Cesium carbonate → 6-chloro-4-(5-(4-isopropylpiperazin-1-yl)pyridin-2-ylamino)-2-methylpyridazin-3(2H)-one

HRID 449610ノート

反応式

HRID 449610 の反応式
[CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:11]=[CH:12][C:13]([NH2:16])=[N:14][CH:15]=2)[CH2:6][CH2:5]1)([CH3:3])[CH3:2].Br[C:18]1[C:19](=[O:26])[N:20]([CH3:25])[N:21]=[C:22]([Cl:24])[CH:23]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[Cl:24][C:22]1[CH:23]=[C:18]([NH:16][C:13]2[CH:12]=[CH:11][C:10]([N:7]3[CH2:6][CH2:5][N:4]([CH:1]([CH3:3])[CH3:2])[CH2:9][CH2:8]3)=[CH:15][N:14]=2)[C:19](=[O:26])[N:20]([CH3:25])[N:21]=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 434619445-(4-(Propan-2-yl)piperazin-1-yl)pyridin-2-amineHCID 592164744-Bromo-6-chloro-2-methyl-2,3-dihydropyridazin-3-one

生成物 1

HCID 667422216-chloro-4-(5-(4-isopropylpiperazin-1-yl)pyridin-2-ylamino)-2-methylpyridazin-3(2H)-one収率 83%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

In a 50 mL round-bottomed flask, 5-(4-isopropylpiperazin-1-yl)pyridin-2-amine (200 mg, 908 μl mmol, Eq: 1.00), 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (243 mg, 1.09 mmol, Eq: 1.2) and cesium carbonate (887 mg, 2.72 mmol, Eq: 3) were combined with dioxane (20 ml) to give a orange suspension. 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene (78.8 mg, 136 mmol, eq: 0.15) was added. Tris(dibenzylideneacetone)dipalladium(0) (41.6 mg, 45.4 μmol, Eq: 0.05) was added. The solution was degassed with Ar for 10 min. The solution was heated at 95-105° C. for 48 h. The solution was diluted with 200 ml DCM. MgSO4 was added and the suspension stirred for 10 min. The solid was filtered and washed several times with DCM. The organics were concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 40 g, 50% to 100% EtOAc/hexanes gradient) to give 6-chloro-4-(5-(4-isopropylpiperazin-1-yl)pyridin-2-ylamino)-2-methylpyridazin-3(2H)-one (273 mg, 83%). LC/MS-ESI observed [M+H]+ 363.

後処理

  1. customto give a orange suspension
  2. customThe solution was degassed with Ar for 10 min
  3. additionThe solution was diluted with 200 ml DCM
  4. additionMgSO4 was added
  5. filtrationThe solid was filtered
  6. washwashed several times with DCM
  7. concentrationThe organics were concentrated in vacuo
  8. customThe crude material was purified by flash chromatography (silica gel, 40 g, 50% to 100% EtOAc/hexanes gradient)

出典と根拠

ORDレコード
ord-e5ecc1e8973048e08148d74f3f2110c5
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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