Hydrochloric Acid → 3-(7-(3-(2-(Methoxymethyl)pyrrolidin-1-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoic acid hydrochloride

HRID 1410052Notes

Reaction equation

HRID 1410052 reaction equation
[CH3:1][O:2][CH2:3][CH:4]1[CH2:8][CH2:7][CH2:6][N:5]1[C:9]1[CH:10]=[C:11]([NH:15][C:16]2[C:17]3[N:34]=[CH:33][S:32][C:18]=3[N:19]=[C:20]([C:22]3[CH:23]=[C:24]([CH:29]=[CH:30][CH:31]=3)[C:25]([O:27]C)=[O:26])[N:21]=2)[CH:12]=[CH:13][CH:14]=1.[OH-].[Na+].[ClH:37]>O1CCOCC1.O>[ClH:37].[CH3:1][O:2][CH2:3][CH:4]1[CH2:8][CH2:7][CH2:6][N:5]1[C:9]1[CH:10]=[C:11]([NH:15][C:16]2[C:17]3[N:34]=[CH:33][S:32][C:18]=3[N:19]=[C:20]([C:22]3[CH:23]=[C:24]([CH:29]=[CH:30][CH:31]=3)[C:25]([OH:27])=[O:26])[N:21]=2)[CH:12]=[CH:13][CH:14]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 68379311Methyl 3-(7-(3-(2-(methoxymethyl)pyrrolidin-1-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoate

Product 1

HCID 683792103-(7-(3-(2-(Methoxymethyl)pyrrolidin-1-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoic acid hydrochlorideYield 31%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

Methyl 3-(7-(3-(2-(methoxymethyl)pyrrolidin-1-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoate (100 mg, 0.21 mmol) and NaOH (100 mg, 2.5 mmol) in 3 mL of 1,4-dioxane and 3 mL of H2O was 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: 50% acetonitrile/50% water (0.1% TFA V/V) initially, and then proceed to 80% acetonitrile/20% water (0.1% TFA V/V) in a linear fashion after just 9 min.) to give 3-(7-(3-(2-(methoxymethyl)pyrrolidin-1-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoic acid hydrochloride (30 mg, 31%) as a yellow solid. 1H NMR (300 MHz, DMSO): δ 10.28 (s, 1H), 9.41 (s, 1H), 8.98 (s, 1H), 6.62 (d, 1H, J=7.5 Hz), 8.08 (d, 1H, J=7.5 Hz), 7.66-7.62 (m, 2H), 7.47 (brs, 1H), 7.28 (brs, 1H), 3.95 (brs, 1H), 3.54-3.51 (m, 2H), 3.32-3.27 (m, 2H), 3.19 (s, 3H), 2.03-1.19 (m, 4H). LC-MS: 462 [M+H]+, tR=1.66 min. HPLC: 96.12% at 214 nm, 96.76% at 254 nm, tR=6.84 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-3032a155e26e4000a253f0650099a1e7
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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