Cesium carbonate → (1-(6-((9-Cyclopentyl-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-pyridinyl)-4-piperidinyl)acetonitrile

HRID 79158ノート

反応式

HRID 79158 の反応式
CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+].Cl[C:50]1[N:55]=[CH:54][C:53]([N:56]2[CH2:61][CH2:60][CH:59]([CH2:62][C:63]#[N:64])[CH2:58][CH2:57]2)=[CH:52][CH:51]=1.[CH:65]1([N:70]2[C:74]3[N:75]=[C:76]([NH2:79])[N:77]=[CH:78][C:73]=3[C:72]3[CH:80]=[CH:81][N:82]=[C:83]([F:84])[C:71]2=3)[CH2:69][CH2:68][CH2:67][CH2:66]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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:65]1([N:70]2[C:74]3[N:75]=[C:76]([NH:79][C:50]4[N:55]=[CH:54][C:53]([N:56]5[CH2:61][CH2:60][CH:59]([CH2:62][C:63]#[N:64])[CH2:58][CH2:57]5)=[CH:52][CH:51]=4)[N:77]=[CH:78][C:73]=3[C:72]3[CH:80]=[CH:81][N:82]=[C:83]([F:84])[C:71]2=3)[CH2:66][CH2:67][CH2:68][CH2:69]1

参加物

6

反応物 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 582996889-Cyclopentyl-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amineHCID 86654439(1-(6-Chloro-3-pyridinyl)-4-piperidinyl)acetonitrile

生成物 1

HCID 67234663(1-(6-((9-Cyclopentyl-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-pyridinyl)-4-piperidinyl)acetonitrile収率 54.6%

試薬・触媒・溶媒 1

HCID 9811564Bis(dibenzylideneacetone)palladium触媒

反応条件

温度
105 °C

実験手順

To tris(dibenzylideneacetone)dipalladium (0) (0.0147 g, 0.0160 mmol), xantphos (0.0186 g, 0.0321 mmol), Cs2CO3 (0.0975 g, 0.299 mmol), 2-(1-(6-chloropyridin-3-yl)piperidin-4-yl)acetonitrile (0.0504 g, 0.214 mmol), and compound 245 (0.0580 g, 0.214 mmol) was added degassed (Ar) dioxane (1.0 mL). The reaction was stirred at 105° C. overnight. After 16 h, the reaction was cooled to room temperature and loaded directly onto silica gel. Crystallization from THF and HCl salt formation provided compound 252 (55 mg). 1H NMR (400 MHz, DMSO-d6) δ 1.43 (d, J=10.56 Hz, 2 H) 1.66-1.81 (m, 2 H) 1.86 (d, J=11.35 Hz, 3 H) 2.05 (d, J=6.26 Hz, 2 H) 2.15 (br. s., 2 H) 2.19-2.31 (m, 2 H) 2.59 (d, J=5.87 Hz, 2 H) 2.85 (t, J=11.74 Hz, 2 H) 3.75 (d, J=12.13 Hz, 2 H) 5.53 (quin, J=9.10 Hz, 1 H) 7.68 (d, J=9.39 Hz, 1 H) 8.00 (br. s., 1 H) 8.15 (d, J=5.09 Hz, 1 H) 8.20 (dd, J=9.39, 2.74 Hz, 1 H) 8.30 (dd, J=4.89, 2.93 Hz, 1 H) 9.55 (s, 1 H) 11.80 (br. s., 1 H) ppm.

後処理

  1. customdegassed (Ar) dioxane (1.0 mL)
  2. waitAfter 16 h
  3. temperaturethe reaction was cooled to room temperature
  4. customCrystallization from THF and HCl salt formation

出典と根拠

ORDレコード
ord-180c6528b64449868d97d93dd7bc3a97
出典データセット
uspto-grants-2014_09
特許番号
US08841312B2

反応ノート

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