Potassium Phosphate, Tribasic → (4-{1-Methyl-5-[(5-methyl-1,2-oxazol-3-yl)amino]-6-oxo-1,6-dihydropyridin-3-yl}-2-{6-oxo-8-thia-4,5-diazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3-trien-5-yl}pyridin-3-yl)methyl Acetate

HRID 1412015ノート

反応式

HRID 1412015 の反応式
[C:1]([O:4][CH2:5][C:6]1[C:7]([N:21]2[C:33](=[O:34])[C:32]3[S:31][C:30]4[CH2:29][CH2:28][CH2:27][CH2:26][C:25]=4[C:24]=3[CH:23]=[N:22]2)=[N:8][CH:9]=[CH:10][C:11]=1B1OC(C)(C)C(C)(C)O1)(=[O:3])[CH3:2].Br[C:36]1[CH:37]=[C:38]([NH:44][C:45]2[CH:49]=[C:48]([CH3:50])[O:47][N:46]=2)[C:39](=[O:43])[N:40]([CH3:42])[CH:41]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C([O-])(=O)C.[Na+]>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].C(#N)C.O>[C:1]([O:4][CH2:5][C:6]1[C:7]([N:21]2[C:33](=[O:34])[C:32]3[S:31][C:30]4[CH2:29][CH2:28][CH2:27][CH2:26][C:25]=4[C:24]=3[CH:23]=[N:22]2)=[N:8][CH:9]=[CH:10][C:11]=1[C:36]1[CH:37]=[C:38]([NH:44][C:45]2[CH:49]=[C:48]([CH3:50])[O:47][N:46]=2)[C:39](=[O:43])[N:40]([CH3:42])[CH:41]=1)(=[O:3])[CH3:2]

参加物

8

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 592164565-Bromo-1-methyl-3-(5-methylisoxazol-3-ylamino)pyridin-2(1H)-oneHCID 86684536(2-{6-Oxo-8-thia-4,5-diazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3-trien-5-yl}-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)methyl acetate

生成物 1

HCID 86684535(4-{1-Methyl-5-[(5-methyl-1,2-oxazol-3-yl)amino]-6-oxo-1,6-dihydropyridin-3-yl}-2-{6-oxo-8-thia-4,5-diazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3-trien-5-yl}pyridin-3-yl)methyl Acetate収率 60.1%

試薬・触媒・溶媒 3

HCID 44119782Bis(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 50-mL round-bottomed flask equipped with a reflux condenser was charged with (2-{6-oxo-8-thia-4,5-diazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3-trien-5-yl}-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)methyl acetate 230i (150 mg, 0.31 mmol), 5-bromo-1-methyl-3-(5-methylisoxazol-3-ylamino)pyridine-2(1H)-one 283a (88 mg, 0.31 mmol), PdCl2(dppf) (24 mg, 0.031 mmol), K3PO4 (131 mg, 0.62 mmol), sodium acetate (61 mg, 0.62 mmol), water (0.2 mL), and acetonitrile (10 mL). The system was subjected to three cycles of vacuum/argon flush and stirred at 100° C. for 3 h. The reaction mixture was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure. The residue was partitioned between dichloromethane (20 mL) and water (10 mL). The organic layer was separated and the water layer was extracted with dichloromethane (2×20 mL). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The dark residue was purified by silica-gel column chromatography eluting with 30:1 dichloromethane/methanol to afford 291a (104 mg, 60%) as a yellow solid. MS-ESI: [M+H]+ 559.1

後処理

  1. customA 50-mL round-bottomed flask equipped with a reflux condenser
  2. customflush
  3. temperatureThe reaction mixture was cooled to room temperature
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customThe residue was partitioned between dichloromethane (20 mL) and water (10 mL)
  7. customThe organic layer was separated
  8. extractionthe water layer was extracted with dichloromethane (2×20 mL)
  9. dry with materialThe combined organic layer was dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe dark residue was purified by silica-gel column chromatography
  13. washeluting with 30:1 dichloromethane/methanol

出典と根拠

ORDレコード
ord-b4600cebf71741f0a213dc61abdda560
出典データセット
uspto-grants-2014_12
特許番号
US08921353B2

反応ノート

読み込み中…