Hydrochloric Acid → Racemic 4-(5-{3-[(5-fluoro-4-methylpyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)-4-hydroxy-2,2-dimethylcyclohexanecarboxylic acid

HRID 1040152Notes

Reaction equation

HRID 1040152 reaction equation
[F:1][C:2]1[C:3]([CH3:34])=[N:4][C:5]([NH:8][C:9]2[CH:10]=[C:11]([C:16]3[S:20][C:19]([C@@:21]4([OH:33])[CH2:26][CH2:25][C@H:24]([C:27]([O:29]C)=[O:28])[C:23]([CH3:32])([CH3:31])[CH2:22]4)=[N:18][CH:17]=3)[CH:12]=[C:13]([CH3:15])[CH:14]=2)=[N:6][CH:7]=1.[OH-].[Na+].Cl>CO>[F:1][C:2]1[C:3]([CH3:34])=[N:4][C:5]([NH:8][C:9]2[CH:10]=[C:11]([C:16]3[S:20][C:19]([C:21]4([OH:33])[CH2:26][CH2:25][CH:24]([C:27]([OH:29])=[O:28])[C:23]([CH3:31])([CH3:32])[CH2:22]4)=[N:18][CH:17]=3)[CH:12]=[C:13]([CH3:15])[CH:14]=2)=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 67430268racemic methyl(1S,4R)-4-(5-{3-[(5-fluoro-4-methylpyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)-4-hydroxy-2,2-dimethylcyclohexanecarboxylate

Product 1

HCID 67248815Racemic 4-(5-{3-[(5-fluoro-4-methylpyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)-4-hydroxy-2,2-dimethylcyclohexanecarboxylic acidYield 85.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of racemic methyl(1S,4R)-4-(5-{3-[(5-fluoro-4-methylpyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)-4-hydroxy-2,2-dimethylcyclohexanecarboxylate (70 mg, 0.14 mmol) in Methanol (1 mL) was added sodium hydroxide (1M, 0.87 ml, 0.87 mmol). The resulting suspension was heated to 110° C. for 10 min under microwave irradiation. The reaction was cooled to ambient temperature, and the pH was adjusted to a range of 3-4 (pH paper) using HCl (1 N in water). The resulting mixture was extracted with 10% IPA:CHCl3 (3×). The combined organic layers were dried over Na2SO4 and concentrated in vacuo to provide racemic 4-(5-{3-[(5-fluoro-4-methylpyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)-4-hydroxy-2,2-dimethylcyclohexanecarboxylic acid (58 mg, 0.12 mmol, 58% yield). The racemate was subjected to purification by chiral supercritical fluid chromatography (35%/65% Methanol/CO2, with a flow rate of 70 mL/min and a 4 minute run time).

Workup

  1. temperatureThe reaction was cooled to ambient temperature
  2. extractionThe resulting mixture was extracted with 10% IPA
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d50ac249467044d882b614a18e8029a4
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

Loading…