Sodium Carbonate → HCID 117675704, compound

HRID 1526222Notes

Reaction equation

HRID 1526222 reaction equation
Br[C:2]1[C:3]([NH:31][C@@H:32]2[CH2:36][CH2:35][N:34]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:33]2)=[N:4][C:5]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([N:18]3[CH2:23][CH2:22][CH:21]([N:24]4[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]4)[CH2:20][CH2:19]3)=[CH:14][CH:13]=2)=[C:6]([C:8](=[O:10])[NH2:9])[N:7]=1.[N:44]1[CH:49]=[CH:48][C:47](B(O)O)=[CH:46][CH:45]=1.CN1CCCC1=O.C(=O)([O-])[O-].[Na+].[Na+]>O.C(OCC)(=O)C>[C:8]([C:6]1[N:7]=[C:2]([C:47]2[CH:48]=[CH:49][N:44]=[CH:45][CH:46]=2)[C:3]([NH:31][C@@H:32]2[CH2:36][CH2:35][N:34]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:33]2)=[N:4][C:5]=1[NH:11][C:12]1[CH:17]=[CH:16][C:15]([N:18]2[CH2:23][CH2:22][CH:21]([N:24]3[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]3)[CH2:20][CH2:19]2)=[CH:14][CH:13]=1)(=[O:10])[NH2:9]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 13387N-methyl-2-pyrrolidoneHCID 2734379(Pyridin-4-yl)boronic acidHCID 117675697HCID 117675697, compound

Product 1

HCID 117675704HCID 117675704, compoundYield 74.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

Under an argon atmosphere, to a mixture of tert-butyl (3R)-3-{[3-bromo-5-carbamoyl-6-({4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)pyrazin-2-yl]amino}pyrrolidine-1-carboxylate (300 mg), pyridin-4-ylboronic acid (196 mg), and N-methylpyrrolidone (6 mL) were added tetrakistriphenylphosphine palladium (0) (79 mg) and a 2 M aqueous sodium carbonate solution (797 μL), followed by stirring at 100° C. for 4 hours. After leaving to be cooled, ethyl acetate and water were added thereto, followed by stirring, and then the insoluble matter was separated by filtration. The organic phase was washed with saturated brine and dried over anhydrous magnesium sulfate, and then the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent; chloroform:methanol:28% aqueous ammonia=1:0:0-150:10:1) to obtain tert-butyl (3R)-3-{[5-carbamoyl-6-({4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)-3-(pyridin-4-yl)pyrazin-2-yl]amino}pyrrolidine-1-carboxylate (222 mg) as a yellow solid.

Workup

  1. customAfter leaving
  2. temperatureto be cooled
  3. stirringby stirring
  4. customthe insoluble matter was separated by filtration
  5. washThe organic phase was washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customthe solvent was evaporated under reduced pressure
  8. customThe obtained residue was purified by silica gel column chromatography (eluent; chloroform:methanol:28% aqueous ammonia=1:0:0-150:10:1)

Sources & evidence

ORD record
ord-d3eeb5de57484284a7ecdea32d88c18a
Source dataset
uspto-grants-2015_07
Patent number
US09085540B2

Reaction notes

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