evidence

ORD record
ord-c498ec2c4a4b4c5d8b7ca5d8da766917
Source dataset
uspto-grants-2008_07
Patent number
US07405295B2

Reaction notes

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