Hydrochloric Acid → HCID 68379143, compound

HRID 1410057Notes

Reaction equation

HRID 1410057 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][C:12]2[C:13]3[N:39]=[CH:38][S:37][C:14]=3[N:15]=[C:16]([C:18]3[CH:19]=[C:20](/[C:24](/[F:36])=[CH:25]/[C:26]4[CH:35]=[CH:34][C:29]([C:30]([O:32]C)=[O:31])=[CH:28][CH:27]=4)[CH:21]=[CH:22][CH:23]=3)[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[OH-].[Na+].Cl>O1CCOCC1.O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][C:12]2[C:13]3[N:39]=[CH:38][S:37][C:14]=3[N:15]=[C:16]([C:18]3[CH:19]=[C:20](/[C:24](/[F:36])=[CH:25]/[C:26]4[CH:35]=[CH:34][C:29]([C:30]([OH:32])=[O:31])=[CH:28][CH:27]=4)[CH:21]=[CH:22][CH:23]=3)[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 68379225HCID 68379225, compound

Product 1

HCID 68379143HCID 68379143, compoundYield 52.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a stirred solution of (Z)-methyl 4-(2-(3-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)phenyl)-2-fluorovinyl)benzoate (50 mg, 0.09 mmol) in 3 mL of 1,4-dioxane and 3 mL of H2O was added NaOH (140 mg, 3.5 mmol) at room temperature. Then the reaction was stirred at room temperature overnight 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 (Z)-4-(2-(3-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)phenyl)-2-fluorovinyl)benzoic acid (25 mg, 51%) as a yellow solid. 1H NMR (300 MHz, DMSO): δ 12.94 (brs, 1H, exchangeable by D2O), 10.18 (s, 1H, exchangeable by D2O), 9.40 (s, 1H), 8.54-8.49 (m, 2H), 7.82-7.74 (m, 3H), 7.41-7.31 (m, 5H), 6.90-6.78 (m, 2H), 3.80 (s, 6H). LC-MS: 529 [M+H]+, 527 [M−H]−, tR=1.71 min. HPLC: 96.85% at 214 nm, 95.49% at 254 nm, tR=5.08 min.

Workup

  1. customThe solvent was removed
  2. customwas purified by preparative HPLC (Gemini 5u C18 150×21.2 mm
  3. wait40% 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.

Sources & evidence

ORD record
ord-5d084c52262443d19d57043d34781707
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

Loading…