Hydrochloric Acid → 3-(7-(3-(Trifluoromethyl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoic acid

HRID 1410105Notes

Reaction equation

HRID 1410105 reaction equation
[F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([NH:9][C:10]2[C:11]3[N:28]=[CH:27][S:26][C:12]=3[N:13]=[C:14]([C:16]3[CH:17]=[C:18]([CH:23]=[CH:24][CH:25]=3)[C:19]([O:21]C)=[O:20])[N:15]=2)[CH:6]=[CH:7][CH:8]=1.[OH-].[Na+].Cl>C1COCC1.CO.O>[F:30][C:2]([F:1])([F:29])[C:3]1[CH:4]=[C:5]([NH:9][C:10]2[C:11]3[N:28]=[CH:27][S:26][C:12]=3[N:13]=[C:14]([C:16]3[CH:17]=[C:18]([CH:23]=[CH:24][CH:25]=3)[C:19]([OH:21])=[O:20])[N:15]=2)[CH:6]=[CH:7][CH:8]=1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 66550340Methyl 3-(7-(3-(trifluoromethyl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoate

Product 1

HCID 665503413-(7-(3-(Trifluoromethyl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoic acidYield 67.9%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of methyl 3-(7-(3-(trifluoromethyl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoate (100 mg, 0.23 mmol) in 3 mL of THF and 3 mL of methanol was added a solution of sodium hydroxide (46.5 mg, 1.16 mmol) in 1 mL of water at room temperature. Then the reaction mixture was stirred at room temperature for 16 hours. HCl was added until pH=4. The solvent was evaporated at 40° C. at reduced pressure and the residue was purified by silica gel chromatography (silica gel 200-300 mesh, eluting with a mixture of petroleum ether and ethyl acetate (1:1)) to give 3-(7-(3-(trifluoromethyl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoic acid (65 mg, 67.2%) as a pale yellow solid. 1H NMR (300 MHz, DMSO): δ 13.15 (brs, 1H), 10.65 (s, 1H), 9.46 (s, 1H), 9.00 (s, 1H), 8.67 (s, 1H), 8.60 (d, 1H, J=7.8 Hz), 8.26 (d, 1H, J=7.8 Hz), 8.10 (d, 1H, J=7.5 Hz), 7.68-7.63 (m, 2H), 7.49 (d, 1H, J=7.8 Hz). LC-MS: 417 [M+H]+, 415 [M−H]−, tR=1.65 min. HPLC: 95.14% at 214 nm, 95.28% at 254 nm, tR=7.71 min.

Workup

  1. customThe solvent was evaporated at 40° C. at reduced pressure
  2. customthe residue was purified by silica gel chromatography (silica gel 200-300 mesh
  3. washeluting with a mixture of petroleum ether and ethyl acetate (1:1))

Sources & evidence

ORD record
ord-38d227725a2b4fd6b009b1f7fd78c80b
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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