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Toluene → 2'-Cyano-4'-methyl-N-((2-methylpyrimidin-5-yl)methyl)-5-(pyrrolidine-1-carbonyl)biphenyl-3-carboxamide

HRID 1845188
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HRID 1845188 반응식
Br[C:2]1[CH:3]=[C:4]([CH:16]=[C:17]([C:19]([N:21]2[CH2:25][CH2:24][CH2:23][CH2:22]2)=[O:20])[CH:18]=1)[C:5]([NH:7][CH2:8][C:9]1[CH:10]=[N:11][C:12]([CH3:15])=[N:13][CH:14]=1)=[O:6].[CH3:26][C:27]1[CH:28]=[CH:29][C:30](B2OC(C)(C)C(C)(C)O2)=[C:31]([CH:34]=1)[C:32]#[N:33].C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.C(O)C>[C:32]([C:31]1[CH:34]=[C:27]([CH3:26])[CH:28]=[CH:29][C:30]=1[C:2]1[CH:18]=[C:17]([C:19]([N:21]2[CH2:25][CH2:24][CH2:23][CH2:22]2)=[O:20])[CH:16]=[C:4]([C:5]([NH:7][CH2:8][C:9]2[CH:10]=[N:11][C:12]([CH3:15])=[N:13][CH:14]=2)=[O:6])[CH:3]=1)#[N:33]
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참가 물질

8

반응물 4

HCID 1140TolueneHCID 10796Cesium carbonateHCID 581880073-Bromo-N-((2-methylpyrimidin-5-yl)methyl)-5-(pyrrolidine-1-carbonyl)benzamideHCID 584073295-Methyl-2-(tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile

생성물 1

HCID 442230412'-Cyano-4'-methyl-N-((2-methylpyrimidin-5-yl)methyl)-5-(pyrrolidine-1-carbonyl)biphenyl-3-carboxamide

시약·촉매·용매

3
HCID 178418397HCID 178418397, 화합물촉매HCID 702Ethanol용매HCID 962Water용매

반응 조건

온도
90 °C

실험 절차

Into a Parr pressure reactor were charged 3-bromo-N-((2-methylpyrimidin-5-yl)methyl)-5-(pyrrolidine-1-carbonyl)benzamide (240 mg, 0.48 mmol), 5-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (160 mg, 0.58 mmol) (WO 2008/130481), toluene (5 mL), ethanol (1 mL), cesium carbonate (170 mg, 0.52 mmol), and water (0.5 mL). The mixture was degassed and purged with nitrogen several times and then tetrakis(triphenylphosphine)palladium(0) (28 mg, 0.024 mmol) was added. The tube was sealed and the mixture was heated at 90° C. overnight. After cooling, the mixture was filtered through Celite and the filtrate was concentrated. The residue was purified via flash chromatography and then preparative HPLC to afford the desired product as a white solid.

후처리

  1. customThe mixture was degassed
  2. custompurged with nitrogen several times
  3. customThe tube was sealed
  4. temperatureAfter cooling
  5. filtrationthe mixture was filtered through Celite
  6. concentrationthe filtrate was concentrated
  7. customThe residue was purified via flash chromatography

출처 및 근거

ORD 기록
ord-c778e4b7bccd4dbdb97bea296dc4abc4
출처 데이터셋
uspto-grants-2015_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08946439B2

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