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Triethylamine → N-(5-(6-(4-(N'-hydroxycarbamimidoyl)-2-(trifluoromethyl)phenyl)imidazo[1,2-b]pyridazin-2-yl)-2-methylphenyl)pivalamide

HRID 539800
ノート
印刷プレビュー

反応式

HRID 539800 の反応式
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[CH:11][C:12]3[N:13]([CH:15]=[C:16]([C:18]4[CH:19]=[CH:20][C:21]([CH3:31])=[C:22]([NH:24][C:25](=[O:30])[C:26]([CH3:29])([CH3:28])[CH3:27])[CH:23]=4)[N:17]=3)[N:14]=2)=[C:5]([C:32]([F:35])([F:34])[F:33])[CH:4]=1)#[N:2].Cl.[NH2:37][OH:38].CCN(CC)CC>C(O)C>[OH:38][N:37]=[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[CH:11][C:12]3[N:13]([CH:15]=[C:16]([C:18]4[CH:19]=[CH:20][C:21]([CH3:31])=[C:22]([NH:24][C:25](=[O:30])[C:26]([CH3:29])([CH3:28])[CH3:27])[CH:23]=4)[N:17]=3)[N:14]=2)=[C:5]([C:32]([F:33])([F:35])[F:34])[CH:4]=1)[NH2:2]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 8471TriethylamineHCID 443297Hydroxyamine hydrochlorideHCID 57406897N-(5-(6-(4-cyano-2-(trifluoromethyl)phenyl)imidazo[1,2-b]pyridazin-2-yl)-2-methylphenyl)pivalamide

生成物 1

HCID 136332422N-(5-(6-(4-(N'-hydroxycarbamimidoyl)-2-(trifluoromethyl)phenyl)imidazo[1,2-b]pyridazin-2-yl)-2-methylphenyl)pivalamide収率 81.8%

試薬・触媒・溶媒 1

HCID 702
Ethanol
溶媒

反応条件

温度
80 °C

実験手順

A 500-mL flask is charged with N-(5-(6-(4-cyano-2-(trifluoromethyl)phenyl)imidazo[1,2-b]pyridazin-2-yl)-2-methylphenyl)pivalamide (7.496 g, 0.0157 mol), hydroxylamine hydrochloride (6.55 g, 0.0942 mol), Et3N (15.32 mL, 0.1099 mol), ethanol (82.5 mL) and the resulting mixture is stirred for 2 hours at 80° C. The mixture is concentrated onto celite and purified by silica gel chromatography (eluted by 0 to 100% of 10:1 EtOAc:MeOH in CH2Cl2). The isolated solid material (over 20 g) contains triethylamine and hydroxylamine salts, and the salts stay even after attempted recrystallization with isopropanol. This solid product is then added to a stirred mixture of saturated aqueous NaHCO3 and EtOAc. Solid suspension is collected by filtration. The liquid portion is back extracted with EtOAc and the organic layers are combined, dried with Na2SO4, concentrated to afford additional solid product. The combined solid product is dried on a lyophilizer overnight, recrystallized from hot Isopropanol to afford the desired title product (6.56 g). LCMS (m/z)=511.6 [M+H]+, tR=2.49 min.

後処理

  1. concentrationThe mixture is concentrated onto celite
  2. custompurified by silica gel chromatography (eluted by 0 to 100% of 10:1 EtOAc:MeOH in CH2Cl2)
  3. customrecrystallization with isopropanol
  4. additionThis solid product is then added to a stirred mixture of saturated aqueous NaHCO3 and EtOAc
  5. filtrationSolid suspension is collected by filtration
  6. extractionThe liquid portion is back extracted with EtOAc
  7. dry with materialdried with Na2SO4
  8. concentrationconcentrated
  9. customto afford additional solid product
  10. customThe combined solid product is dried on a lyophilizer overnight
  11. customrecrystallized from hot Isopropanol

出典と根拠

ORDレコード
ord-e3b1332fe8ca4e5e9b9461ad42e2132d
出典データセット
uspto-grants-2014_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08871767B2

反応ノート

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