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 1853966

反応式

HRID 1853966 の反応式
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

参加物

7

反応物 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

生成物 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

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 1140Toluene溶媒

実験手順

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%].

後処理

  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

出典と根拠

ORDレコード
ord-85ce5472d118474aa16d7b9afba86e4b
出典データセット
uspto-grants-2015_02
特許番号
US08962637B2

関連ノート

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