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

HRID 1410047Notes

Reaction equation

HRID 1410047 reaction equation
[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([NH:11][C:12]2[C:13]3[N:30]=[CH:29][S:28][C:14]=3[N:15]=[C:16]([C:18]3[CH:19]=[C:20]([CH:25]=[CH:26][CH:27]=3)[C:21]([O:23]C)=[O:22])[N:17]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[OH-].[Na+].Cl>O1CCOCC1.O>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([NH:11][C:12]2[C:13]3[N:30]=[CH:29][S:28][C:14]=3[N:15]=[C:16]([C:18]3[CH:19]=[C:20]([CH:25]=[CH:26][CH:27]=3)[C:21]([OH:23])=[O:22])[N:17]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:3])=[O:4]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 66549139Methyl 3-(7-(3-(methylsulfonyl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoate

Product 1

HCID 665491403-(7-(3-(Methylsulfonyl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoic acidYield 40.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

Methyl 3-(7-(3-(methylsulfonyl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoate (130 mg, 0.29 mmol) and NaOH (130 mg, 3.25 mmol) in 3 mL of 1,4-dioxane and 3 mL of H2O were stirred at room temperature for 3 hours and then treated by conc. HCl until pH=3-4. The solvent was removed under reduce pressure the residue was purified by preparative HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 ml/inj, flow rate: 20 ml/min; wavelength: 214 nm and 254 nm; the gradient conditions are: 40% acetonitrile/60% water (0.1% TFA V/V) initially, and then proceed to 55% acetonitrile/45% water (0.1% TFA V/V) in a linear fashion after just 9 min.) to give 3-(7-(3-(methylsulfonyl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoic acid (50 mg, 40%) as a yellow solid. 1H NMR (300 MHz, DMSO): δ 13.18 (brs, 1H), 10.76 (s, 1H), 9.45 (s, 1H), 8.99-8.95 (m, 2H), 8.72 (dt, 1H, J1=7.8 Hz, J2=1.5 Hz), 8.22-8.18 (m, 1H), 8.08 (dt, 1H, J2=8.1 Hz, J2=1.4 Hz), 7.69-7.61 (m, 3H), 3.24 (s, 3H). LC-MS: 427 [M+H]+, tR=1.48 min. HPLC: 98.42% at 214 nm, 99.23% at 254 nm, tR=5.75 min.

Workup

  1. customThe solvent was removed
  2. customwas purified by preparative HPLC (Gemini 5u C18 150×21.2 mm

Sources & evidence

ORD record
ord-22d21fd104e64974a67049e98855b90b
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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