Hydrochloric Acid → HCID 66763514, compound

HRID 2188981Notes

Reaction equation

HRID 2188981 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]([C:17](=[O:20])[NH:18][CH3:19])=[C:15]3[N:10]([N:11]=[CH:12][C:13]([C:21]4[C:22]([CH3:33])=[CH:23][C:24]([O:31][CH3:32])=[C:25]([CH:30]=4)[C:26]([O:28]C)=[O:27])=[CH:14]3)[N:9]=2)=[CH:4][CH:3]=1.[OH-].[Na+].Cl>O1CCOCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]([C:17](=[O:20])[NH:18][CH3:19])=[C:15]3[N:10]([N:11]=[CH:12][C:13]([C:21]4[C:22]([CH3:33])=[CH:23][C:24]([O:31][CH3:32])=[C:25]([CH:30]=4)[C:26]([OH:28])=[O:27])=[CH:14]3)[N:9]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 66763663Methyl 5-(2-(4-fluorophenyl)-3-(methylcarbamoyl)pyrazolo[1,5-b]pyridazin-5-yl)-2-methoxy-4-methylbenzoate

Product 1

HCID 66763514HCID 66763514, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution containing methyl 5-(2-(4-fluorophenyl)-3-(methylcarbamoyl)pyrazolo[1,5-b]pyridazin-5-yl)-2-methoxy-4-methylbenzoate (0.061 g, 0.14 mmol) and dioxane (0.7 mL) was added aqueous sodium hydroxide (0.7 mL, 2.0 M). The mixture was stirred at room temperature for 2 h. The solution was adjusted to below pH 4 with aqueous HCl (1.5 mL, 1.0 N). 5-(2-(4-fluorophenyl)-3-(methylcarbamoyl)pyrazolo[1,5-b]pyridazin-5-yl)-2-methoxy-4-methylbenzoic acid precipitated as a tan solid. It was filtered off, washed with water (3×4 mL) and air dried. 1H NMR (400 MHz, CHLOROFORM-d) δ 8.66 (d, J=2.5 Hz, 1H), 8.38 (d, J=2.5 Hz, 1H), 8.16 (s, 1H), 7.83-7.73 (m, 2H), 7.29-7.22 (m, 2H), 7.05 (s, 1H), 5.68 (br. s., 1H), 4.17 (s, 3H), 2.89 (d, J=5.0 Hz, 3H), 2.48 (s, 3H). LCMS retention time: 3.508 min. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna, 3 micron, C18, 2.0×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 0.8 mL/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 4 min, a hold time of 1 min, and an analysis time of 5 min where solvent A was 10% methanol/90% H2O/10 mM TFA and solvent B was 10% H2O/90% methanol/10 mM TFA. MS data was determined using a Micromass Platform for LC in electrospray mode. m/z 435 (MH+).

Workup

  1. custom5-(2-(4-fluorophenyl)-3-(methylcarbamoyl)pyrazolo[1,5-b]pyridazin-5-yl)-2-methoxy-4-methylbenzoic acid precipitated as a tan solid
  2. filtrationIt was filtered off
  3. washwashed with water (3×4 mL) and air
  4. customdried
  5. customequipped with a Phenomenex-Luna, 3 micron, C18, 2.0×50 mm column
  6. washThe elution conditions
  7. customa gradient time of 4 min
  8. customa hold time of 1 min
  9. customan analysis time of 5 min where solvent A was 10% methanol/90% H2O/10 mM TFA and solvent B

Sources & evidence

ORD record
ord-1b19a364efd1483aa9472907fa3b4ad2
Source dataset
uspto-grants-2012_12
Patent number
US08324212B2

Reaction notes

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