Cesium carbonate → 6-Chloro-4-(5-cyclobutylaminomethyl-pyrazin-2-ylamino)-2-methyl-2H-pyridazin-3-one

HRID 449638노트

반응식

HRID 449638 반응식
[CH:1]1([NH:5][CH2:6][C:7]2[N:8]=[CH:9][C:10]([NH2:13])=[N:11][CH:12]=2)[CH2:4][CH2:3][CH2:2]1.Br[C:15]1[C:16](=[O:23])[N:17]([CH3:22])[N:18]=[C:19]([Cl:21])[CH:20]=1.C([O-])([O-])=O.[Cs+].[Cs+].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>O1CCOCC1.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]>[Cl:21][C:19]1[CH:20]=[C:15]([NH:13][C:10]2[CH:9]=[N:8][C:7]([CH2:6][NH:5][CH:1]3[CH2:2][CH2:3][CH2:4]3)=[CH:12][N:11]=2)[C:16](=[O:23])[N:17]([CH3:22])[N:18]=1

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 592164744-Bromo-6-chloro-2-methyl-2,3-dihydropyridazin-3-oneHCID 667422585-Cyclobutylaminomethyl-pyrazin-2-ylamine

생성물 1

HCID 667421676-Chloro-4-(5-cyclobutylaminomethyl-pyrazin-2-ylamino)-2-methyl-2H-pyridazin-3-one수율 39.1%

시약·촉매·용매 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladium촉매HCID 312751,4-Dioxane용매

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온도
105 °C

실험 절차

In a 15 mL microwave reaction vial was added a solution of 5-((cyclobutylamino)methyl)pyrazin-2-amine (280 mg, 1.57 mmol, Eq: 1.00) in dioxane (7 ml) under argon bubbling. To the solution was added 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (456 mg, 2.04 mmol, Eq: 1.3), Cs2CO3 (1.3 g, 3.99 mmol, Eq: 2.54), xantphos (136 mg, 236 mmol, Eq: 0.15) and bis(dibenzylideneacetone)palladium (67.7 mg, 118 μmol, Eq: 0.075). The reaction tube was sealed and heated in oil bath at 105° C. (bath temp) for 7 hrs then stirred at room temperature overnight. The crude reaction mixture was filtered and the solid was washed with dioxane (20 mL) and DCM (5 mL). The combined filtrate and washes were concentrated and absorbed on silica gel. The mixture was purified by LC chromatography (silica gel, 60 g) and eluted with 0-10% (10% NH4OH in MeOH) in ( 1/1) EtOAc/Heptane to afford 197 mg (39%) of the title compound.

후처리

  1. customIn a 15 mL microwave reaction
  2. customThe reaction tube was sealed
  3. customThe crude reaction mixture
  4. filtrationwas filtered
  5. washthe solid was washed with dioxane (20 mL) and DCM (5 mL)
  6. concentrationThe combined filtrate and washes were concentrated
  7. customabsorbed on silica gel
  8. customThe mixture was purified by LC chromatography (silica gel, 60 g)
  9. washeluted with 0-10% (10% NH4OH in MeOH) in ( 1/1) EtOAc/Heptane

출처 및 근거

ORD 기록
ord-f0f44cb0c5694589b204fbc573dbfd63
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08481540B2

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