2-Methyltetrahydrofuran → (3-Amino-2,6-difluorophenyl)(5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)methanone

HRID 1747253Notes

Reaction equation

HRID 1747253 reaction equation
CC1CCCO1.[Br:7][C:8]1[CH:9]=[C:10]2[C:16]([C:17]([C:19]3[C:24]([F:25])=[CH:23][CH:22]=[C:21]([N+:26]([O-])=O)[C:20]=3[F:29])=[O:18])=[CH:15][NH:14][C:11]2=[N:12][CH:13]=1.[Sn](Cl)Cl>>[NH2:26][C:21]1[C:20]([F:29])=[C:19]([C:17]([C:16]2[C:10]3[C:11](=[N:12][CH:13]=[C:8]([Br:7])[CH:9]=3)[NH:14][CH:15]=2)=[O:18])[C:24]([F:25])=[CH:23][CH:22]=1

Participants

4

Reactant 3

HCID 73012-MethyltetrahydrofuranHCID 24479Stannous ChlorideHCID 58087159(5-Bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)(2,6-difluoro-3-nitrophenyl)methanone

Product 1

HCID 58368727(3-Amino-2,6-difluorophenyl)(5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)methanoneYield 96.65%

Conditions

Temperature
60 °C

Procedure

A 50-liter flask was added 2-methyl-tetrahydrofuran (2-methyl-THF) (36 L), compound 3 (2.85 kg, 7.455 mol) and tin(II) chloride (5.03 kg, 22.365 mol). The mixture was heated to 60° C. Upon completion, the reaction was quenched with an aqueous potassium carbonate solution (20%). The resulting mixture was filtered with celite and the solid residue was washed with 2-methyl-THF and tetrahydrofuran (THF). The filtrate was washed with an aqueous NaCl solution (15 L, 10%) and the organic layer was separated. The organic layer was further washed with an aqueous NaCl solution (15 L, 20%) and concentrated on a rotovap to yield compound 4 (2.536 kg, 96.65% yield). MS (ESI): M+H+=353 and 354. 1H NMR (DMSO-d6, δ ppm): 5.22 (2H, s), 6.93 (2H, m), 8.12 (1H, s), 8.47 (1H, d J=2.3 Hz), 8.54 (1H, d J-1.6 Hz), 13.2 (1H, s).

Workup

  1. customUpon completion, the reaction was quenched with an aqueous potassium carbonate solution (20%)
  2. filtrationThe resulting mixture was filtered with celite
  3. washthe solid residue was washed with 2-methyl-THF and tetrahydrofuran (THF)
  4. washThe filtrate was washed with an aqueous NaCl solution (15 L, 10%)
  5. customthe organic layer was separated
  6. washThe organic layer was further washed with an aqueous NaCl solution (15 L, 20%)
  7. concentrationconcentrated on a rotovap

Sources & evidence

ORD record
ord-dd7a113e6ca44e8c81bc70b6b4f96990
Source dataset
uspto-grants-2015_10
Patent number
US09150570B2

Reaction notes

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