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

HRID 449638ノート

反応式

HRID 449638 の反応式
[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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladium触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
105 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-f0f44cb0c5694589b204fbc573dbfd63
出典データセット
uspto-grants-2013_07
特許番号
US08481540B2

反応ノート

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