Sodium Hydroxide → 5-Bromo-3-[(S)-1-(2,6-dichloro-3-fluorophenyl)ethyl]-1H-pyrrolo[2,3-b]pyridine

HRID 2046909Notes

Reaction equation

HRID 2046909 reaction equation
C1C2C(COC(=O)N[C@H](C([N:25]3[C:29]4=[N:30][CH:31]=[C:32]([Br:34])[CH:33]=[C:28]4[C:27]([C@@H:35]([C:37]4[C:42]([Cl:43])=[CH:41][CH:40]=[C:39]([F:44])[C:38]=4[Cl:45])[CH3:36])=[CH:26]3)=O)CC(C)C)C3C(=CC=CC=3)C=2C=CC=1.[OH-].[Na+]>C1COCC1>[Br:34][C:32]1[CH:33]=[C:28]2[C:27]([C@@H:35]([C:37]3[C:42]([Cl:43])=[CH:41][CH:40]=[C:39]([F:44])[C:38]=3[Cl:45])[CH3:36])=[CH:26][NH:25][C:29]2=[N:30][CH:31]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 58431443HCID 58431443, compound

Product 1

HCID 584314455-Bromo-3-[(S)-1-(2,6-dichloro-3-fluorophenyl)ethyl]-1H-pyrrolo[2,3-b]pyridine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ((S)-1-{5-Bromo-3-[(S)-1-(2,6-dichloro-3-fluorophenyl)ethyl]pyrrolo[2,3-b]pyridine-1-carbonyl}-3-methylbutyl)-carbamic acid 9H-fluoren-9-ylmethyl ester (722 mg, 1.00 mmol) in THF (20 mL) was added NaOH (5N in H2O, 1 mL) at 0° C. with stirring. After stirring for 1 h at that temperature, solvents were removed under reduced pressure to give a residue which was then purified by flash chromatography (eluent: Hexane/ethyl acetate: 75/25, v/v) to give the title compound. 1H NMR and LCMS data match with the data for the racemic compound. Optical rotation: [α]25D=−112.8° (c=1.0, MeOH); [α]25D=−152.6° (c=1.0, CH2Cl2). HPLC (Chiralcel OD-RH, solvent 60:40 acetonitrile/water isocratic, flow rate 0.5 mL/min, column temperature 30° C., UV detection at 220 nm): tR=28.0 min. C15H10BrCl2FN2 (388.07): Calculated: C, 46.43; H, 2.60; Br, 20.59; Cl, 18.27; F, 4.90; N, 7.22. found C, 46.36; H, 2.49; Br, 20.38; Cl, 18.31; F, 4.79; N, 7.09. A crystal structure of Example 85, prepared using this material, bound to cMet confirmed the absolute configuration as shown.

Workup

  1. stirringAfter stirring for 1 h at that temperature, solvents
  2. customwere removed under reduced pressure
  3. customto give a residue which
  4. customwas then purified by flash chromatography (eluent

Sources & evidence

ORD record
ord-cd5dd3dee4144b23af11637be2b6467c
Source dataset
uspto-grants-2013_11
Patent number
US08592448B2

Reaction notes

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