Potassium Phosphate, Tribasic → 5-(2,4-Difluorophenoxy)-6-{6-methyl-1-[(4-methylphenyl)sulfonyl]-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl}-1,3-dihydro-2H-benzimidazol-2-one

HRID 629296노트

반응식

HRID 629296 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[C:41]([O:42][C:43]2[CH:48]=[CH:47][C:46]([F:49])=[CH:45][C:44]=2[F:50])=[CH:40][C:35]2[NH:36][C:37](=[O:39])[NH:38][C:34]=2[CH:33]=1.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]>[F:50][C:44]1[CH:45]=[C:46]([F:49])[CH:47]=[CH:48][C:43]=1[O:42][C:41]1[C:32]([C:6]2[C:5]3[CH:17]=[CH:18][N:19]([S:20]([C:23]4[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][CH:24]=4)(=[O:22])=[O:21])[C:4]=3[C:3](=[O:30])[N:2]([CH3:1])[CH:7]=2)=[CH:33][C:34]2[NH:38][C:37](=[O:39])[NH:36][C:35]=2[CH:40]=1

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 1180936705-Bromo-6-(2,4-difluorophenoxy)-1,3-dihydro-2H-benzimidazol-2-one

생성물 1

HCID 1180936395-(2,4-Difluorophenoxy)-6-{6-methyl-1-[(4-methylphenyl)sulfonyl]-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl}-1,3-dihydro-2H-benzimidazol-2-one수율 21.3%

시약·촉매·용매 3

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

반응 조건

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 (85.0 mg, 0.20 mmol), 5-bromo-6-(2,4-difluorophenoxy)-1,3-dihydro-2H-benzimidazol-2-one (74.5 mg, 0.218 mmol), potassium phosphate (0.10 g, 0.50 mmol), tris(dibenzylideneacetone)dipalladium (O) (5.0 mg, 0.006 mmol), and 1,3,5,7-tetramethyl-8-phenyl-2,4,6-trioxa-8-phosphatricyclo[3.3.1.13,7]decane (6.8 g, 0.0232 mmol) in 1,4-dioxane (2 mL) and water (0.4 mL) was degassed with nitrogen for 5 min and stirred at 80° C. for 1 h. The reaction mixture was diluted with ethyl acetate and water and filtered over celite. The organic layer was separated, washed with brine, dried with magnesium sulfate, filtered, and concentrated to give a crude residue. Purification via preparative LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% trifluoroacetic acid, at flow rate of 60 mL/min) gave the desired product (24 mg, 18%) as an off-white foam. LCMS calculated for C28H21F2N4O5S (M+H)+: m/z=563.1. found: 563.1.

후처리

  1. customwas degassed with nitrogen for 5 min
  2. additionThe reaction mixture was diluted with ethyl acetate and water
  3. filtrationfiltered over celite
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried with magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a crude residue
  10. customPurification via preparative LCMS (XBridge C18 column
  11. washeluting with a gradient of acetonitrile/water containing 0.1% trifluoroacetic acid, at flow rate of 60 mL/min)

출처 및 근거

ORD 기록
ord-66162bd552c743e98e6734d5956726f6
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09315501B2

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