Water → 3-[[5-cyano-3-fluoro-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pyridyl]amino]-4,4-dimethyl-hexanoic acid

HRID 2171920Notes

Reaction equation

HRID 2171920 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([F:42])[C:6]([NH:29][CH:30]([C:37]([CH3:41])([CH3:40])[CH2:38][CH3:39])[CH2:31][C:32]([O:34]CC)=[O:33])=[N:7][C:8]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([F:18])[CH:16]=2)[N:11](S(C2C=CC(C)=CC=2)(=O)=O)[CH:10]=1)#[N:2].[Li+].[OH-].O.C(OCC)(=O)C>C1COCC1>[C:1]([C:3]1[CH:4]=[C:5]([F:42])[C:6]([NH:29][CH:30]([C:37]([CH3:41])([CH3:40])[CH2:38][CH3:39])[CH2:31][C:32]([OH:34])=[O:33])=[N:7][C:8]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([F:18])[CH:16]=2)[NH:11][CH:10]=1)#[N:2]

Participants

6

Reactant 4

HCID 962WaterHCID 3939Lithium HydroxideHCID 8857Ethyl AcetateHCID 71251266Ethyl 3-[[5-cyano-3-fluoro-6-[5-fluoro-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridin-3-yl]-2-pyridyl]amino]-4,4-dimethyl-hexanoate2×

Product 1

HCID 712512653-[[5-cyano-3-fluoro-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-pyridyl]amino]-4,4-dimethyl-hexanoic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

Ethyl 3-[[5-cyano-3-fluoro-6-[5-fluoro-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridin-3-yl]-2-pyridyl]amino]-4,4-dimethyl-hexanoate, 159a, (0.27 g, 0.45 mmol) was dissolved in THF (7 mL) and treated with LiOH (4.50 mL of 1 M, 4.50 mmol). The reaction mixture was heated to 70° C. for 10 hours. After cooling to room temperature, water (20 mL) and ethyl acetate (20 mL) were added and the layers were separated. The aqueous layer was brought to a neutral pH by addition of 1N HCl, and the resulting precipitate was collected by filtration, washed with water and concentrated in vacuo to provide 77 mg of the desired product: 1H NMR (400 MHz, DMSO-d6) δ 12.37 (s, 1H), 12.12 (s, 1H), 8.75 (d, J=9.9 Hz, 1H), 8.32 (s, 2H), 7.83 (d, J=11.4 Hz, 1H), 7.48 (d, J=9.5 Hz, 1H), 5.00 (t, J=9.1 Hz, 1H), 2.71-2.54 (m, 2H), 1.30 (d, J=7.4 Hz, 2H), 0.80 (t, J=18.7 Hz, 9H); LCMS Gradient 10-90%, 0.1% formic acid, 5 minutes, C18/ACN, Retention Time=3.14 minutes (M+H) 414.31.

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe layers were separated
  3. additionThe aqueous layer was brought to a neutral pH by addition of 1N HCl
  4. filtrationthe resulting precipitate was collected by filtration
  5. washwashed with water
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c16bdd2491eb4d45955799625d9a8c13
Source dataset
uspto-grants-2015_06
Patent number
US09051319B2

Reaction notes

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