Potassium Phosphate, Tribasic → HCID 117666962, compound

HRID 1526227Notes

Reaction equation

HRID 1526227 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:8][C:9]2[N:10]=[C:11]([NH:20][C:21]3[CH:26]=[CH:25][C:24]([N:27]4[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]4)=[CH:23][CH:22]=3)[C:12]([C:17]([NH2:19])=[O:18])=[N:13][C:14]=2[CH2:15][CH3:16])[CH:5]=[N:6][CH:7]=1.[C:34](=[NH:47])([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O.CN1CCCC1=O.COCCOC>[C:35]1([C:34](=[N:47][C:2]2[CH:3]=[C:4]([O:8][C:9]3[N:10]=[C:11]([NH:20][C:21]4[CH:26]=[CH:25][C:24]([N:27]5[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]5)=[CH:23][CH:22]=4)[C:12]([C:17]([NH2:19])=[O:18])=[N:13][C:14]=3[CH2:15][CH3:16])[CH:5]=[N:6][CH:7]=2)[C:41]2[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=2)[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 136809Benzophenone imineHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphane2×HCID 117667156HCID 117667156, compound

Product 1

HCID 117666962HCID 117666962, compound

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 5-[(5-bromopyridin-3-yl)oxy]-6-ethyl-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazine-2-carboxamide (370 mg), benzophenoneimine (145 μL), a tris(dibenzylideneacetone)dipalladium (0) chloroform complex (22 mg), di-tert-butyl (2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (28 mg), potassium phosphate (383 mg), and 1,2-dimethoxyethane (3 mL) was stirred at 80° C. for 10 hours under a nitrogen atmosphere. To the reactant was added N-methylpyrrolidone (3 mL), and a tris(dibenzylideneacetone)dipalladium (0) chloroform complex (22 mg) and di-tert-butyl (2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (28 mg) were added thereto, followed by stirring at 80° C. for 10 hours. Water was added thereto, followed by extraction with ethyl acetate. 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=1:0-9:1) to obtain 5-({5-[(diphenylmethylene)amino]pyridin-3-yl}oxy)-6-ethyl-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazine-2-carboxamide (133 mg) as a brown amorphous substance.

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe organic phase was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography (eluent; chloroform:methanol=1:0-9:1)

Sources & evidence

ORD record
ord-d4b5bd599c77447cbff23304ba123384
Source dataset
uspto-grants-2015_07
Patent number
US09085540B2

Reaction notes

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