Potassium Phosphate, Tribasic → 4-[4-amino-2-(2,4-difluorophenoxy)-3-nitrophenyl]-6-methyl-1-[(4-methylphenyl)sulfonyl]-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one

HRID 1056935ノート

反応式

HRID 1056935 の反応式
[CH3:1][N:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[C:5]2[CH:17]=[CH:18][N:19]([S:20]([C:23]3[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][CH:24]=3)(=[O:22])=[O:21])[C:4]=2[C:3]1=[O:30].Br[C:32]1[CH:38]=[CH:37][C:35]([NH2:36])=[C:34]([N+:39]([O-:41])=[O:40])[C:33]=1[O:42][C:43]1[CH:48]=[CH:47][C:46]([F:49])=[CH:45][C:44]=1[F:50].P([O-])([O-])([O-])=O.[K+].[K+].[K+].CC12CC3(C)OC(C)(CC(C)(O3)O1)P2C1C=CC=CC=1>O1CCOCC1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH2:36][C:35]1[CH:37]=[CH:38][C:32]([C:6]2[C:5]3[CH:17]=[CH:18][N:19]([S:20]([C:23]4[CH:24]=[CH:25][C:26]([CH3:29])=[CH:27][CH:28]=4)(=[O:21])=[O:22])[C:4]=3[C:3](=[O:30])[N:2]([CH3:1])[CH:7]=2)=[C:33]([O:42][C:43]2[CH:48]=[CH:47][C:46]([F:49])=[CH:45][C:44]=2[F:50])[C:34]=1[N+:39]([O-:41])=[O:40]

参加物

8

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 534277901,3,5,7-Tetramethyl-6-phenyl-2,4,8-trioxa-6-phosphaadamantaneHCID 867210626-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-pyrrolo[2,3-c]pyridin-7(6H)-oneHCID 1180939204-Bromo-3-(2,4-difluorophenoxy)-2-nitroaniline

生成物 1

HCID 1180937554-[4-amino-2-(2,4-difluorophenoxy)-3-nitrophenyl]-6-methyl-1-[(4-methylphenyl)sulfonyl]-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one収率 47.7%

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

A suspension of 6-methyl-1-[(4-methylphenyl)sulfonyl]-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.17 g, 0.40 mmol), 4-bromo-3-(2,4-difluorophenoxy)-2-nitroaniline (0.14 g, 0.40 mmol), potassium phosphate (0.22 g, 1.0 mmol), tris(dibenzylideneacetone)dipalladium (0) (0.01 g, 0.01 mmol), and 1,3,5,7-tetramethyl-8-phenyl-2,4,6-trioxa-8-phosphatricyclo[3.3.1.13,7]decane (0.0139 g, 0.0475 mmol) in 1,4-dioxane (4 mL) and water (0.9 mL) was degassed with nitrogen for 5 min and stirred at 80° C. for 2 h. The reaction mixture was diluted with ethyl acetate and water. The organic layer was separated, washed with brine, dried with magnesium sulfate, filtered, and concentrated to give a crude residue. Purification by flash column chromatography (100% hexanes to 40% EtOAc/hexanes) gave the desired product (108 mg, 23%) as a brown oil. LCMS calculated for C27H21F2N4O6S (M+H)+: m/z=567.1. found: 567.1.

後処理

  1. customwas degassed with nitrogen for 5 min
  2. additionThe reaction mixture was diluted with ethyl acetate and water
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried with magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a crude residue
  9. customPurification by flash column chromatography (100% hexanes to 40% EtOAc/hexanes)

出典と根拠

ORDレコード
ord-21036e9558d242d4a6406552d0398e4e
出典データセット
uspto-grants-2016_07
特許番号
US09399640B2

反応ノート

読み込み中…