Cesium carbonate → 2-({5-Chloro-2-[(1-ethyl-3-methyl-1H-pyrazol-5-yl)amino]-4-pyridinyl}amino)benzonitrile

HRID 1472569

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HRID 1472569 반응식
Cl[C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:16]=[CH:15][CH:14]=[CH:13][C:10]=2[C:11]#[N:12])[C:5]([Cl:17])=[CH:4][N:3]=1.[CH2:18]([N:20]1[C:24]([NH2:25])=[CH:23][C:22]([CH3:26])=[N:21]1)[CH3:19].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:17][C:5]1[C:6]([NH:8][C:9]2[CH:16]=[CH:15][CH:14]=[CH:13][C:10]=2[C:11]#[N:12])=[CH:7][C:2]([NH:25][C:24]2[N:20]([CH2:18][CH3:19])[N:21]=[C:22]([CH3:26])[CH:23]=2)=[N:3][CH:4]=1

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 27683831-Ethyl-3-methyl-1H-pyrazol-5-amineHCID 575168982-[(2,5-Dichloro-4-pyridinyl)amino]benzonitrile

생성물 1

HCID 593144512-({5-Chloro-2-[(1-ethyl-3-methyl-1H-pyrazol-5-yl)amino]-4-pyridinyl}amino)benzonitrile수율 45.6%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 312751,4-Dioxane용매

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온도
120 °C

실험 절차

To a 50 mL tube was added 2-[(2,5-dichloro-4-pyridinyl)amino]benzonitrile (738 mg, 2.80 mmol), 1-ethyl-3-methyl-1H-pyrazol-5-amine (350 mg, 2.80 mmol), BINAP (696 mg, 1.118 mmol), cesium carbonate (2733 mg, 8.39 mmol) and palladium(II) acetate (62.8 mg, 0.280 mmol) in 1,4-dioxane (15 mL). The reaction mixture was heated to 120° C. for 18 hr. Solid was filtered off and discarded and the solution was concentrated. Product was then dissolved in 1 M HCl (1 mL) and extracted with EtOAc. The organic layer was discarded. The water layer was neutralized with 1 M NaOH (to pH 8) and extracted with EtoAc. The organic layer was separated, washed with brine, dried over MgSO4, filtered and evaporated. The solid was the dissolved in 20 mL of EtOAc and 20 mL of water and 1 mL of acetic acid were added. The organic layer was separated, washed with brine, dried over MgSO4, filtered and evaporated. 2({5-Chloro-2-[(1-ethyl-3-methyl-1H-pyrazol-5-yl)amino]-4-pyridinyl}amino)benzonitrile (450 mg, 1.275 mmol, 45.6% yield) was isolated as orange foam. This product was used in the next step without further purification. LCMS (M+H)+=353.1; 1H NMR (400 MHz, DMSO-d6) ppm 1.19 (t, J=7.20 Hz, 3 H) 1.91 (s, 3 H) 3.84 (q, J=7.24 Hz, 2 H) 5.92 (s, 1 H) 6.03 (s, 1 H) 7.41 (td, J=7.64, 0.88 Hz, 1 H) 7.48 (d, J=8.08 Hz, 1 H) 7.76 (td, J=7.83, 1.52 Hz, 1 H) 7.91 (dd, J=7.83, 1.52 Hz, 1 H) 7.96 (s, 1 H) 8.47 (d, J=7.07 Hz, 1 H) 11.98 (br. s., 1 H)

후처리

  1. filtrationSolid was filtered off
  2. concentrationthe solution was concentrated
  3. dissolutionProduct was then dissolved in 1 M HCl (1 mL)
  4. extractionextracted with EtOAc
  5. extractionextracted with EtoAc
  6. customThe organic layer was separated
  7. washwashed with brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. customevaporated
  11. dissolutiondissolved in 20 mL of EtOAc
  12. addition20 mL of water and 1 mL of acetic acid were added
  13. customThe organic layer was separated
  14. washwashed with brine
  15. dry with materialdried over MgSO4
  16. filtrationfiltered
  17. customevaporated

출처 및 근거

ORD 기록
ord-a21a7e915ef3456ca99295ffcf858acc
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09012479B2

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