Cesium carbonate → 6-(5-(isoquinolin-1-ylamino)-2-methylphenyl)-2-(4-(4-methylpiperazin-1-yl)phenylamino)-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one

HRID 2092600

Reaction equation

HRID 2092600 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[NH2:47][C:48]1[CH:49]=[CH:50][C:51]([CH3:79])=[C:52]([N:54]2[CH2:77][CH2:76][C:57]3[N:58]=[C:59]([NH:62][C:63]4[CH:68]=[CH:67][C:66]([N:69]5[CH2:74][CH2:73][N:72]([CH3:75])[CH2:71][CH2:70]5)=[CH:65][CH:64]=4)[N:60]=[CH:61][C:56]=3[C:55]2=[O:78])[CH:53]=1.Br[C:81]1[C:90]2[C:85](=[CH:86][CH:87]=[CH:88][CH:89]=2)[CH:84]=[CH:83][N:82]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:81]1([NH:47][C:48]2[CH:49]=[CH:50][C:51]([CH3:79])=[C:52]([N:54]3[CH2:77][CH2:76][C:57]4[N:58]=[C:59]([NH:62][C:63]5[CH:68]=[CH:67][C:66]([N:69]6[CH2:70][CH2:71][N:72]([CH3:75])[CH2:73][CH2:74]6)=[CH:65][CH:64]=5)[N:60]=[CH:61][C:56]=4[C:55]3=[O:78])[CH:53]=2)[C:90]2[C:85](=[CH:86][CH:87]=[CH:88][CH:89]=2)[CH:84]=[CH:83][N:82]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 6409631-BromoisoquinolineHCID 673296826-(5-Amino-2-methyl-phenyl)-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-7,8-dihydro-6H-pyrido[4,3-d]pyrimidin-5-one

Product 1

HCID 673292006-(5-(isoquinolin-1-ylamino)-2-methylphenyl)-2-(4-(4-methylpiperazin-1-yl)phenylamino)-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Procedure

A mixture of 2,2′-Bis(diphenylphosphino)1,1′-binaphthyl [BINAP] (28.00 mg, 0.0451 mmol) and Palladium(II)acetate [Pd(OAc)2] (5.00 mg, 0.022 mmol) in dry toluene (3 ml) was stirred vigorously and nitrogen was bubbled through the suspension for 30 minutes. To this, 6-(5-amino-2-methylphenyl)-2-(4-(4-methylpiperazin-1-yl)phenylamino)-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one [45](200 mg, 0.451 mmol), 1-bromoisoquinoline (112.60 mg, 0.541 mmol) and dry cesium carbonate (443.0 mg, 1.352 mmol) was added. Nitrogen was bubbled through for another 30 minutes; the mixture was allowed to 15 reflux overnight. The mixture was cooled, diluted with ethyl acetate, water was added and the layers separated. The aqueous layer was extracted with ethyl acetate and the two organic extracts were combined. The organics were washed with brine, then dried (sodiumsulfate), filtered and concentrated. Further purification by silica gel chromatography using 5-10% ethyl acetate/hexane as eluent provided 6-(5-(isoquinolin-1-ylamino)-2-methylphenyl)-2-(4-(4-methylpiperazin-1-yl)phenylamino)-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one [60] as a yellow solid [Yield:—223 mg, 87.0%].

Workup

  1. customnitrogen was bubbled through the suspension for 30 minutes
  2. customNitrogen was bubbled through for another 30 minutes
  3. temperaturereflux overnight
  4. temperatureThe mixture was cooled
  5. additiondiluted with ethyl acetate, water
  6. additionwas added
  7. customthe layers separated
  8. extractionThe aqueous layer was extracted with ethyl acetate
  9. washThe organics were washed with brine
  10. dry with materialdried (sodiumsulfate)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customFurther purification by silica gel chromatography

Sources & evidence

ORD record
ord-ba7abcb8396e4eac92b6dc9e0cc9af77
Source dataset
uspto-grants-2013_05
Patent number
US08440679B2

Linked notes

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