Potassium Phosphate, Tribasic → 2-[(5-bromo-2-chloro-4-pyridinyl)amino]-N-methoxyBenzamide

HRID 62512ノート

反応式

HRID 62512 の反応式
[Br:1][C:2]1[C:3](I)=[CH:4][C:5]([Cl:8])=[N:6][CH:7]=1.[NH2:10][C:11]1[CH:21]=[CH:20][CH:19]=[CH:18][C:12]=1[C:13]([NH:15][O:16][CH3:17])=[O:14].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1C=CC(P(C2C(OC3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=CC=3)=CC=CC=2)C2C=CC=CC=2)=CC=1>CC([O-])=O.CC([O-])=O.[Pd+2].O1CCOCC1>[Br:1][C:2]1[C:3]([NH:10][C:11]2[CH:21]=[CH:20][CH:19]=[CH:18][C:12]=2[C:13]([NH:15][O:16][CH3:17])=[O:14])=[CH:4][C:5]([Cl:8])=[N:6][CH:7]=1

参加物

7

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 4285986Bis[2-(diphenylphosphino)phenyl] etherHCID 123927072-Amino-N-methoxybenzamideHCID 218651405-Bromo-2-chloro-4-iodopyridine

生成物 1

HCID 575169052-[(5-bromo-2-chloro-4-pyridinyl)amino]-N-methoxyBenzamide

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 312751,4-Dioxane溶媒

実験手順

A mixture of 5-bromo-2-chloro-4-iodo-pyridine (5 g, 15.72 mmole, 1 eq), 2-amino-N-methoxy-benzamide (2.61 g, 15.72 mmole, 1 eq) and K3PO4 (8.34 g, 39.3 mmole, 2.5 eq), and 1,4-dioxane (30 mL) was degassed with N2 for 1 h. To this was added DPEPhos (0.67 g, 1.25 mmole, 0.08 eq) and Pd(OAc)2 (0.07 g, 0.31 mmole, 0.02 eq) and this mixture was degassed again with N2 for 30 min. The resulting mixture was refluxed for overnight. After completion of reaction, solvent was removed under reduced pressure and residue was diluted with water (100 mL) and extracted with 5% MeOH-DCM (3×100 mL). Combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure to give a crude compound. It was purified by column chromatography over silica gel (60-120 mesh) using 20% Ethyl acetate-hexane as the eluant to yield the title compound as off white solid (3.5 g, 62%). 1H-NMR (400 MHz, DMSO-d6): δ 3.56 (s, 3H), 6.88-6.98 (m, 1H), 7.08 (s, 1H), 7.17-7.25 (m, 1H), 7.26-7.35 (m, 1H), 7.82-7.90 (m, 1H), 8.23 (s, 1H), 12.86 (brs, 1H). LC-MS [M+H]+=356.30.

後処理

  1. customwas degassed with N2 for 1 h
  2. customthis mixture was degassed again with N2 for 30 min
  3. temperatureThe resulting mixture was refluxed for overnight
  4. customAfter completion of reaction, solvent
  5. customwas removed under reduced pressure and residue
  6. additionwas diluted with water (100 mL)
  7. extractionextracted with 5% MeOH-DCM (3×100 mL)
  8. dry with materialCombined organic layers were dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customto give a crude compound
  12. customIt was purified by column chromatography over silica gel (60-120 mesh)

出典と根拠

ORDレコード
ord-86b18335043145188c37a47d393fd940
出典データセット
uspto-grants-2016_09
特許番号
US09446034B2

反応ノート

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