Sodium Hydroxide → 4-(3-(8-(5,6-Dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzamido)-2-methoxybenzoic acid

HRID 1755374Notes

Reaction equation

HRID 1755374 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([NH:11][C:12]2[C:13]3[N:14]([CH:39]=[CH:40][N:41]=3)[N:15]=[C:16]([C:18]3[CH:19]=[C:20]([CH:36]=[CH:37][CH:38]=3)[C:21]([NH:23][C:24]3[CH:33]=[CH:32][C:27]([C:28]([O:30]C)=[O:29])=[C:26]([O:34][CH3:35])[CH:25]=3)=[O:22])[CH:17]=2)=[N:7][C:8]=1[O:9][CH3:10].[OH-].[Na+]>O1CCOCC1.O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([NH:11][C:12]2[C:13]3[N:14]([CH:39]=[CH:40][N:41]=3)[N:15]=[C:16]([C:18]3[CH:19]=[C:20]([CH:36]=[CH:37][CH:38]=3)[C:21]([NH:23][C:24]3[CH:33]=[CH:32][C:27]([C:28]([OH:30])=[O:29])=[C:26]([O:34][CH3:35])[CH:25]=3)=[O:22])[CH:17]=2)=[N:7][C:8]=1[O:9][CH3:10]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 86682729Methyl 4-(3-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzamido)-2-methoxybenzoate

Product 1

HCID 715261724-(3-(8-(5,6-Dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzamido)-2-methoxybenzoic acidYield 25%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of methyl 4-(3-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzamido)-2-methoxybenzoate (100 mg, 0.18 mmol) and NaOH (100 mg, 2.5 mmol) in 1,4-dioxane (5 mL) and water (5 mL) was stirred for 2 h at 50° C. The mixture was concentrated and adjusted to pH=2 with 3M HCl. The precipitate was filtered and the solid was washed with MeOH (1 mL) and dichloromethane (1 mL) to give 4-(3-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzamido)-2-methoxybenzoic acid (24 mg, 25%) as a brown solid. 1H NMR (300 MHz, DMSO): δ 10.62 (s, 1H), 10.01 (s, 1H), 8.63 (s, 1H), 8.53 (s, 1H), 8.26-8.21 (m, 2H), 8.09 (d, 1H, J=7.5 Hz), 7.75-7.67 (m, 4 h), 7.50 (dd, 1H, J1=8.4 Hz, J2=1.8 Hz), 7.41 (d, 1H, J=8.4 Hz), 7.10 (d, 1H, J=8.4 Hz), 4.03 (s, 3H), 3.84 (s, 3H), 3.77 (s, 3H). LC-MS: [M+H]+, 541, tR=1.548 min, HPLC: 95.24% at 214 nm, 95.03% at 254 nm, tR=7.943 min.

Workup

  1. concentrationThe mixture was concentrated
  2. filtrationThe precipitate was filtered
  3. washthe solid was washed with MeOH (1 mL) and dichloromethane (1 mL)

Sources & evidence

ORD record
ord-1830e84244444a17b7e3c484ef078275
Source dataset
uspto-grants-2015_10
Patent number
US09169259B2

Reaction notes

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