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 1056935노트

반응식

HRID 1056935 반응식
[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]

참가 물질

8

반응물 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

생성물 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-one수율 47.7%

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 312751,4-Dioxane용매

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온도
80 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-21036e9558d242d4a6406552d0398e4e
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09399640B2

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