Hydrochloric Acid → 4-Methyl-2-{2-[1-(tetrahydro-pyran-2-yl)-1H-indazol-4-yl]-acetylamino}-thiazole-5-carboxylic acid

HRID 1952555Notes

Reaction equation

HRID 1952555 reaction equation
C([O:3][C:4]([C:6]1[S:10][C:9]([NH:11][C:12](=[O:29])[CH2:13][C:14]2[CH:22]=[CH:21][CH:20]=[C:19]3[C:15]=2[CH:16]=[N:17][N:18]3[CH:23]2[CH2:28][CH2:27][CH2:26][CH2:25][O:24]2)=[N:8][C:7]=1[CH3:30])=[O:5])C.O.[OH-].[Li+].C(O)C.Cl>O.[Cl-].[Na+]>[CH3:30][C:7]1[N:8]=[C:9]([NH:11][C:12](=[O:29])[CH2:13][C:14]2[CH:22]=[CH:21][CH:20]=[C:19]3[C:15]=2[CH:16]=[N:17][N:18]3[CH:23]2[CH2:28][CH2:27][CH2:26][CH2:25][O:24]2)[S:10][C:6]=1[C:4]([OH:5])=[O:3]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 702EthanolHCID 168937Lithium hydroxide, monohydrateHCID 86671253HCID 86671253, compound

Product 1

HCID 866712544-Methyl-2-{2-[1-(tetrahydro-pyran-2-yl)-1H-indazol-4-yl]-acetylamino}-thiazole-5-carboxylic acidYield 72.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 5234Sodium ChlorideSolvent

Procedure

A mixture of 4-Methyl-2-{2-[1-(tetrahydro-pyran-2-yl)-1H-indazol-4-yl]-acetylamino}-thiazole-5-carboxylic acid ethyl ester (800 mg, 1.867 mmol), lithium hydroxide monohydrate (394 mg, 9.391 mmol), ethanol (8 mL) and water (24 mL) was placed in an oil bath preheated to 90° C. and the resulting solution was heated for 28 min. The reaction solution was diluted with water (20 mL), saturated with sodium chloride, acidified with aqueous 2N HCl and extracted with 4/1 ethyl acetate/THF (4×100 mL). The organic layers were combined, washed with brine (50 mL), dried over MgSO4, filtered and concentrated under reduced pressure to give 4-Methyl-2-{2-[1-(tetrahydro-pyran-2-yl)-1H-indazol-4-yl]-acetylamino}-thiazole-5-carboxylic acid (0.54 g, 72.2%) as a yellow solid. MS m/e 401.4 (M+H+).

Workup

  1. customwas placed in an oil bath
  2. custompreheated to 90° C.
  3. temperaturethe resulting solution was heated for 28 min
  4. extractionextracted with 4/1 ethyl acetate/THF (4×100 mL)
  5. washwashed with brine (50 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-102d46d895da4909a1243b10fc9fae9f
Source dataset
uspto-grants-2013_03
Patent number
US08404859B2

Reaction notes

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