(E)-N'-Hydroxyacetimidamide → 4-((6-(3-Chloro-4-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methoxy)-7-methoxyquinoline

HRID 219076ノート

反応式

HRID 219076 の反応式
CN(C(O[N:9]1N=N[C:11]2C=CC=[N:15][C:10]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Cl:25][C:26]1[CH:34]=[C:33]([C:35]2[CH:36]=[CH:37][C:38]3[N:39]([C:41]([CH2:44][O:45][C:46]4[C:55]5[C:50](=[CH:51][C:52]([O:56][CH3:57])=[CH:53][CH:54]=5)[N:49]=[CH:48][CH:47]=4)=[N:42][N:43]=3)[N:40]=2)[CH:32]=[CH:31][C:27]=1[C:28](O)=[O:29].O/N=C(\N)/C>CN(C=O)C.O>[Cl:25][C:26]1[CH:34]=[C:33]([C:35]2[CH:36]=[CH:37][C:38]3[N:39]([C:41]([CH2:44][O:45][C:46]4[C:55]5[C:50](=[CH:51][C:52]([O:56][CH3:57])=[CH:53][CH:54]=5)[N:49]=[CH:48][CH:47]=4)=[N:42][N:43]=3)[N:40]=2)[CH:32]=[CH:31][C:27]=1[C:28]1[O:29][N:15]=[C:10]([CH3:11])[N:9]=1

参加物

6

反応物 3

HCID 5487681(E)-N'-HydroxyacetimidamideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 250657522-Chloro-4-(3-((7-methoxyquinolin-4-yloxy)methyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)benzoic acid

生成物 1

HCID 250659724-((6-(3-Chloro-4-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methoxy)-7-methoxyquinoline

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒2 回

反応条件

温度
150 °C

実験手順

HATU (0.370 g, 0.974 mmol) and 2-chloro-4-(3-((7-methoxyquinolin-4-yloxy)methyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)benzoic acid (0.300 g, 0.650 mmol) were taken up in DMF (5 mL). Added Hunig'sBase (0.339 ml, 1.95 mmol). Stirred for 10 min. Added (Z)-N′-hydroxyacetamidine (0.289 g, 3.90 mmol). Stirred for an additional 30 min. Removed DMF in vacuo. Suspended in water. Isolated product by filtration. The resulting solid was allowed to try under vacuum. Split into 3 portions and separately took up in dioxane (4 mL) in a microwave tube and heated for 12 min at 150° C. Combined all 3 reactions. Concentrated. Purified on RPHPLC. Took fractions containing product and made basic with 9% sodium carbonate. Removed volatiles in vacuo. Product crashed out and was isolated by filtration. MS m/z=500.0 [M+1]+. Calc'd for C25H18ClN7O3: 499.1.

後処理

  1. stirringStirred for an additional 30 min
  2. filtrationIsolated product by filtration
  3. customSplit into 3 portions
  4. customseparately took up in dioxane (4 mL) in a microwave tube
  5. concentrationConcentrated
  6. customPurified on RPHPLC
  7. additionTook fractions containing product
  8. customwas isolated by filtration

出典と根拠

ORDレコード
ord-71094a44fad04dc98ee2da1f0aee47a4
出典データセット
uspto-grants-2012_06
特許番号
US08198448B2

反応ノート

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