Sodium Hydroxide → 3-(8-(6-(2-Methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acid

HRID 1755302Notes

Reaction equation

HRID 1755302 reaction equation
[CH3:1][CH:2]1[CH2:6][CH2:5][CH2:4][N:3]1[C:7]1[N:12]=[C:11]([NH:13][C:14]2[C:15]3[N:16]([CH:30]=[CH:31][N:32]=3)[N:17]=[C:18]([C:20]3[CH:21]=[C:22]([CH:27]=[CH:28][CH:29]=3)[C:23]([O:25]C)=[O:24])[CH:19]=2)[CH:10]=[CH:9][CH:8]=1.[OH-].[Na+]>O1CCOCC1.O>[CH3:1][CH:2]1[CH2:6][CH2:5][CH2:4][N:3]1[C:7]1[N:12]=[C:11]([NH:13][C:14]2[C:15]3[N:16]([CH:30]=[CH:31][N:32]=3)[N:17]=[C:18]([C:20]3[CH:21]=[C:22]([CH:27]=[CH:28][CH:29]=3)[C:23]([OH:25])=[O:24])[CH:19]=2)[CH:10]=[CH:9][CH:8]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 71525521Methyl 3-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoate

Product 1

HCID 715255203-(8-(6-(2-Methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acidYield 78.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of methyl 3-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoate (210 mg, 0.49 mmol) in dioxane (10 mL) and water (10 mL) was added NaOH (150 mg, 3.75 mmol), The mixture was heated to 40° C. with stirring for 2 h. The solution was concentrated in vacuo, washed with dichloromethane (10 mL×3), then additional water (10 mL) was added and this solution was adjusted to pH=4 by addition of concentrated HCl. The solid formed was filtered to give 3-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acid (0.160 g, 78%) as a light yellow solid. 1H NMR (300 MHz, DMSO): δ 13.25 (s, 1H), 9.74 (s, 1H), 8.85 (s, 1H), 8.50 (s, 1H), 8.26-8.08 (m, 3H), 7.72-7.67 (m, 2H), 7.53-7.44 (m, 1H), 6.75 (d, 1H, J=7.8 Hz), 6.09 (d, 1H, J=8.1 Hz), 4.25-4.21 (m, 1H), 3.62-3.57 (m, 1H), 2.13-1.98 (m, 3H), 1.70-1.68 (m, 2H), 1.12 (d, 3H, J=6.0 Hz). LC-MS: [M+H]+, 415, tR=1.68 min, HPLC: 98.2% at 214 nm, 98.37% at 254 nm, tR=6.21 min.

Workup

  1. concentrationThe solution was concentrated in vacuo
  2. washwashed with dichloromethane (10 mL×3)
  3. additionadditional water (10 mL) was added
  4. additionthis solution was adjusted to pH=4 by addition of concentrated HCl
  5. customThe solid formed
  6. filtrationwas filtered

Sources & evidence

ORD record
ord-68f33238c5ef46c191f86c9ff2ce0c3c
Source dataset
uspto-grants-2015_10
Patent number
US09169259B2

Reaction notes

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