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Lithium Chloride → 6'-(Pyridazin-4-yl)-2-fluoro-5-(4-piperidin-1-ylmethylphenyl)-[3,4']bipyridinyl-3'-ylamine

HRID 1888613
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HRID 1888613 반응식
Br[C:2]1[N:7]=[CH:6][C:5]([NH2:8])=[C:4]([C:9]2[C:10]([F:28])=[N:11][CH:12]=[C:13]([C:15]3[CH:20]=[CH:19][C:18]([CH2:21][N:22]4[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]4)=[CH:17][CH:16]=3)[CH:14]=2)[CH:3]=1.C([Sn](CCCC)(CCCC)[C:34]1[CH:39]=[CH:38][N:37]=[N:36][CH:35]=1)CCC.[Cl-].[Li+]>O1CCOCC1.C(Cl)Cl.CO.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[N:36]1[CH:35]=[CH:34][C:39]([C:2]2[N:7]=[CH:6][C:5]([NH2:8])=[C:4]([C:9]3[C:10]([F:28])=[N:11][CH:12]=[C:13]([C:15]4[CH:20]=[CH:19][C:18]([CH2:21][N:22]5[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]5)=[CH:17][CH:16]=4)[CH:14]=3)[CH:3]=2)=[CH:38][N:37]=1
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참가 물질

8

반응물 3

HCID 433294Lithium ChlorideHCID 64097334-(Tributylstannyl)pyridazineHCID 582666266'-Bromo-2-fluoro-5-(4-piperidin-1-ylmethylphenyl)-[3,4]bipyridinyl-3'-ylamine

생성물 1

HCID 582666076'-(Pyridazin-4-yl)-2-fluoro-5-(4-piperidin-1-ylmethylphenyl)-[3,4']bipyridinyl-3'-ylamine

시약·촉매·용매 4

HCID 11979704
Tetrakis(triphenylphosphine)palladium
촉매
HCID 887Methanol용매
HCID 6344Dichloromethane용매
HCID 312751,4-Dioxane용매

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온도
110 °C

실험 절차

A mixture of 6′-bromo-2-fluoro-5-(4-piperidin-1-ylmethylphenyl)-[3,4′]bipyridinyl-3′-ylamine (200 mg, 0.45 mmol), 4-(tributylstannyl)pyridazine (334 mg, 0.91 mmol) and lithium chloride (192 mg, 4.5 mmol) in 1,4-dioxane (5 mL) was degassed and flushed with nitrogen. Tetrakis(triphenylphosphine)-palladium(0) (39 mg, 0.034 mmol) was added and the reaction was heated at 110° C. for 24 h. The cooled reaction mixture was diluted with DCM (20 mL) and methanol (2 mL) and washed with water (15 mL). The organic phase was separated, dried over sodium sulfate, filtered and evaporated in vacuo to afford a residue that was purified by flash chromotagraphy (silica, 10 g column, Biotage, 0-10% methanol in DCM containing 0 1% ammonia) to afford a brown residue that was taken to the next step without further purification.

후처리

  1. customwas degassed
  2. customflushed with nitrogen
  3. customThe cooled reaction mixture
  4. washwashed with water (15 mL)
  5. customThe organic phase was separated
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customto afford a residue that
  10. customwas purified by flash chromotagraphy (silica, 10 g column, Biotage, 0-10% methanol in DCM containing 0 1% ammonia)
  11. customto afford a brown residue that
  12. customwas taken to the next step without further purification

출처 및 근거

ORD 기록
ord-623d1791ec53467c8dc6a3ad728b9dc1
출처 데이터셋
uspto-grants-2013_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08501765B2

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