Cesium carbonate → 3-(4-Chloro-2-morpholinothiazol-5-yl)-2,6-dimethyl-8-(pentan-3-yl)imidazo[1,2-b]pyridazine

HRID 1432684노트

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HRID 1432684 반응식
[CH2:1]([CH:3]([C:6]1[C:7]2[N:8]([C:13](I)=[C:14]([CH3:16])[N:15]=2)[N:9]=[C:10]([CH3:12])[CH:11]=1)[CH2:4][CH3:5])[CH3:2].[O:18]1[CH2:23][CH2:22][N:21]([C:24]2[S:25][CH:26]=[C:27]([Cl:29])[N:28]=2)[CH2:20][CH2:19]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CC([O-])=O.CC([O-])=O.[Pd+2].[Cu](I)I.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:29][C:27]1[N:28]=[C:24]([N:21]2[CH2:20][CH2:19][O:18][CH2:23][CH2:22]2)[S:25][C:26]=1[C:13]1[N:8]2[N:9]=[C:10]([CH3:12])[CH:11]=[C:6]([CH:3]([CH2:4][CH3:5])[CH2:1][CH3:2])[C:7]2=[N:15][C:14]=1[CH3:16]

참가 물질

7

반응물 3

HCID 10796Cesium carbonateHCID 534400954-(4-Chlorothiazol-2-YL)morpholineHCID 577526818-(1-Ethyl-propyl)-3-iodo-2,6-dimethyl-imidazo[1,2-b]pyridazine

생성물 1

HCID 115462553-(4-Chloro-2-morpholinothiazol-5-yl)-2,6-dimethyl-8-(pentan-3-yl)imidazo[1,2-b]pyridazine수율 106.5%

시약·촉매·용매 3

HCID 11776Triphenylphosphine촉매2회HCID 83717Copper iodide촉매HCID 167845palladium(II) acetate촉매2회

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온도
120 °C

실험 절차

A 20 L reactor flask under nitrogen is charged with 2900 ml of dry and degassed DMF then with 8-(1-ethyl-propyl)-3-iodo-2,6-dimethyl-imidazo[1,2-b]pyridazine (287 g, 0.836 mol), 2-morpholino-4-chlorothiazole (205.4 g, 1.01 mol, 1.2 equv.), Pd(OAc)2 (3.74 g, 7.91 mmol, 0.01 equiv.), triphenylphosphine (8.77 g, 33.1 mmol, 0.04 equiv.), Copper iodide (8 g, 41.59 mmol, 0.05 equiv.) and cesium carbonate (544.9 g, 1.65 mol). The reaction mixture is heated at 120° C. After 16 h at 120° C., 1.87 g of Pd(OAc)2 and 4.38 g of triphenylphosphine more is added. After 1 h, the mixture is cooled, quenched with NH4Cl solution (4300 mL) and extracted with MTBE (2900 mL), the aqueous phase is extracted twice more with 2000 ml of MTBE. The organic phases are washed with sat NaCl aq (2000 mL), then treated with charcoal 72 g in flask bottle and filtered on Celite®. The filtrate is concentrated under vacuum to afford 373.8 g (79.3%) of the title compound which is 81.4%-area HPLC analysis the rest being solvent and with no detectable Example 200 by-product.

후처리

  1. additionA 20 L reactor flask under nitrogen is charged with 2900 ml
  2. customof dry
  3. customdegassed DMF
  4. waitAfter 1 h
  5. temperaturethe mixture is cooled
  6. customquenched with NH4Cl solution (4300 mL)
  7. extractionextracted with MTBE (2900 mL)
  8. extractionthe aqueous phase is extracted twice more with 2000 ml of MTBE
  9. washThe organic phases are washed with sat NaCl aq (2000 mL)
  10. additiontreated with charcoal 72 g in flask bottle
  11. filtrationfiltered on Celite®
  12. concentrationThe filtrate is concentrated under vacuum

출처 및 근거

ORD 기록
ord-c31b5e8e73394118a08cdf374d1bb9b6
출처 데이터셋
uspto-grants-2009_11
특허 번호
US07612067B2

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