Potassium Phosphate, Tribasic → (S)-4-(1-Methyl-5-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)-pyridin-2-yl-amino)-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-6,7,8,9 tetrahydro-pyridazino[4,5-b]indolizin-2(1H)-yl)nicotinaldehyde

HRID 592818ノート

反応式

HRID 592818 の反応式
Cl[C:2]1[C:7]([CH:8]=[O:9])=[C:6]([N:10]2[C:22](=[O:23])[C:14]3[CH:15]=[C:16]4[N:21]([C:13]=3[CH:12]=[N:11]2)[CH2:20][CH2:19][CH2:18][CH2:17]4)[N:5]=[CH:4][CH:3]=1.[CH3:24][N:25]1[CH:30]=[C:29](B2OC(C)(C)C(C)(C)O2)[CH:28]=[C:27]([NH:40][C:41]2[CH:46]=[CH:45][C:44]([N:47]3[CH2:52][CH2:51][N:50]([CH:53]4[CH2:56][O:55][CH2:54]4)[CH2:49][C@@H:48]3[CH3:57])=[CH:43][N:42]=2)[C:26]1=[O:58].C([O-])(=O)C.[Na+].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O.C(#N)C>[CH3:24][N:25]1[C:26](=[O:58])[C:27]([NH:40][C:41]2[CH:46]=[CH:45][C:44]([N:47]3[CH2:52][CH2:51][N:50]([CH:53]4[CH2:54][O:55][CH2:56]4)[CH2:49][C@@H:48]3[CH3:57])=[CH:43][N:42]=2)=[CH:28][C:29]([C:2]2[C:7]([CH:8]=[O:9])=[C:6]([N:10]3[C:22](=[O:23])[C:14]4[CH:15]=[C:16]5[N:21]([C:13]=4[CH:12]=[N:11]3)[CH2:20][CH2:19][CH2:18][CH2:17]5)[N:5]=[CH:4][CH:3]=2)=[CH:30]1

参加物

8

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 866837011-methyl-3-((5-((2S)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)amino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-oneHCID 866843544-Chloro-2-(1-oxo-6,7,8,9-tetrahydropyridazino[4,5-b]indolizin-2(1H)-yl)nicotinaldehyde

生成物 1

HCID 86684355(S)-4-(1-Methyl-5-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)-pyridin-2-yl-amino)-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-6,7,8,9 tetrahydro-pyridazino[4,5-b]indolizin-2(1H)-yl)nicotinaldehyde収率 53%

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒HCID 6342Acetonitrile溶媒

反応条件

温度
100 °C

実験手順

A 100-mL round-bottomed flask equipped with a reflux condenser was charged with 193f (200 mg, 0.61 mmol), 191j (293 mg, 0.60 mmol), sodium acetate (98 mg, 1.2 mmol), K3PO4 (254 mg, 1.2 mmol), PdCl2(dppf) (50 mg, 0.060 mmol), acetonitrile (25 mL), and water (1 mL). After bubbling nitrogen through the mixture for 30 minutes, it was heated at 100° C. for 3 hours. The mixture was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by silica-gel column chromatography eluting with 25:1 methylene chloride/methanol to afford 193g (206 mg, 53%) as a brown solid. MS-ESI: [M+H]+ 648.3.

後処理

  1. customA 100-mL round-bottomed flask equipped with a reflux condenser
  2. customAfter bubbling nitrogen through the mixture for 30 minutes
  3. temperatureThe mixture was cooled to room temperature
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe residue was purified by silica-gel column chromatography
  7. washeluting with 25:1 methylene chloride/methanol

出典と根拠

ORDレコード
ord-85be1d45b7594c01b0c953b7a6c010c5
出典データセット
uspto-grants-2016_01
特許番号
US09238655B2

反応ノート

読み込み中…