Sodium Carbonate → HCID 117667132, compound

HRID 1526223Notes

Reaction equation

HRID 1526223 reaction equation
Br[C:2]1[N:7]=[C:6]([C:8]([NH2:10])=[O:9])[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)=[N:4][C:3]=1[NH:31][C@@H:32]1[CH2:36][CH2:35][NH:34][CH2:33]1.[C:37]1(B(O)O)[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.CN1CCCC1=O.C(=O)([O-])[O-].[Na+].[Na+]>O.C(Cl)(Cl)Cl>[CH3:30][N:27]1[CH2:28][CH2:29][N:24]([CH:21]2[CH2:22][CH2:23][N:18]([C:15]3[CH:16]=[CH:17][C:12]([NH:11][C:5]4[C:6]([C:8]([NH2:10])=[O:9])=[N:7][C:2]([C:37]5[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=5)=[C:3]([NH:31][C@@H:32]5[CH2:36][CH2:35][NH:34][CH2:33]5)[N:4]=4)=[CH:13][CH:14]=3)[CH2:19][CH2:20]2)[CH2:25][CH2:26]1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 13387N-methyl-2-pyrrolidoneHCID 66827Phenylboronic AcidHCID 117667463HCID 117667463, compound

Product 1

HCID 117667132HCID 117667132, compoundYield 95.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6212ChloroformSolvent

Conditions

Temperature
120 °C

Procedure

Under an argon atmosphere, to a mixture of 6-bromo-3-({4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)-5-[(3R)-pyrrolidin-3-ylamino]pyrazine-2-carboxamide (257 mg), phenylboronic acid (196 mg), and N-methylpyrrolidone (5.14 mL) were added tetrakistriphenylphosphine palladium (0) (80 mg) and a 2 M aqueous sodium carbonate solution (805 μL), followed by stirring at 120° C. for 4 hours. After leaving to be cooled, chloroform and water were added thereto, followed by stirring, and the insoluble matter was separated by filtration. The filtrate was subjected to liquid separation, and the organic phase was washed with saturated brine and dried over anhydrous magnesium sulfate. 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 3-({4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)-6-phenyl-5-[(3R)-pyrrolidin-3-ylamino]pyrazine-2-carboxamide (244 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. customThe filtrate was subjected to liquid separation
  6. washthe organic phase was washed with saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customThen, the solvent was evaporated under reduced pressure
  9. 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-14f75ec4d83d4c448e04dcc11d2b6b47
Source dataset
uspto-grants-2015_07
Patent number
US09085540B2

Reaction notes

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