Water → tert-butyl 3-(4-bromo-3-(5-fluoro-1-methylindolin-6-yl)-1H-pyrrolo[2,3-b]pyridin-1-yl)azetidine-1-carboxylate

HRID 331015ノート

反応式

HRID 331015 の反応式
[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]3[CH2:15][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:13]3)[CH:9]=[C:10](I)[C:3]=12.Cl.[F:24][C:25]1[CH:26]=[C:27]2[C:31](=[CH:32][C:33]=1B1OC(C)(C)C(C)(C)O1)[N:30]([CH3:43])[CH2:29][CH2:28]2.C(=O)([O-])[O-].[Na+].[Na+].O>COCCOC.CO.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]3[CH2:15][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:13]3)[CH:9]=[C:10]([C:33]3[CH:32]=[C:31]4[C:27]([CH2:28][CH2:29][N:30]4[CH3:43])=[CH:26][C:25]=3[F:24])[C:3]=12

参加物

8

反応物 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 86720286tert-butyl 3-(4-bromo-3-iodo-1H-pyrrolo[2,3-b]pyridin-1-yl)azetidine-1-carboxylateHCID 1317319925-Fluoro-1-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indoline, hydrochloride

生成物 1

HCID 71090156tert-butyl 3-(4-bromo-3-(5-fluoro-1-methylindolin-6-yl)-1H-pyrrolo[2,3-b]pyridin-1-yl)azetidine-1-carboxylate収率 67.8%

試薬・触媒・溶媒 3

HCID 178418476HCID 178418476、化合物触媒HCID 887Methanol溶媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
60 °C

実験手順

To a mixture of tert-butyl 3-(4-bromo-3-iodo-1H-pyrrolo[2,3-b]pyridin-1-yl)azetidine-1-carboxylate (D31) (118 mg, 0.247 mmol), 5-fluoro-1-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indoline, hydrochloride (85 mg, 0.271 mmol) in DME (2 mL) and MeOH (0.222 mL) was added bis(triphenylphosphine)palladium(II) chloride (17.32 mg, 0.025 mmol) and 2M sodium carbonate aq. solution (1.234 mL, 2.468 mmol). The mixture was stirred at 60° C. for 1 hour. The mixture was cooled to RT. Water (30 mL) was added and was extracted with ethyl acetate (3×50 mL). The combined organics were dried over magnesium sulfate, filtered and solvent removed in vacuo to give a residue which was purified on normal phase chromatography eluting with ethyl acetate in cyclohexane (0-50%) to give the title compound (84 mg). LCMS (A): m/z (M+H)+ 501/503, C24H26BrFN4O2 requires 500/502 (acidic).

後処理

  1. temperatureThe mixture was cooled to RT
  2. extractionwas extracted with ethyl acetate (3×50 mL)
  3. dry with materialThe combined organics were dried over magnesium sulfate
  4. filtrationfiltered
  5. customsolvent removed in vacuo
  6. customto give a residue which
  7. customwas purified on normal phase chromatography
  8. washeluting with ethyl acetate in cyclohexane (0-50%)

出典と根拠

ORDレコード
ord-a727b0d05358407b8d83222977f9d595
出典データセット
uspto-grants-2014_11
特許番号
US08877742B2

反応ノート

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