Hydrochloric Acid → 3-(4-(3-methyl-5-(pyrimidin-2-ylamino)phenyl)-1H-pyrazol-1-yl)cyclobutanecarboxylic acid

HRID 595323Notes

Reaction equation

HRID 595323 reaction equation
[OH-].[Na+].[CH3:3][C:4]1[CH:5]=[C:6]([C:17]2[CH:18]=[N:19][N:20]([CH:22]3[CH2:25][CH:24]([C:26]([O:28]C)=[O:27])[CH2:23]3)[CH:21]=2)[CH:7]=[C:8]([NH:10][C:11]2[N:16]=[CH:15][CH:14]=[CH:13][N:12]=2)[CH:9]=1.Cl>CO.O.C(OCC)(=O)C.[Cl-].[Na+].O>[CH3:3][C:4]1[CH:5]=[C:6]([C:17]2[CH:18]=[N:19][N:20]([CH:22]3[CH2:23][CH:24]([C:26]([OH:28])=[O:27])[CH2:25]3)[CH:21]=2)[CH:7]=[C:8]([NH:10][C:11]2[N:16]=[CH:15][CH:14]=[CH:13][N:12]=2)[CH:9]=1

Participants

8

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 118208777methyl 3-(4-(3-methyl-5-(pyrimidin-2-ylamino)phenyl)-1H-pyrazol-1-yl)cyclobutanecarboxylate

Product 1

HCID 1182088123-(4-(3-methyl-5-(pyrimidin-2-ylamino)phenyl)-1H-pyrazol-1-yl)cyclobutanecarboxylic acid

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
50 °C

Procedure

Sodium hydroxide (1.0 M in water, 1.68 mL, 1.68 mmol) was added to a solution of methyl 3-(4-(3-methyl-5-(pyrimidin-2-ylamino)phenyl)-1H-pyrazol-1-yl)cyclobutanecarboxylate (Isomer 1) (203 mg, 0.559 mmol) in methanol (4.0 mL) and water (1.0 mL). The reaction mixture was heated to 50° C. and stirred for 1 hour. The reaction mixture was cooled to ambient temperature and diluted with hydrochloric acid (1.0 M in water, 1.68 mL, 1.68 mmol) while stirring. The resulting suspension was diluted with ethyl acetate (100 mL) and brine (10 mL). The organic layer was separated, washed with brine (10 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to afford 3-(4-(3-methyl-5-(pyrimidin-2-ylamino)phenyl)-1H-pyrazol-1-yl)cyclobutanecarboxylic acid (Isomer 1). The material was used without purification in the subsequent step. MS ESI calc'd. for C19H20N5O2 [M+H]+ 350. found 350.

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. stirringwhile stirring
  3. customThe organic layer was separated
  4. washwashed with brine (10 mL)
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-281ffa26c11e4ac58db6e7ab2360fb43
Source dataset
uspto-grants-2016_01
Patent number
US09242984B2

Reaction notes

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