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 331015Notes

Reaction equation

HRID 331015 reaction equation
[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

Participants

8

Reactant 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

Product 1

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

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 887MethanolSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
60 °C

Procedure

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).

Workup

  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%)

Sources & evidence

ORD record
ord-a727b0d05358407b8d83222977f9d595
Source dataset
uspto-grants-2014_11
Patent number
US08877742B2

Reaction notes

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