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 79158노트

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HRID 79158 반응식
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

참가 물질

6

반응물 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

생성물 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)acetonitrile수율 54.6%

시약·촉매·용매 1

HCID 9811564Bis(dibenzylideneacetone)palladium촉매

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온도
105 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-180c6528b64449868d97d93dd7bc3a97
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08841312B2

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