Methanol → 2-(4-{6-Amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)ethoxy]-pyridin-3-yl}-pyrazol-1-yl)-propionic acid

HRID 1627580Notes

Reaction equation

HRID 1627580 reaction equation
[Li+].[OH-].C[O:4][C:5](=[O:32])[CH:6]([N:8]1[CH:12]=[C:11]([C:13]2[CH:14]=[N:15][C:16]([NH2:31])=[C:17]([O:19][CH:20]([C:22]3[C:27]([Cl:28])=[CH:26][CH:25]=[C:24]([F:29])[C:23]=3[Cl:30])[CH3:21])[CH:18]=2)[CH:10]=[N:9]1)[CH3:7].C1COCC1.CO>O>[NH2:31][C:16]1[N:15]=[CH:14][C:13]([C:11]2[CH:10]=[N:9][N:8]([CH:6]([CH3:7])[C:5]([OH:32])=[O:4])[CH:12]=2)=[CH:18][C:17]=1[O:19][CH:20]([C:22]1[C:27]([Cl:28])=[CH:26][CH:25]=[C:24]([F:29])[C:23]=1[Cl:30])[CH3:21]

Participants

6

Reactant 4

HCID 887MethanolHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 67084570HCID 67084570, compound

Product 1

HCID 586591442-(4-{6-Amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)ethoxy]-pyridin-3-yl}-pyrazol-1-yl)-propionic acidYield 104.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A solution of LiOH (34 mg, 1.4 mmol) in water (0.4 mL) was added to a solution of 2-(4-{6-Amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-pyrazol-1-yl)-propionic acid methyl ester (70 mg, 0.15 mmol) in a mixture THF (1.5 mL) and MeOH (0.4 mL). After stirring overnight, the reaction was partitioned between dichloromethane and half-saturated brine. A small amount of ethanol was added and the pH was adjusted to 7 with 1 M HCl. The phases were separated and the aqueous phase was extracted with dichloromethane. The combined organic phases were dried over Na2SO4, filtered and concentrated by rotary evaporation to give 2-(4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)ethoxy]-pyridin-3-yl}-pyrazol-1-yl)-propionic acid (69 mg, 100%).

Workup

  1. customthe reaction was partitioned between dichloromethane and half-saturated brine
  2. additionA small amount of ethanol was added
  3. customThe phases were separated
  4. extractionthe aqueous phase was extracted with dichloromethane
  5. dry with materialThe combined organic phases were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated by rotary evaporation

Sources & evidence

ORD record
ord-0985c0d562394d27a3720f6d4244be93
Source dataset
uspto-grants-2014_07
Patent number
US08785632B2

Reaction notes

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